Developmental Biology

Visit the Aronow-Jegga Lab.

Biography

Dr. Aronow is a computational geneticist and developmental biologist. His group carries out analyses of many different kinds of data, develops algorithms, and builds websites and databases. These tools allow researchers from varying disciplines and backgrounds to analyze genetic and genomic data—either their own or that gathered from published sources—to better understand, model, and carry out new research about normal development and disease. His group is highly collaborative with clinical and basic researchers across a broad range of research projects encompassing many areas of biology and disease, including normal and abnormal development, in vivo and in vitro disease models, and large-scale clinical studies.

Data of interest includes genetic, genomic, proteomic, metabolomic, imaging, and therapeutic agent response measures. Recent areas of interest include large-scale clinical sample analyses, single cell-based dissection of developmental and disease tissues, and in vitro stem cell-based modeling of normal and disease-affected tissues including abnormal neurological, immunological, cardiac, and cancer tissues.

The lab’s recent efforts focus on predicting new therapeutic approaches based on disease mechanisms in the areas of inflammatory bowel disease, eosinophilic esophagitis, sickle cell anemia, cardiac development, and neurological and psychiatric diseases. His group is working on efforts to define the transcriptome of the developing kidney, lung and brain. They are using stem cell-derived cells and organoids to dissect mechanisms that underlie organ development and function as well as oncogenesis. They are also working to infer novel disease indications for known drugs by semantically linking drug action and disease mechanism relationships.

BS: Chemistry, Stanford University, Stanford, CA, 1976.

PhD: Biochemistry, University of Kentucky, Lexington, KY, 1986.

Research Fellowship: Division of Basic Science Research, Cincinnati Children's Research Foundation, Cincinnati, OH, 1986-1989.

View Publications on Google Scholar

Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, Grimes HL. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature. 2016 Aug 31;537(7622):698-702.

Bakeer N, James J, Roy S, Wansapura J, Shanmukhappa SK, Lorenz JN, Osinska H, Backer K, Huby AC, Shrestha A, Niss O, Fleck R, Quinn CT, Taylor MD, Purevjav E, Aronow BJ, Towbin JA, Malik P. Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology. Proc Natl Acad Sci U S A. 2016 Aug30;113(35):E5182-91.

Kanisicak O, Khalil H, Ivey MJ, Karch J, Maliken BD, Correll RN, Brody MJ, J Lin SC, Aronow BJ, Tallquist MD, Molkentin JD. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun. 2016 Jul 22;7:12260.

Sarangdhar M, Tabar S, Schmidt C, Kushwaha A, Shah K, Dahlquist JE, Jegga AG, Aronow BJ. Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data. Nat Biotechnol. 2016 Jul 12;34(7):697-700.

Salomonis N, Dexheimer PJ, Omberg L, Schroll R, Bush S, Huo J, Schriml L, Ho Sui S, Keddache M, Mayhew C, Shanmukhappa SK, Wells J, Daily K, Hubler S, Wang Y, Zambidis E, Margolin A, Hide W, Hatzopoulos AK, Malik P, Cancelas JA, Aronow BJ, Lutzko C. Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium. Stem Cell Reports. 2016 Jul 12;7(1):110-25.

Samantha A. Brugmann, PhD Member, Division of Plastic Surgery

Samantha A. Brugmann, PhD, is a developmental biologist who aims to understand craniofacial development and elucidate the molecular basis for diseases that affect the craniofacial complex. Furthermore, Dr. Brugmann attempts to understand the forces that help pattern the face during normal and abnormal development she utilizes various model systems with unique facial morphologies.

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513-636-1599 samantha.brugmann@cchmc.org

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Samantha A. Brugmann, PhD

Member, Division of Plastic Surgery

Academic Affiliations

Associate Professor, UC Department of Surgery

Phone 513-636-1599

Email samantha.brugmann@cchmc.org

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Craniofacial development

Visit the Brugmann Lab.

Biography

Samantha A. Brugmann, PhD, is an associate professor of pediatrics in the Divisions of Plastic Surgery and Developmental Biology within the University of Cincinnati College of Medicine. She received her BS in cell and molecular biology from Tulane University in New Orleans, LA. She then obtained her PhD in genetics from George Washington University in Washington, DC where she studied cranial sensory placode development in Xenopus laevis. She performed her postdoctoral fellowship at Stanford University where her research focused on craniofacial development. While at Stanford she received a Ruth L. Kirschstein National Research Service Awards for Individual Postdoctoral Fellows (F32), a Pediatric Research Fund-Child Health Research Program Grant and a NIH Pathway to Independence Award (K99/R00). She joined Cincinnati Children’s Hospital Medical Center in January 2011 to study craniofacial development and disease.

BS: Tulane University, New Orleans, LA.

PhD: George Washington University, Washington DC.

Fellowship: Stanford University, Stanford, CA.

Chang CF, Schock EN, Attia A, Stottmann RW, Brugmann SA. The ciliary baton: orchestrating neural crest development. Current Topics in Developmental Biology. In press.

Brugmann SA, Wells JM. Building additional complexity to in vitro-derived intestinal tissues. Stem Cell Res Ther. 2013;4 Suppl 1:S1.

Liu H, Lan Y, Xu , Chang CF, Brugmann SA, Jiang R. Odd-skipped related-1 controls neural crest chondrogenesis during tongue development. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18555-60.

Chang CF, Schock EN, O’Hare EA, Dodgson J, Cheng HH, Muir WM, Edelmann RE, Delany ME, Brugmann SA. The cellular and molecular etiology of the craniofacial defects in the avian ciliopathic mutant, talpid2. Development. 2014 Aug;141(15):3003-12.

Rada-Iglesias A, Bajpai R, Prescott S, Brugmann SA, Swigut T, Wysocka J. Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest. Cell Stem Cell. 2012 Nov 2;11(5):633-48.

Lenton K, James AW, Manu A, Brugmann SA, Birker D, Nelson ER, Leucht P, Helms JA, Longaker MT. Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. Genesis. 2011 Oct;49(10):784-96.

Powder KE, Ku YC, Brugmann SA, Veile RA, Renaud NA, Helms JA, Lovett M. A cross-species analysis of microRNAs in the developing avian face. PLoS One. 2012;7(4):e35111.

Kenneth J. Campbell, PhD

Kenneth J. Campbell, PhD, studies the molecular genetic control of mouse forebrain development with a particular focus on the generation of neuronal diversity in the ventral telencephalon.

513-636-0246 kenneth.campbell@cchmc.org

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Kenneth J. Campbell, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-0246

Fax 513-636-4317

Email kenneth.campbell@cchmc.org

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Molecular genetic control of mammalian forebrain development

MS: University of Toronto, Toronto, Canada, 1990.

PhD: University of Lund, Lund, Sweden, 1994.

Postdoctoral Fellow: Skirball Institute, NYU Med Center, 1995-97.

Waclaw RR, Wang B, Pei Z, Ehrman LA, Campbell K. Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates. Neuron. 2009;63:451-65.

Wang B, Waclaw RR, Allen ZJ II, Guillemot F, Campbell K. Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon. Neural Development. 2009;4:5.

Waclaw RR, Allen Z, Bell SM, Erdelyi F, Szabo G, Potter SS, Campbell K. The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons. Neuron. 2006;49:503-16.

Campbell K. Cortical neuron specification: it has its time and place. Neuron. 2005;46:373-6.

Waclaw RR, Wang B, Campbell K. The homeobox gene Gsh2 is required for retinoid production in the embryonic mouse telencephalon. Development. 2004;131:4013-20.

Stenman J, Yu RT, Evans RM, Campbell K. Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the mouse telencephalon. Development. 2003;130:1113-22.

Stenman J, Toresson H, Campbell K. Identification of two distinct progenitor populations in the lateral ganglionic eminence: Implications for striatal and olfactory bulb neurogenesis. Journal of Neuroscience. 2003;23:167-74.

Cristina Cebrian, PhD

The kidneys originate in the embryo as the result of reciprocal inductive interactions between the ureteric bud epithelia and the metanephric mesenchyme. The ureteric bud branches repetitively in response to signals from the mesenchyme to give rise to the renal collecting system. Simultaneously, the mesenchyme aggregates around the ureteric bud tips and differentiates into the nephron epithelia. Over a dozen differentiated cell types arise from the seemingly homogeneous metanephric mesenchyme. The overarching goals of the Cebrian lab are to understand the cellular and molecular mechanisms that drive nephron differentiation during embryonic development, and to study the impact of developmental defects on kidney structure and function in the adult.

513-803-0470 cristina.cebrian@cchmc.org

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Cristina Cebrian, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-0470

Email cristina.cebrian@cchmc.org

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BSc: Universitat de Barcelona, Spain.

PhD: Universitat Autònoma de Barcelona, Spain.

Postdoctoral Fellow: Weill Cornell Medical College and Columbia University, New York, NY.

Combes AN, Wilson S, Phipson B, Binnie BB, Ju A, et al. Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number. Kidney Int. 2018 Mar;93(3):589-598.

Riccio P, Cebrian C, Zong H, Hippenmeyer S, Costantini F. Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis. PLoS Biol. 2016 Feb;14(2):e1002382.

Cebrian C, Asai N, D'Agati V, Costantini F. The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment. Cell Rep. 2014 Apr 10;7(1):127-37.

Packard A, Georgas K, Michos O, Riccio P, Cebrian C, et al. Luminal mitosis drives epithelial cell dispersal within the branching ureteric bud. Dev Cell. 2013 Nov 11;27(3):319-30.

Kuure S, Cebrian C, Machingo Q, Lu BC, Chi X, et al. Actin depolymerizing factors cofilin1 and destrin are required for ureteric bud branching morphogenesis. PLoS Genet. 2010 Oct 28;6(10):e1001176.

Michos O, Cebrian C, Hyink D, Grieshammer U, Williams L, et al. Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet. 2010 Jan 15;6(1):e1000809.

Lu BC, Cebrian C, Chi X, Kuure S, Kuo R, et al. Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nat Genet. 2009 Dec;41(12):1295-302.

Brenner-Anantharam A, Cebrian C, Guillaume R, Hurtado R, Sun TT, et al. Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling. Development. 2007 May;134(10):1967-75.

Grieshammer U, Cebrián C, Ilagan R, Meyers E, Herzlinger D, et al. FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development. 2005 Sep;132(17):3847-57.

Cebrián C, Borodo K, Charles N, Herzlinger DA. Morphometric index of the developing murine kidney. Dev Dyn. 2004 Nov;231(3):601-8.

Sang-Wook Cha, PhD

Sang-Wook Cha, PhD, investigates how Wnt/Planar Cell Polarity (PCP) signaling between lateral plate mesoderm (LPM) and endoderm regulates apicobasal polarity (ABP) of intestinal epithelium and controls radial-intercalation and gut elongation. Dr. Cha uses both amphibian and mouse/human organoids as the model systems.

513-803-3014 sang-wook.cha@cchmc.org

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Sang-Wook Cha, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-3014

Email sang-wook.cha@cchmc.org

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Molecular basis of fetal intestine development; Wnt signaling; stem cells

PhD: College of Medicine, Kyungpook National University, South Korea, 2005.

Senior Researcher: Brain Korea21 project, 2005-2007.

Research Fellow/Associate: Cincinnati Children’s Research Foundation, Cincinnati, OH, 2007-2012.

View PubMed Publications.

Cha SW, McAdams M, Kormish J, Wylie C, Kofron M. Foxi2 is an animally localized maternal mRNA in Xenopus, and an activator of the zygotic ectoderm activator Foxi1e. PLoS ONE. 2012;7(7):e41782.

Nandadasa S, Tao Q, Shoemaker A, Cha SW, Wylie C. Regulation of classical cadherin membrane expression and F-actin assembly by alpha-catenins, during Xenopus embryogenesis. PLoS ONE. 2012;7(6):e38756.

Cha SW, Tadjuidje E, Wylie C, Heasman J. The roles of maternal Vangl2 and aPKC in Xenopus oocyte and embryo patterning. Development. 2011 Sep;138(18):3989-4000.

Tadjuidje E, Cha SW, Louza M, Wylie C, Heasman J. The functions of maternal Dishevelled 2 and 3 in the Early Xenopus embryo. Dev Dyn. 2011 Jul;240(7):1727-36.

Blythe SA, Cha SW, Tadjuidje E, Heasman J, Klein PS. beta-Catenin primes organizer gene expression by recruiting a histone H3 arginine 8 methyltransferase, Prmt2. Dev Cell. 2010 Aug 17;19(2):220-31.

Cha SW, Heasman J. Using oocytes for Wnt signaling assays: paracrine assays and Wnt-conditioned medium: review. Methods. 2010 May;51(1):52-5.

Cha SW, Tadjuidje E, White J, Wells J, Mayhew C, Wylie C, Heasman J. Wnt11/5a complex formation caused by tyrosine sulfation increases canonical signaling activity. Curr Biol. 2009 Sep 29;19(18):1573-80.

Roger Cornwall, MD Pediatric Hand Surgeon

Roger Cornwall, MD, investigates the neurological control of postnatal muscle growth and development. The goal of his research is to identify novel physiological treatments for pediatric neuromuscular contractures.

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513-636-7319 roger.cornwall@cchmc.org

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Roger Cornwall, MD

Pediatric Hand Surgeon

Clinical Director, Division of Pediatric Orthopaedics

Director, Hand and Upper Extremity Surgery Fellowship

Surgical Director, Epidermolysis Bullosa Center

Academic Affiliations

Associate Professor, UC Department of Orthopedic Surgery

Phone 513-636-7319

Fax 513-636-3928

Email roger.cornwall@cchmc.org

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Clinical

Brachial plexus birth palsy; pediatric hand and wrist trauma; congenital hand and upper extremity abnormalities; complex pediatric elbow trauma and deformities; gymnast wrist.

Research

Brachial plexus injury and the growth and development of muscles; minimally invasive surgical treatment for shoulder contracture in brachial plexus birth palsy; nerve transfers for unreconstructable brachial plexus birth injuries; outcomes following surgical and nonsurgical treatment algorithms for pediatric hand fractures; outcomes of non-operative and operative treatment algorithms for chronic adolescent wrist pain.

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Biography

Dr. Cornwall is a full time pediatric hand and upper extremity surgeon who founded the Hand and Upper Extremity Center at Cincinnati Children's Hospital Medical Center in 2009. He is nationally known for his expertise in treating conditions that affect the pediatric hand and upper extremities, including complex trauma and congenital deformities, and brachial plexus injuries. He also runs a basic science laboratory investigating the neurological control of postnatal muscle growth, aiming to develop novel physiological treatments for neuromuscular contractures.

MD: Columbia University, New York, NY, 1997.

Residency: Orthopaedic Surgery, Mount Sinai Hospital, New York, NY, 2002.

Fellowship: Hand and Upper Extremity Surgery, Harvard University, Brigham and Women's Hospital, Massachusetts General Hospital, Children's Hospital Boston, Boston, MA, 2003.

Fellowship: Pediatric Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, 2004.

Visiting Fellowship: Pediatric Orthopaedic and Hand Surgery, Groote Schuur Hospital and Red Cross Children's Hospital, Cape Town, South Africa, 2004.

Visiting Fellowship: Pediatric Hand and Brachial Plexus Surgery, l'Institut de la Main, Paris, France, 2004.

Certification: American Board of Orthopaedic Surgery, 2006; Certificate of Added Qualifications in Surgery of the Hand, The American Board of Surgery, 2009.

Cornwall R, Waters PM. Pediatric Brachial Plexus Palsy. In Wolfe SW, et al (eds): Green's Operative Hand Surgery. 7th ed. Elsevier. 2017;1391-1424.

Dua K, Abzug JM, Bauer AS, Cornwall R, Wyrick TO. Pediatric distal radius fractures. Instr Course Lect. 2017;66:447-460.

Godfrey J, Cornwall R. Pediatric metacarpal fractures. Instr Course Lect. 2017;66:437-445.

Ting B, Bauer AS, Abzug JM, Cornwall R, Wyrick TO, Bae DS. Pediatric scaphoid fractures. Instr Course Lect. 2017;66:429-436.

Abzug JM, Dua K, Bauer AS, Cornwall R, Wyrick TO. Pediatric Phalanx Fractures. J Am Acad Orthop Surgeons. 2016;24(11):e174-e183.

Little K, Cornwall R. Congenital Anomalies of the Hand-Principles of Management. Ortho Clin NA. 2016 Jan;47(1):153-68.

Eismann E, Laor T, Cornwall R. Three dimensional magnetic resonance imaging of glenohumeral dysplasia in neonatal brachial plexus palsy. J Bone Joint Surg Am. 2016;98(2):142-51.

Nikolaou S, Hu L, Cornwall R. Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model. J Hand Surg Am. 2015;40(10):2007-16.

Cheng W, Cornwall R, Crouch DL, Li Z, Saul KR. Contributions of Muscle Imbalance and Impaired Growth to Postural and Osseous Shoulder Deformity Following Brachial Plexus Birth Palsy: A Computational Simulation Analysis. J Hand Surg Am. 2015;40(6):1170-6.

Eismann EA, Little KJ, Laor T, Cornwall R. Glenohumeral abduction contracture in children with unresolved neonatal brachial plexus palsy. J Bone Joint Surg Am. 2015 Jan 21;97(2):112-8.

Grants

The Role of Satellite Cells in Contracture Formation Following Neonatal Brachial Plexus Injury. Principal Investigator. Career Development Award, Orthopaedic Research and Education Foundation. Jul 2013-Jun 2016.

Steven A. Crone, PhD

Steven A. Crone, PhD, focuses his research around understanding how neurons form functioning motor circuits during development and how the function (or dysfunction) of motor circuits impacts neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy.
Visit the Crone Lab.

513-803-9275 steven.crone@cchmc.org

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Steven A. Crone, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-9275

Email steven.crone@cchmc.org

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Developmental biology; neurodegenerative disease; neural control of behavior; locomotion; respiration; motor circuits; amyotrophic lateral sclerosis (ALS); spinal muscular atrophy (SMA)

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Biography

Steven Crone, PhD, is an assistant professor in the Division of Pediatric Neurosurgery within the UC Department of Surgery. He received his BS with honors from The Pennsylvania State University in 1995. He received his PhD from the University of California, San Diego while performing his thesis research at The Salk Institute for Biological Studies.

His thesis research demonstrated that the ErbB2 receptor tyrosine kinase is essential for maintenance of the enteric nervous system and prevention of dilated cardiomyopathy. His research has important implications for the treatment of Hirschsprung’s disease, heart disease and ErbB2/Her2 dependent breast cancer.

Dr. Crone performed his postdoctoral work at the University of Chicago where he used transgenic mouse models to label, ablate or alter gene expression in specific interneurons to establish that V2a neurons coordinate limb movement during locomotion and promote a normal breathing rhythm.

He joined Cincinnati Children’s Hospital Medical Center in September of 2012 where his laboratory will investigate how motor circuits are altered by injury or disease.

BS: The Pennsylvania State University, University Park, PA, 1995.

PhD: University of California, San Diego and The Salk Institute for Biological Studies, San Diego, CA, 2003.

Postdoctoral: University of Chicago, Chicago, IL, 2012.

Crone SA, Viemari J-C, Droho S, Ramirez J, Mrejeru A, Sharma K. Irregular breathing in mice following genetic ablation of V2a neurons. J Neuroscience. 2012;32(23):7895–7906.

Zhong G, Droho S, Crone SA, Dietz S, Kwan AC, Webb WW, Sharma K, Harris-Warrick R. Electrophysiological characterization of the V2a interneurons and their locomotor-related activity in the neonatal mouse spinal cord. J Neuroscience. 2010;30(1):170-182.

Crone SA, Zhong G, Harris-Warrick R, Sharma K. In mice lacking V2a interneurons, gait depends on speed of locomotion. J Neuroscience. 2009;29(21):7098-7109.

Crone SA, Quinlan KA, Zagoraiou L, Droho S, Restrepo CE, Lundfald L, Endo T, Setlak J, Jessell TM, Kiehn O, Sharma K. Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron. 2008;60:70-83.

Joseph NM, Mukouyama Y, Mosher JT, Jaegle M, Crone SA, Dormand E, Lee K-F, Meijer D, Anderson DJ, Morrison SJ. Neural crest stem cells undergo multi-lineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development. 2004;131:5599-5612.

Crone SA, Negro A, Trumpp A, Giovannini M, Lee K-F. Colonic epithelial expression of ErbB2 is required for postnatal maintenance of the enteric nervous system. Neuron. 2003;37:29-40.

Crone SA, Zhao Y-Y, Fan L, Gu Y, Minamisawa S, Liu Y, Peterson KL, Chen J, Kahn R, Condorelli G, Ross J Jr, Chien KR, Lee K-F. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nature Medicine. 2002;8:459-465.

Crone SA, Lee K-F. Gene targeting reveals multiple essential functions of the neuregulin signaling system during development of the neuroendocrine and nervous systems. Annals of the New York Academy of Sciences. 2002;971:547-553.

Kaspar BK, Vissel B, Bengoechea T, Crone S, Randolph-Moore L, Muller R, Brandon EP, Schaffer D, Verma IM, Lee K-F, Heinemann SF, Gage FH. Adeno-associated virus effectively mediates conditional gene modification in the brain. Proceedings of the National Academy of Sciences USA. 2002;99:2320-5.

Tony J. De Falco, PhD

Tony J. De Falco, PhD, has basic research programs in gonad differentiation and homeostasis. His lab investigates how the initially undifferentiated gonad primordium transforms into a testis or ovary, as well as how the adult testis maintains sperm production over a long reproductive lifespan. His specific interests are in the novel and diverse roles of myeloid immune cells in reproductive biology.

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513-803-3988 tony.defalco@cchmc.org

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Tony J. De Falco, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-3988

Email tony.defalco@cchmc.org

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Differentiation of the fetal gonad into a sexually dimorphic and structurally specialized organ; spermatogonial differentiation; roles of myeloid cells in tissue remodeling, organ vascularization and spermatogonial development.

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BA: University of Virginia, Charlottesville, VA.

PhD: Johns Hopkins University, Baltimore, MD.

Postdoc: Duke University Medical Center, Durham, NC.

Postdoc: National Institute of Genetics, Mishima, Japan.

Sun X, Ito J, Potter SJ, Dey SK, DeFalco T. Extra-gonadal oocytes residing in the mouse ovarian hilum contribute to fertility. Biol Reprod. 2017;96(5):1060-1070.

Lin YT, Barske L, DeFalco T, Capel B. Numb regulates somatic cell lineage commitment during early gonadogenesis in mice. Development. 2017;144(9):1607-1618. (This article was featured in an “In This Issue” preview article in the May 1, 2017 issue of Development.)

Potter SJ, DeFalco T. Role of the testis interstitial compartment in spermatogonial stem cell function. Reproduction. 2017;153(4):R151-R162.

DeFalco T*, Potter SJ, Williams AV, Waller B, Kan MJ, Capel B. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis**. Cell Rep. 2015;12(7):1107-19. (*corresponding author) (**Featured Article on the cover of the August 18th issue of Cell Reports, and also highlighted as a Preview in Cell Reports and as a featured article in the “World of Reproductive Biology” in Biology of Reproduction)

Potter SJ, DeFalco T. Using ex vivo upright droplet cultures of whole fetal organs to study developmental processes during mouse organogenesis. J Vis Exp. 2015;104:e53262.

DeFalco T*, Bhattacharya I, Williams AV, Sams, DM, Capel, B.* Yolk-sac-derived macrophages regulate fetal testis vascularization and morphogenesis. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):E2384-2393. (*co-corresponding authors)

DeFalco T, Saraswathula A, Briot A, Iruela-Arispe ML, Capel B. Testosterone levels influence mouse fetal Leydig cell progenitors through Notch signaling. Biol Reprod. 2013 Apr 11;884:91.

Jameson S, Natarajan A, Cool J, DeFalco T, Maatouk D, Mork L, Munger SC, Capel B. Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad. PLoS Genet. 2012;8(3):e1002575.

DeFalco T, Takahashi S, Capel B. Two distinct origins for Leydig cell progenitors in the fetal testis. Dev Biol. 2011 Apr 1;352(1):14-26.

Cool J, DeFalco TJ, Capel B. Vascular-mesenchymal cross-talk through Vegf and Pdgf drives organ patterning. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):167-172.

Grants

Macrophage regulation of the spermatogonial stem cell niche. Principal Investigator. National Institutes of Health Maximizing Investigators’ Research Award (MIRA/R35)/National Institute of General Medical Sciences. Sep 2016 - May 2021.

Prasad Devarajan, MD Director, Division of Nephrology and Hypertension

Prasad Devarajan, MD, researches acute kidney injury mechanisms, biomarkers and novel therapies. He also studies focal segmental glomerulosclerosis pathogenesis and biomarkers; and lupus nephritis molecular pathways and biomarkers. For each condition, his team employs an integrated approach of genomic and proteomic discovery in animal and human models, followed by translation, and validation in the human disease states.
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513-636-4531 prasad.devarajan@cchmc.org

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Prasad Devarajan, MD

Director, Division of Nephrology and Hypertension

Medical Director, Stone Center

Director, Nephrology and Hypertension Clinical Laboratory

Louise M. Williams Endowed Chair

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4531

Fax 513-636-7407

Email prasad.devarajan@cchmc.org

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Clinical specialties: acute kidney injury, nephrotic syndrome, kidney stones

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Premedical Studies: Bombay University, India, 1979.

MD: Bombay University, India, 1985.

Brunner HI, Gulati G, Klein-Gitelman MS, Rouster-Stevens KA, Tucker L, Ardoin SP, Onel KB, Mainville R, Turnier J, Aydin POA, Witte D, Huang B, Bennett MR, Devarajan P. Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus. Pediatr Nephrol. 2018 Aug 29.

Chihanga T, Ma Q, Nicholson JD, Ruby HN, Edelmann RE, Devarajan P, Kennedy MA. NMR Spectroscopy and Electron Microscopy Identification of Metabolic and Ultrastructural Changes to the Kidney Following Ischemia Reperfusion Injury. Am J Physiol Renal Physiol. 2018 Feb 1;314(2):F154-F166.

Bennett MR, Pyles O, Ma Q, Devarajan P. Preoperative levels of urinary uromodulin predict acute kidney injury after pediatric cardiopulmonary bypass surgery. Pediatr Nephrol. 2018 Mar;33(3):521-526.

Varnell CD Jr, Goldstein SL, Devarajan P, Basu RK. Impact of Near Real-Time Urine Neutrophil Gelatinase-Associated Lipocalin Assessment on Clinical Practice. Kidney Int Rep. 2017 Jun 3;2(6):1243-1249.

Bennett MR, Ma Q, Ying J, Devarajan P, Brunner H. Effects of age and gender on reference levels of biomarkers comprising the pediatric Renal Activity Index for Lupus Nephritis (p-RAIL). Pediatr Rheumatol Online J. 2017 Oct 13;15(1):74.

Pleasant L, Ma Q, Devarajan M, Parameswaran P, Drake K, Siroky B, Shay-Winkler K, Robbins J, Devarajan P. Increased Susceptibility to Structural Acute Kidney Injury in a Mouse Model of Presymptomatic Cardiomyopathy. Am J Physiol Renal Physiol. 2017 Sep 1;313(3):F699-F705.

Nehus E, Kaddourah A, Pyles O, Bennett M, Devarajan P. Subclinical Kidney Injury in Children Receiving Nonsteroidal Anti-Inflammatory Drugs after Cardiac Surgery. J Pediatr. 2017 Oct;189:175-180.

Dong L, Ma Q, Bennett M, Devarajan P. Urinary Biomarkers of Cell Cycle Arrest are Delayed Predictors of Acute Kidney Injury After Pediatric Cardiopulmonary Bypass. Pediatr Nephrol. 2017 Dec;32(12):2351-2360.

Bennett MR, Pleasant L, Haffner C, Ma Q, Haffey WD, Ying J, Wagner M, Greis KD, Devarajan P. A Novel Biomarker Panel to Identify Steroid Resistance in Childhood Idiopathic Nephrotic Syndrome. Biomarker Insights. 2017;12:1177271917695832.

Brunner HI, Bennett MR, Gulati G, Abulaban K, Klein-Gitelman MS, Ardoin SP, Tucker LB, Rouster-Stevens KA, Witte D, Ying J, Devarajan P. Urine Biomarkers to Predict Response to Lupus Nephritis Therapy in Children and Young Adults. J Rheumatol. 2017 Aug;44(8):1239-1248.

Sudhansu K. Dey, PhD Lova Riekert Chair, Cancer and Cell Biology

SK Dey, PhD, investigates the paracrine, autocrine and juxtacrine signaling networks that influence uterine biology in the context of embryo-uterine interactions during pregnancy. He also works on the effects of endocannabinoids on periimplantation events. Studies involving the molecular and genetic regulation of epithelial ovarian cancer and uterine carcinoma are also of interest.
Visit the Dey Lab.

513-803-1158 sk.dey@cchmc.org

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Sudhansu K. Dey, PhD

Lova Riekert Chair, Cancer and Cell Biology

Director, Division of Reproductive Sciences

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-1158

Fax 513-803-1160

Email sk.dey@cchmc.org

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Prostaglandin-nuclear receptor-angiogenic signaling axis during embryo implantation with special emphasis to cPLA2α-Cox2-PPARδ-Vegf network in the uterus; cytokine-growth factor-homeobox-morphogen signaling axis in implantation involving Lif-Hb-Egf-Hoxa10/Msx1-Ihh/Bmp/Wnt network in the uterus; immunophilin/cochaperone-nuclear signaling in the mouse uterus during implantation involving Fkbp52-PR; ligand-receptor signaling with endocannabinoids during the periimplantation events in mice in the context of anandamide interacting with G-protein coupled receptors, CB1 and CB2; molecular and genetic basis of epithelial ovarian cancer with special reference to prostaglandin-PPAR signaling; miRNA and Cox-2 regulation in uterine biology and cancer; Pten and uterine carcinoma: conditionally gene deleted mouse models

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Biography

Dr. Dey received his PhD from The University of Calcutta College of Sciences in 1972, after which he received postdoctoral training at the University of Kansas Medical Center from 1973-1977, followed by his faculty appointment in 1977 where he rose to the rank of University Distinguished Professor. He moved to Vanderbilt University as Dorothy Overall Wells professor of pediatrics, cell and developmental biology and pharmacology in 2002. In both places he directed NIH-funded reproductive biology training grants. In 2008, Dr. Dey moved to Cincinnati Children’s Hospital Medical Center as Lova Riekert Chair and professor of pediatrics within the University of Cincinnati College of Medicine to start a new Division of Reproductive Sciences. He has published over 300 original articles and has been funded by two MERIT Awards, RO1 grants and a Program Project Grants from NIH, and grants from the Bill and Melinda Gates Foundation and March of Dimes Foundation. His research mission has been to define the molecular road map to embryo-uterine interactions during pregnancy. His recent work published in Developmental Cell, Nat Med, PNAS and JCI provides novel information in the context of cell polarity in implantation, ectopic pregnancy, progesterone resistance to pregnancy failure and premature decidual senescence in preterm delivery. In 2008, Dr. Dey received Carl G. Hartman Award, the highest honor of the Society for the Study of Reproduction. In 2009, he received IVI Award sponsored by Schering-Plough for best contribution in reproductive medicine.

He has graduated seven PhD students and mentored over 40 postdoctoral fellows, 20 of whom are currently independent faculty members, and most others are investigators in major research institutions. His laboratory currently consists of one junior faculty, four postdoctoral fellows, one MD/PhD student, and two research assistants.

BSc: Presidency College, Calcutta, India, 1965.

MSc: University of Calcutta, India, 1967.

PhD: University of Calcutta, India, 1972.

Cha J, Bartos A, Egashira M, Haraguchi H, Saito-Fujita T, Leishman E, Bradshaw H, Dey SK, and Hirota Y. Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions. J Clin Invest. 2013 Sep 3;123(9):4063-75.

Raines AM, Adam M, Magella B, Meyer SE, Grimes HL, Dey SK, Potter SS. Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts. Development. 2013 Jul;140(14):2942-52.

Cha J, Sun X, Bartos A, Fenelon J, Lefevre P, Daikoku T, Shaw G, Maxson R, Murphy BD, Renfree MB, Dey SK. A new role for muscle segment homeobox genes in mammalian embryonic diapause. Open Biol. 2013 Apr 24;3(4):130035.

Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012 Dec:18(12):1754-67.

Xie H, Sun X, Piao Y, Jegga AG, Handwerger S, Ko MS, Dey SK. Silencing or amplification of endocannabinoid signaling in blastocysts via CB1 compromises trophoblast cell migration. J Biol Chem. 2012 Sep 14;287(38):32288-97.

Daikoku T, Cha J, Sun X, Tranguch S, Xie H, Fujita T, Hirota Y, Lydon J, DeMayo F, Maxson R, Dey SK. Conditional Deletion of MSX Homeobox Genes in the Uterus Inhibits Blastocyst Implantation by Altering Uterine Receptivity. Dev Cell. 2011 Dec 13;21(6):1014-25.

Sun X, Xie H, Yang J, Wang H, Bradshaw HB, Dey SK. Endocannabinoid signaling directs differentiation of trophoblast cell lineages and placentation. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16887-92.

Hirota Y, Acar N, Tranguch S, Burnum KE, Xie H, Kodama A, Osuga Y, Ustunel I, Friedman DB, Caprioli RM, Daikoku T, Dey SK. Uterine FK506-binding protein 52 (FKBP52)-peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15577-82.

Hirota Y, Daikoku T, Tranguch S, Xie H, Bradshaw HB, Dey SK. Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice. J Clin Invest. 2010 Mar;120(3):803-15.

Burnum KE, Cornett DS, Puolitaival SM, Milne SB, Myers DS, Tranguch S, Brown HA, Dey SK, RM Caprioli. Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation. J Lipid Res. 2009 Nov;50(11);2290-8.

Brian Gebelein, PhD

Brian Gebelein, PhD, studies how the Hox genes specify distinct cell fates within the nervous system using the fruit fly as a model organism. His long-term goal is to use a combination of genetic and biochemical approaches to understand how Hox factors interact with neuronal transcription factors to regulate downstream target genes that pattern the nervous system and ultimately control cellular function and behavior.
Visit the Gebelein Lab.

513-636-3366 brian.gebelein@cchmc.org

Brian Gebelein, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-3366

Email brian.gebelein@cchmc.org

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Visit the Gebelein Lab.

BS: University of Wisconsin, Milwaukee, WI, 1994.

PhD: Mayo Graduate School, Rochester, MN, 2000.

Postdoctoral Fellow: Molecular mechanisms of Hox specificity in Drosophila melanogaster, Columbia University.

Charlton-Perkins M, Whitaker SL, Fei Y, Xie B, Li-Kroeger D, Gebelein B, Cook T. Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling. Neural Dev. 2011 May 3;6:20.

Gutzwiller LM, Witt LM, Gresser AL, Burns KA, Cook TA, Gebelein B. Proneural and abdominal Hox inputs synergize to promote sensory organ formation in the Drosophila abdomen. Dev Biol. 2010 Dec 15;348(2):231-43.

McDonald EC, Xie B, Workman M, Charlton-Perkins M, Terrell DA, Reischl J, Wimmer EA, Gebelein BA, Cook TA. Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events. Dev Biol. 2010 Nov 1;347(1):122-32.

Phelan JD, Shroyer NF, Cook T, Gebelein B, Grimes HL. Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. Curr Opin Hematol. 2010 Jul;17(4):300-7.

Witt LM, Gutzwiller LM, Gresser AL, Li-Kroeger D, Cook TA, Gebelein B. Atonal, Senseless, and Abdominal-A regulate rhomboid enhancer activity in abdominal sensory organ precursors. Dev Biol. 2010 Aug 15;344(2):1060-70.

Uhl JD, Cook TA, Gebelein B. Comparing anterior and posterior Hox complex formation reveals guidelines for predicting cis-regulatory elements. Dev Biol. 2010 Jul 1;343(1-2):154-66.

Horman SR, Velu CS, Chaubey A, Bourdeau T, Zhu J, Paul WE, Gebelein B, Grimes HL. Gfi1 integrates progenitor versus granulocytic transcriptional programming. Blood. 2009 May 28;113(22):5466-75.

Gebelein B. The control of EGF signaling and cell fate in the Drosophila abdomen. Fly (Austin). 2008 Sep-Oct;2(5):257-8.

Li-Kroeger D, Witt LM, Grimes HL, Cook TA, Gebelein B. Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS. Dev Cell. 2008 Aug;15(2):298-308.

Xie B, Charlton-Perkins M, McDonald E, Gebelein B, Cook T. Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development. 2007 Dec;134(23):4243-53.

Rashmi S. Hegde, PhD

Rashmi S. Hegde, PhD, studies molecular mechanisms involved in embryonic organ development and how the aberrant functioning of these processes can lead to developmental disorders as well as adult disease states such as cancer. This knowledge is then utilized in the rational design of therapeutic strategies. We use a variety of experimental techniques including biochemistry, cell biology and structural biology.
Visit the Hedge Lab.

513-636-5947 rashmi.hegde@cchmc.org

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Rashmi S. Hegde, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-5947

Fax 513-636-6772

Email rashmi.hegde@cchmc.org

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Clinical

Pre-clinical validation of anti-angiogenic agents for use in the treatment of retinopathies, cancer and pulmonary disease.

Research

Molecular mechanisms involved in normal development and in disease states using in vitro (cellular and solution biochemistry and structural biology) and in vivo (mouse models) strategies; developing novel therapeutic strategies via structure-aided drug design coupled with in vitro validation and in vivo pre-clinical studies.

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Biography

Rashmi Hegde received her PhD in medicinal chemistry from the University of Pittsburgh in 1989. She received post-doctoral training in the Department of Molecular Biophysics and Biochemistry at Yale University, where she was a fellow of the National Cancer Center. She was appointed assistant professor of biochemistry at New York University School of Medicine and the Skirball Institute of Biomolecular Medicine in 1994. She is presently a full professor in the Division of Developmental Biology at Children's Hospital Research Foundation within the Department of Pediatrics at the University of Cincinnati College of Medicine.

PhD: University of Pittsburgh, Pittsburgh, PA, 1989.

Post-doctoral Fellowship: Yale University, 1989-1994.

Assistant Professor: New York University School of Medicine, Skirball Institute, 1994-2000.

Associate Professor: Cincinnati Children's Hospital Medical Center, 2001-2007.

Professor: Cincinnati Children's Hospital Medical Center, 2008-present.

Hufnagel RB, Arno G, Hein ND, Hersheson J, Prasad M, Anderson Y, Laura A, Krueger LA, Gregory LC, Stoetzel C, Jaworek TJ, Hull S, Li A, Plagnol V, Willen CM, Morgan TM, Prows CA, Hegde RS, Riazuddin S, Grabowski GA, Richardson RJ, Dieterich K, Huang T, Revesv T, Martinez-Barbera JP, Sisk RA, Jefferies C, Houlden H, Dattani MT, Fink JK, Dollfus H, Moore AT, Ahmed ZM. Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes. J Med Genet. 2015 Feb;52(2):85-94.

Simon EM,Richard EM, Wang X, Shahzad M, Huang VH, Qaiser TA, Potluri P, Mahl SE, Davila A, Nazli S, Hancock S, Yu M, Gargus J, Chang R, Al-Sheqaih N, Newman WG, Abdenur J, Starr A, Hegde RS, Dorn T, Busch A, Park E, Wu J, Schwenzer H, Flieri A, Florentz C, Sissler M, Khan SN, Guan MX, Friedman TB, Wu DK, Procaccio V, Riazuddin S, Wallace DC, Ahmed ZM, Huang T, Riazuddin S. Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome. PLoS Genetics. 2015 Mar 25;11(3):e1005097.

Seco CZ, Giese AP, Shafique S, Schraders M, Oonk AM, Grossheim M, Oostrik J, Strom T, Hegde R, van Wijk E, Frolenkov GI, Azam M, Yntema HG, Free RH, Riazuddin S, Verheij JB, Admiraal RJ, Qamar R, Ahmed ZM, Kremer H. Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells. Eur J Hum Genet. 2015 Jul 15. (Epub ahead of print).

Broering TJ, Wang YL, Pandey RN, Hegde RS, Wang SC, Namekawa SH. BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during spermatogenesis. Biol Open. 2015 May 15;4(7):873-84.

Pandey RN, Wang TS, Tadjuidje E, McDonald MG, Rettie AE, Hegde RS. Structure-activity relationships of benzbromarone metabolites and derivatives as EYA inhibitory anti-angiogenic agents. PLoS One. 2013 Dec 18;8(12):e84582.

Rao S, Chun C, Fan J, Kofron M, Hegde RS, Ferrara N, Yang MB, Copenhagen D, Lang RA. A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature. 2013 Feb 14;494(7436):243-6.

Tadjuidje E, Hegde RS. The Eyes Absent proteins in development and disease. Cell Mol Life Sci. 2013 Jun;70(11):1897-913.

Korfhagen TR, Kitzmiller J, Chen G, Hegde RS, Divanovic S, Karp CL, Whitsett JA. SAM-pointed domain ETS factor mediates epithelial cell-intrinsic innate immune signaling during airway mucous metaplasia. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16630-5.

Riazuddin S, Belyantseva IA, Giese A, Kwanghyuk L, Indzhykulian A, Nandamuri SP, Yousaf R, Sue Lee, Terrell D, Hegde RS, Morell RJ, Ali RA, Anwar S, Rachel RA, Andrade-Elizondo PB, Sirmaci A, Husnain T, Khan SN, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Swaroop A, Ahmad W, Tekin M, Riazuddin S, Cook T, Buschbeck EK, Frolenkov GI, Leal S, Friedman TB, Ahmed Z. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet. 2012 Nov;44(11):1265-71.

Tadjuidje E, Wang TS, Pandey RN, Sumanas S, Lang RA, Hegde RS. The EYA tyrosine phosphatase activity is pro-angiogenic and is inhibited by benzbromarone. PLoS One. 2012;7(4):e34806.

Stacey S. Huppert, PhD

Stacey S. Huppert, PhD, investigates the cellular contribution and molecular factors required for assembly of the three-dimensional hepatic architecture, during liver development, homeostasis and regeneration. Defining the critical elements involved in formation and repair processes of the liver are necessary not only to understand biology, but also to identify the cellular and molecular targets involved in congenital and chronic liver diseases.

Visit the Huppert Lab.

513-803-3871 stacey.huppert@cchmc.org

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Stacey S. Huppert, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-3871

Email stacey.huppert@cchmc.org

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Hepatic cell plasticity, development and regeneration; reprogramming; three-dimensional hepatic architecture; Notch signaling; hepatobiliary disease

Visit the Huppert Lab.

BS: Genetic Biology,Purdue University, West Lafayette, IN, 1992.

PhD: Genetics, Indiana University, Bloomington, IN, 1998.

Postdoctoral Fellow: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2003.

Instructor: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2005.

Assistant Professor: Cell and Developmental Biology, Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 2012.

Schaub JR, Huppert KA, Kurial SNT, Hsu BY, Cast AE, Donnelly B, Karns RA, Chen F, Rezvani M, Luu HY, Mattis AN, Rougemont AL, Rosenthal P, Huppert SS, Willenbring H. De novo formation of the biliary system by TGFbeta-mediated hepatocyte transdifferentiation. Nature. 2018 May;557(7704):247-251.

Broadus MR, Chen TW, Neitzel LR, Ng VH, Jodoin JN, Lee LA, Salic A, Robbins DJ, Capobianco AJ, Patton JG, Huppert SS, Lee E. Identification of a Paralog-Specific Notch1 Intracellular Domain Degron. Cell Rep. 2016 May 31;15(9):1920-9.

Poling HM, Mohanty SK, Tiao GM, Huppert SS. A comprehensive analysis of aquaporin and secretory related gene expression in neonate and adult cholangiocytes. Gene Expr Patterns. 2014 Jun 12;15(2):96-103.

Walter TJ, Cast AE, Huppert KA, Huppert SS. Epithelial VEGF signaling is required in the mouse liver for proper sinusoid endothelial cell identity and hepatocyte zonation in vivo. Am J Physiol Gastrointest Liver Physiol. 2014 May 15;306(10):G849-62.

Walter TJ, Vanderpool C, Cast AE, Huppert SS. Intrahepatic bile duct regeneration in mice does not require Hnf6 or Notch signaling through Rbpj. Am J Pathol. 2014 May;184(5):1479-88.

Walter TJ, Sparks EE, Huppert SS. 3-dimensional resin casting and imaging of mouse portal vein or intrahepatic bile duct system. J Vis Exp. 2012 Oct 25;(68):e4272.

Humphreys R, Zheng W, Prince LS, Qu X, Brown C, Loomes K, Huppert SS, Baldwin S, Goudy S. Cranial neural crest ablation of Jagged1 recapitulates the craniofacial phenotype of Alagille syndrome patients. Hum Mol Genet. 2012 Mar 15;21(6):1374-83.

Vanderpool C, Sparks EE, Huppert KA, Gannon M, Means AL, Huppert SS. Genetic interactions between hepatocyte nuclear factor-6 and Notch signaling regulate mouse intrahepatic bile duct development in vivo. Hepatology. 2012 Jan;55(1):233-43.

Sparks EE, Perrien DS, Huppert KA, Peterson TE, Huppert SS. Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice. Dis Model Mech. 2011 May;4(3):359-67.

Sparks EE, Huppert KA, Brown MA, Washington MK, Huppert SS. Notch signaling regulates formation of the three-dimensional architecture of intrahepatic bile ducts in mice. Hepatology. 2010 Apr;51(4):1391-400.

Makiko Iwafuchi-Doi, PhD

Makiko Iwafuchi-Doi, PhD, is keen to reveal chromatin regulatory principles underlying dramatic cell fate changing events that occur in embryonic development, tissue repair (physiological reprogramming), and diseases, and ultimately to utilize this knowledge to precisely engineer cell fates.

513-636-0882 makiko.doi@cchmc.org

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Makiko Iwafuchi-Doi, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-0882

Email makiko.doi@cchmc.org

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Chromatin regulation; pioneer transcription factors; cell programming and reprogramming

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Biography

Makiko Iwafuchi-Doi, PhD, is an assistant professor of pediatrics in the Division of Developmental Biology at Cincinnati Children’s Hospital Medical Center within the University of Cincinnati College of Medicine. She received her PhD from Osaka University in Japan where she studied gene regulatory networks underlying neural plate development in vertebrates. She performed her postdoctoral training at the University of Pennsylvania where her research focused on basic mechanisms by which pioneer transcription factor FoxA regulates the configuration of chromatin. While at Penn she received postdoctoral fellowships from JSPS, Naito, Astellas, and Uehara foundations. She joined Cincinnati Children’s Hospital Medical Center in November 2017.

BSc: Kitasato University, Japan.

PhD: Osaka University, Japan.

Postdoctoral Fellow: University of Pennsylvania, Philadelphia, PA.

Zaret KS, Lerner J, Iwafuchi-Doi M. Chromatin Scanning by Dynamic Binding of Pioneer Factors. Mol Cell. 2016 Jun 2;62(5):665-7.

Iwafuchi-Doi M, Zaret KS. Cell Fate Control by Pioneer Transcription Factors. Development. 2016 Jun 1;143(11):1833-7.

Iwafuchi-Doi M, Donahue G, Kakumanu A, Watts JA, Mahony S, Pugh BF, Lee D, Kaestner KH, Zaret KS. The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation. Mol Cell. 2016 Apr 7;62(1):79-91.

Iwafuchi-Doi M, Zaret KS. Pioneer Transcription Factors in Cell Reprogramming. Genes & Development. 2014;28:2679-92.

Iwafuchi-Doi M, Matsuda K, Murakami K, Niwa H, Tesar PJ, Aruga J, Matsuo I, Kondoh H. Transcriptional Regulatory Networks in Epiblast Cells and During Anterior Neural Plate Development as Modeled in Epiblast Stem Cells. Development. 2012 Nov;139(21):3926-37.

Iwafuchi-Doi M, Yoshida Y, Onichtchouk D, Leichsenring M, Driever W, Takemoto T, Uchikawa M, Kamachi Y, Kondoh H. The Pou5f1/Pou3f-Dependent but SoxB-Independent Regulation of Conserved Enhancer N2 Initiates Sox2 Expression During Epiblast to Neural Plate Stages in Vertebrates. Dev Biol. 2011 Apr 15;352(2):354-66.

Rulang Jiang, PhD Member, Division of Developmental Biology

Rulang Jiang, PhD, is a mouse geneticist directing programs in craniofacial development and musculoskeletal disease research. His lab generates and uses mutant mouse models to investigate the genetic and developmental mechanisms of craniofacial birth defects, including cleft lip, cleft palate, frontonasal malformation, micrognathia, and dental anomalies. Other ongoing projects investigate the genetic control of tendon development and homeostasis, and mechanisms of heterotopic ossification.

Visit the Jiang Lab.

513-636-3212 rulang.jiang@cchmc.org

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Rulang Jiang, PhD

Member, Division of Developmental Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3212

Email rulang.jiang@cchmc.org

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Genetic basis and developmental mechanisms of congenital craniofacial malformations; tendon development, homeostasis, and heterotopic ossification

Biography

Rulang Jiang, PhD, is professor of Pediatrics at Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine. Prior to joining Cincinnati Children's in 2011, he was a tenured professor of Biomedical Genetics at University of Rochester School of Medicine and Dentistry where he established and led a continuously NIH-funded program in the areas of craniofacial development and birth defect research from 1999 to 2011. At Cincinnati Children's, he has expanded research program into understanding of musculoskeletal diseases and tissue repair/regeneration. In addition to NIH grant support, his research is supported by the Shriners Hospital for Children.

BS: Nanjing Normal University, Nanjing, China, 1984.

MS: Genetics, Chinese Academy of Sciences, Beijing, China, 1987.

PhD: Wesleyan University, Middletown, CT, 1995.

Li C, Lan Y, Krumlauf R, Jiang R. Modulating Wnt signaling rescues palate morphogenesis in Pax9 mutant mice. Journal of Dental Research. 2017;96(11):1273-1281.

Li C, Lan Y, Jiang R. Molecular and Cellular Mechanisms of Palate Development. Journal of Dental Research. 2017;96(11):1184-1191.

Kwon H-JE, Jia S, Lan Y, Liu H, Jiang R. Activin and BMP4 signaling converge on Wnt activation during odontogenesis. Journal of Dental Research. 2017;96(10):1145-1152.

Han L, Xu J, Grigg E, Slack M, Chaturvedi P, Jiang R, Zorn AM. Osr1 functions downstream of Hedgehog pathway to regulate foregut development. Developmental Biology. 2017;427(1):72-83.

Fu X, Xu J, Chaturvedi P, Liu H, Jiang R, Lan Y. Identification of Osr2 Transcriptional target genes in palate development. Journal of Dental Research. 2017;96(12):1451-1458.

Xu J, Liu H, Lan Y, Aronow BJ, Kalinichenko VV, Jiang R. A Shh-Foxf-Fgf18-Shh molecular circuit regulating palate development. PLOS Genetics. 2016;12(1):e1005769.

Lan Y, Zhang N, Liu H, Xu J, Jiang R. Golgb1 regulates protein glycosylation and is crucial for mammalian palate development. Development. 2016;143:2344-2355.

Xu J, Liu H, Chai OH, Lan Y, Jiang R. Osr1 interacts synergistically with Wt1 to regulate kidney organogenesis. PLOS One. 2016;11(7):e0159597.

Jia S, Kwon H-JE, Lan Y, Zhou J, Liu H, Jiang R. Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through antagonistic regulation of secreted Wnt antagonists. Developmental Biology. 2016;420(1):110-119.

Liu H, Xu J, Liu C-F, Lan Y, Wylie C, Jiang R. Whole transcriptome expression profiling of mouse limb tendon development by using RNA-seq. Journal of Orthopaedic Research. 2015;33:840-848.

Grants

Visit the Kalinichenko Lab.

Mandible Development. Principal Investigator. National Institutes of Health. Jul 2017-Jun 2022.

Molecular Patterning of Mammalian Dentition. Principal Investigator. National Institutes of Health. Jul 2009-Jun 2018.

Molecular Regulation of Palate Development. Principal Investigator. Shriners Hospital for Children Research Grant. Jan 2017-Dec 2021.

Vladimir V. Kalinichenko, MD, PhD

Vladimir V. Kalinichenko, MD, PhD, is investigating the transcriptional regulation of epithelial and endothelial cell functions during lung embryonic development and lung carcinogenesis. He studies the winged helix/forkhead box (Fox) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival, ultimately identifying novel mechanisms that cause human lung malformations and promote lung cancer formation.

513-636-4822 vladimir.kalinichenko@cchmc.org

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Vladimir V. Kalinichenko, MD, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4822

Fax 513-636-2423

Email vladimir.kalinichenko@cchmc.org

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Visit the Kalinichenko Lab.

Clinical

Lung development; cell proliferation; carcinogenesis; transcriptional regulation of gene expression.

Research

Transcriptional regulation of epithelial and endothelial cell functions during lung embryonic development and lung carcinogenesis; winged helix/forkhead box (Fox) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival; identify and increase understanding of currently unknown mechanisms that cause human lung malformations and promote lung cancer formation.

MD: Russian State Medical University, Moscow, Russia, 1993.

PhD: Russian State Medical University, Moscow, Russia, 1995.

Fellowship: From the European Soros Foundation, 1995.

Postdoctoral: University of Illinois at Chicago, Center for Molecular Biology, IL, 2000.

Postdoctoral: University of Illinois at Chicago, Department of Molecular Genetics, IL, 2002.

Wang IC, Ustiyan V, Zhang Y, Cai Y, Kalin TV, Kalinichenko VV. Foxm1 transcription factor is required for the initiation of lung tumorigenesis by oncogenic KrasG12D. Oncogene. 2014 Nov13;33(46):5391-6.

Ren X, Shah T, Ustiyan V, Zhang Y, Shinn J, Chen G, Whitsett JA, Kalin TV, Kalinichenko VV. FOXM1 Promotes Allergen-Induced Goblet Cell Metaplasia and Pulmonary Inflammation. Mol Cell Biol. 2013 Jan;33(2):371-86.

Wang IC, Snyder J, Zhang Y, Lander J, Nakafuku Y, Lin J, Chen G, Kalin TV, Whitsett JA, Kalinichenko VV. Foxm1 mediates a cross-talk between Kras/MAPK and canonical Wnt signaling pathways during development of respiratory epithelium. Mol Cell Biol. 2012 Oct;32(19):3838-50.

Ustiyan V, Wert SE, Ikegami M, Wang IC, Kalin TV, Whitsett JA, Kalinichenko VV. Foxm1 Transcription Factor Is Critical for Proliferation and Differentiation of Clara Cells during Development of Conducting Airways. Dev Biol. 2012 Oct 15;370(2):198-212.

Ren X, Zhang Y, Snyder J, Cross ER, Shah TA, Kalin TV, Kalinichenko VV. Forkhead Box M1 Transcription Factor Is Required for Macrophage Recruitment during Liver Repair. Mol Cell Biol. 2010 Nov;30(22):5381-93.

Wang IC, Zhang Y, Snyder J, Sutherland MJ, Burhans MS, Shannon JM, Park HJ, Whitsett JA, . Kalinichenko VV. Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia. Dev Biol. 2010 Nov 15;347(2):301-14.

Ustiyan V, Wang IC, Ren X, Zhang Y, Snyder J, Xu Y, Wert SE, Lessard JL, Kalin TV, Kalinichenko VV. Forkhead Box M1 Transcriptional Factor is Required for Smooth Muscle Cells during Embryonic Development of Blood Vessels and Esophagus. Dev Biol. 2009 Dec 15;336(2):266-79.

Kalin TV, Wang IC, Meliton L, Zhang Y, Wert SE, Ren X, Snyder J, Graf L Jr, Whitsett JA, Kalinichenko VV. Forkhead Box M1 Transcription Factor is Required for Perinatal Lung Function. Proc Natl Acad Sci USA. 2008 Dec;9105(49):19330-5.

Malin D, Kim IM, Boetticher E, Kalin TV, Ramakrishna S, Meliton L, Ustiyan V, Zhu X, Kalinichenko VV. Forkhead Box F1 Is Essential for Migration of Mesenchymal Cells and Directly Induces Integrin-Beta3 Expression. Mol Cell Biol. 2007 Apr;27(7):2486-98.

Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH, Kalinichenko VV. The Forkhead Box m1 Transcription Factor Stimulates the Proliferation of Tumor Cells during Development of Lung Cancer. Cancer Res. 2006 Feb 15;66(4):2153-61.

J. Matthew Kofron, PhD Director, Confocal Imaging Core

513-803-9055 matthew.kofron@cchmc.org

Raphael Kopan, PhD Director, Division of Developmental Biology

Raphael Kopan, PhD, and his lab have the long-term goal of organogenesis in vitro. They focus their efforts on Notch signaling as their lead into mechanistic understanding of tissue diversity using genetic engineering, embryology and single cell profiling. They interrogate the mouse embryo to address critical questions regarding the circuit logic of Notch signaling in mammalian organogenesis and its integration in larger signaling context.

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513-636-1299

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Raphael Kopan, PhD

Director, Division of Developmental Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-1299

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Notch signaling; kidney organogenesis; skin organogenesis; TSLP signaling in cancer

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Biography

Raphael Kopan, PhD, who is a professor of developmental biology at Cincinnati Children's Hospital Medical Center within the University of Cincinnati College of Medicine, has carried out seminal work in the field of Notch biology. This work has, and continues to have, an enormous impact on our understanding of normal tissue development and renewal, Alzheimer's disease and cancer-related research. In deciphering the mode of Notch activation and demonstrating the use of inhibitors to modulate Notch activity, Dr. Kopan's work laid the groundwork for the therapeutic use of γ-secretase inhibitors in the treatment of cancers, currently in clinical trials. His current interests in organogenesis are focused on two modular organs - skin and kidney - in which his group is trying to understand how interplay among the same seven pathways results in activation of distant programs. Dr. Kopan's work has resulted in 120 scientific articles as of 2013. He is the co-inventor of one patent, and he has served on scientific advisory boards as well as being a consultant to the pharmaceutical industry.

BS, MsC: Department of Zoology, Tel-Aviv University, Israel.

PhD: Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL.

Post-doctoral training : The Fred Hutchinson Cancer Research Center, Seattle, WA.

Chen S, Brunskill EW, Potter SS, Dexheimer PJ, Salomonis N, Aronow BJ, Hong CI, Zhang T, Kopan R. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan. Developmental Cell. 2015;35:49-62.

Hass MR, Liow HH, Chen X, Sharma A, Inoue YU, Inoue T, Reeb A, Martens A, Fulbright M, Raju S, Stevens M, Boyle S, Park JS, Weirauch MT, Brent MR, Kopan R. SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers. Molecular Cell. 2015;9(4):685-697.

Demitrack ES, Gifford GB, Keeley TM, Carulli AJ, VanDussen KL, Thomas D, Giordano TJ, Liu Z, Kopan R, Samuelson LC. Notch signaling regulates gastric antral LGR5 stem cell function. EMBO J. 2015 Aug 12.

Liu Z, Brunskill E, Varnum-Finney B, Zhang C, Zhang A, Jay PY, Bernstein I, Morimoto M, Kopan R. The intracellular domains of Notch1 and 2 are functionally equivalent during development and carcinogenesis. Development. 2015;142:2452-2463.

Liu Z, Brunskill E, Boyle S, Chen S, Turkoz M, Guo Y, Grant R, Kopan R. Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity. Development. 2015 Mar 15;142(6):1193-202.

Demehri S, Yockey LJ, Visness CM, Jaffee KF, Turkoz A, Wood RA, O'Connor GT, Kattan M, Gern JE, Gergen PJ, Holtzman M, Bloomberg G, Kopan R. Circulating TSLP associates with decreased wheezing in non-atopic preschool children: Data from the URECA birth cohort. Clin Exp Allergy. 2014 Jun;44(6):851-7.

Zhao ZQ, Huo FQ, Jeffry J, Hampton L, Demehri S, Kim S, Liu XY, Barry DM, Wan L, Liu ZC, Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey JF Jr, Zhong J, Chen ZF. Chronic itch development in sensory neurons requires BRAF signaling pathways. J Clin Invest. 2013 Nov;123(11):4769-80.

Chillakuri CR, Sheppard D, Ilagan MX, Holt LR, Abbott F, Liang S, Kopan R, Handford PA, Lea SM. Structural analysis uncovers lipid-binding properties of notch ligands. Cell Rep. 2013 Nov 27;5(4):861-7.

Boyle SC1, Liu Z, Kopan R. Notch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development. Development. 2014 Jan;141(2):346-54.

Satpathy AT, Briseño CG, Lee JS, Ng D, Manieri NA, Kc W, Wu X, Thomas SR, Lee WL, Turkoz M, McDonald KG, Meredith MM, Song C, Guidos CJ, Newberry RD, Ouyang W, Murphy TL, Stappenbeck TS, Gommerman JL, Nussenzweig MC, Colonna M, Kopan R, Murphy KM. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol. 2013 Sep;14(9):937-48.

Yu Lan, PhD Member, Division of Plastic Surgery

Yu Lan, PhD, is interested in understanding the genetic basis and developmental mechanisms of structural birth defects. Specifically, Dr. Lan investigates the molecular pathways governing normal palate development in laboratory mice. Her ongoing investigations focus on delineating the molecular pathways involving these factors in palate development using a combination of genetic, embryological, and biochemical approaches.

Visit the Lan Lab.

513-803-7842 yu.lan@cchmc.org

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Yu Lan, PhD

Member, Division of Plastic Surgery

Academic Affiliations

Associate Professor, UC Department of Surgery

UC Department of Pediatrics

Phone 513-803-7842

Email yu.lan@cchmc.org

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Visit the Lan Lab.

Biography

Yu Lan, PhD, is interested in understanding the genetic basis and developmental mechanisms of structural birth defects. Specifically, Dr. Lan investigates the molecular pathways governing normal palate development in laboratory mice. Her ongoing investigations focus on delineating the molecular pathways involving these factors in palate development using a combination of genetic, embryological, and biochemical approaches.

PhD: University of Maine, Orono, ME.

Post-doc training: Wesleyan University, Middletown, CT; The Jackson Laboratory, Bar Harbor, ME.

Lan Y, Jia S, Jiang R. Molecular patterning of the mammalian dentition. Semin Cell Dev Biol. 2014 Jan-Feb;25-26: 61-70.

Liu H, Lan Y, Xu J, Chang CF, Brugmann SA, Jiang R. Odd-skipped related-1 controls neural crest chondrogenesis during tongue development. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18555-60.

Xu J, Liu H, Park JS, Lan Y, Jiang R. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis. Development. 2014 Apr;141(7):1442-52.

Zhou H, Zou S, Lan Y, Fei W, Jiang R, Hu J. Smad7 modulates TGFbeta signaling during cranial suture development to maintain suture patency. J Bone Miner Res. 2014 Mar;29(3):716-24.

Zhou J, Gao Y, Lan Y, Jia S, Jiang R. Pax9 regulates a molecular network involving Bmp4, Fgf10, Shh signaling and the Osr2 transcription factor to control palate morphogenesis. Development. 2013 Dec;140(23):4709-18.

Lan Y, Liu H, Ovitt CE, Jiang R. Generation of Osr1 conditional mutant mice. Genesis. 2011 May;49(5):419-22.

Gao Y, Lan Y, Liu H, Jiang R. The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation. Dev Biol. 2011 Apr 1;352(1):83-91.

Baek JA, Lan Y, Liu H, Maltby KM, Mishina Y, Jiang R. Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation. Dev Biol. 2011 Feb 15;350(2):520-31.

Chen J, Lan Y, Baek JA, Gao Y, Jiang R. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol. 2009 Oct 1;334(1):174–85.

Lan Y, Jiang R. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development. 2009 Apr;136(8):1387-96.

Richard A. Lang, PhD Director, Visual Systems Group

Richard A. Lang, PhD, has two major research interests. First, the lab is interested in mechanisms of signaling and morphogenesis in early eye development. Second, they investigate the role macrophages play in regulating vascularity during development and homeostasis.
Visit the Lang Lab.

513-636-2700 richard.lang@cchmc.org

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Richard A. Lang, PhD

Director, Visual Systems Group

Academic Affiliations

Professor, UC Department of Pediatrics

UC Department of Ophthalmology

Phone 513-636-2700

Fax 513-803-0740

Email richard.lang@cchmc.org

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Wnt ligands in tumorigenesis; vascular regression and tissue regeneration; lens induction and morphogenesis.

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BSc: Co-major in genetics and biochemistry, University of Melbourne, Australia, 1984 (with honors).

PhD: University of Melbourne, Australia, at the Ludwig Institute for Cancer Research under Drs. AR Dunn and TJ Gonda, 1988.

Postdoctoral Fellow: The G.W. Hooper Research Foundation, University of California, San Francisco under Dr. JM Bishop, 1989-92. Studied the role of the macrophage in developmentally programmed tissue remodeling.

Yeo EJ, Cassetta L, Qian BZ, Lewkowich I, Li JF, Stefater JA 3rd, Smith AN, Wiechmann LS, Wang Y, Pollard J, Lang RA. Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Res. 2014 Jun 1;74(11):2962-73.

Rao S, Chun C, Fan J, Kofron JM, Yang MB, Hegde RS, Ferrara N, Copenhagen DR, Lang RA. A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature. 2013;494(7436):243-6.

Stefater JA 3rd, Lewkowich I, Rao S, Mariggi G, Carpenter AC, Burr AR, Fan J, Ajima R, Molkentin JD, Williams BO, Wills-Karp M, Pollard JW, Yamaguchi T, Ferrara N, Gerhardt H, Lang RA. Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature. 2011 May 29;474(7352):511-5.

Chauhan BK, Lou M, Zheng Y, Lang RA. Balanced Rac1 and RhoA activities regulate cell shape and drive invagination morphogenesis in epithelia. PNAS. 2011 Nov 8;108(45):18289-94.

Plageman TF Jr, Chung MI, Lou M, Smith AN, Hildebrand JD, Wallingford JB, Lang RA. Pax6-dependent Shroom3 expression regulates apical constriction during lens placode invagination. Development. 2010 Feb;137(3):405-15.

Lobov IB, Rao S, Carroll TJ, Vallance JE, Ito M, Ondr JK, Kurup S, Glass DA, Patel MS, Shu W, Morrisey EE, McMahon AP, Karsenty G, Lang RA. Wnt7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature. 2005 Sep 15;437(7057):417-21.

Xinhua Lin, PhD

Xinhua Lin, PhD, is interested in cell-cell signaling mechanisms that control tissue patterning during development. His lab focuses on the role of heparan sulfate proteoglycans in morphogen distribution and signaling. The Lin Lab also studies the molecular mechanisms of Wnt signaling in development.

513-636-2144 xinhua.lin@cchmc.org

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Xinhua Lin, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-2144

Fax 513-636-4317

Email xinhua.lin@cchmc.org

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Understanding the mechanisms governing the regulation of cell-cell signaling by extracellular molecules that play essential roles in coordinating cell growth and differentiation; the role of heparan sulfate proteoglycans (HSPGs) in cell-cell signaling; identification of molecules that modulate the function of two key signaling molecules, Wnt/Wingless (Wg), Hedgehog (Hh).

Biography

Xinhua Lin, PhD, completed his doctoral work at the Washington University with Thomas. F. Deuel, where he studied the transcriptional regulation of platelet-derived growth factor A-chain gene. He then went to the Dr. Norbert Perrimon lab at Harvard Medical School, where he initiated his work on the role of heparan sulfate proteoglycan in cell-cell signaling in drosophila.

Dr. Lin has identified and characterized two mutations, sugarless and sulfateless, which occur in the genes that encode essential enzymes for the biosynthesis of heparin/heparin sulfate glycosaminoglycan (HSPG). Analyses of these mutants led to the demonstration that HSPGs play critical roles in the signaling activities of several growth factors including Wg, Hh and FGF. Dr. Lin further demonstrated that glypican members of HSPG play key roles in Wg signaling and the formation of Wg morphogen gradient. He became an assistant professor in April, 2000, at Cincinnati Children's Hospital Medical Center. His lab is interested in elucidating the molecular mechanisms of cell-cell signaling, focusing on the role of HSPG in signaling and the morphogen gradient formation of the Wg and Hh proteins.

BS: Hangchou University, Hangchou, P.R. China, 1984.

MS: Shanghai Institute of Cell Biology, Academia Sinica, P.R. China, 1987.

PhD: Washington University, St. Louis, MO, 1995.

Fellowship: Postdoctoral Research Fellow, Howard Hughes Medical Institute/Harvard Medical School, Cambridge, MA, 1995-2000.

You J, Belenkaya T, Lin X. Sulfated is a negative feedback regulator of wingless in Drosophila. Dev Dyn. 2011 Feb 8. doi: 10.1002/dvdy.22562.

Deng J, Deng L, Su S, Zhang M, Lin X, Wei L, Minai AA, Hassett DJ, Lu LJ. Investigating the predictability of essential genes across distantly related organisms using an integrative approach. Nucleic Acids Res. 2011 Feb 1;39(3):795-807.

Yan D, Wu Y, Yang Y, Belenkaya TY, Tang X, Lin X. The cell-surface proteins Dally-like and Ihog differentially regulate Hedgehog signaling strength and range during development. Development. 2010 Jun;137(12):2033-44.

Yan D, Lin X. Shaping morphogen gradients by proteoglycans. Cold Spring Harb Perspect Biol. 2009 Sep;1(3):a002493. Review.

Yan D, Wu Y, Feng Y, Lin SC, Lin X. The core protein of glypican Dally-like determines its biphasic activity in wingless morphogen signaling. Dev Cell. 2009 Oct;17(4):470-81.

Lin X, Pittman J, Clarke B. Information Conversion, Effective Samples, and Parameter Size. IEEE Trans Inf Theory. 2007 Dec;53(12):4438-4456.

Chen Y, Guo JJ, Healy DP, Lin X, Patel NC. Risk of hepatotoxicity associated with the use of telithromycin: a signal detection using data mining algorithms. Ann Pharmacother. 2008 Dec;42(12):1791-6.

He F, Wen Y, Deng J, Lin X, Lu LJ, Jiao R, Ma J. Probing intrinsic properties of a robust morphogen gradient in Drosophila. Dev Cell. 2008 Oct;15(4):558-67.

Yan D, Lin X. Opposing roles for glypicans in Hedgehog signalling. Nat Cell Biol. 2008 Jul;10(7):761-3.

Belenkaya TY, Wu Y, Tang X, Zhou B, Cheng L, Sharma YV, Yan D, Selva EM, Lin X. The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network. Dev Cell. 2008 Jan;14(1):120-31.

Qing Richard Lu, PhD Beatrice C. Lampkin endowed Chair in Cancer Epigenetics

Qing Richard Lu, PhD, and his lab study the transcriptional and signaling regulatory networks that control gliogenesis (oligodendrocyte, astrocyte and Schwann cell), brain cancer stem/initiating cell growth and myelinogenesis. Dr. Lu lab utilizes transgenic and gene targeting mouse models to understand the molecular mechanisms underlying demyelinating diseases and brain tumorigenesis and to develop new therapies for neurodegenerative diseases and brain cancers.

Visit the Lu Lab.

513-636-7684 richard.lu@cchmc.org

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Qing Richard Lu, PhD

Beatrice C. Lampkin endowed Chair in Cancer Epigenetics

Scientific Director, Brain Tumor Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7684

Fax 513-636-3549

Email richard.lu@cchmc.org

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Visit the Lu Lab.

BS: Peking Normal University, Beijing, China, 1988.

MS: Rutgers University, Piscataway, NJ, 1993.

PhD: Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, 1997.

Postdoctoral Fellow: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 1997-2002.

Wu LMN, Deng Y, Wang J, Zhao C, Wang JJ, Rao R, Xu L, Zhou W, Choi K, Rizvi TA. Remke M, Rubin JB, Johnson R, Carroll T, Stemmer-Rachamimov AO, Wu J, Zheng Y, Xin M, Ratner N, Lu QR. Programming of Schwann Cells by Lats1/2-TAZ/YAP Signaling Drives Malignant Peripheral Nerve Sheath Tumorigenesis. Cancer Cell. 2018;33:1-17.

He X, Zhang L, Queme LF, Liu X, Lu A, Waclaw R, Dong X, Zhou W, Kidd G, Yoon SO, Buonanno A, Rubin JB, Xin M, Nave KA, Trapp BD, Jankowski MP, Lu QR. A Histone Deacetylase 3-Dependent Pathway Delimits Peripheral Myelin Growth and Functional Regeneration. Nat Medicine. 2018.

Deng Y*, Wu L*, Bai* S, Zhao C, Wang H, Wang J, Xu L, Zhou W, Xin M, Lu QR. A Reciprocal Regulatory Loop Between TAZ/YAP and G protein Gαs Regulates Schwann Cell Proliferation and Differentiation. Nature Communications. 2017;8:15161.

He D, Wang J, Lu Y, Deng Y, Zhao C, Xu L, Chen Y, Hu Y, Zhou W, Lu QR. lncRNA Functional Networks in Oligodendrocytes Reveal Stage-Specific Myelination Control by an lncOL1/Suz12 Complex in the CNS. Neuron. 2017 Jan 18;93(2):362-378.

Wu LM, Wang J, Conidi A, Zhao C, Wang H, Ford Z, Zhang L, Zweier C, Ayee BG, Maurel P, Zwijsen A, Chan JR, Jankowski MP, Huylebroeck D, Lu QR. Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination. Nat Neurosci. 2016 Aug;19(8):1060-72.

Lu F, Chen Y, Zhao C, Wang H, He D, Xu L, Wang J, He X, Deng Y, Lu EE, Liu X, Verma R, Bu H, Drissi R, Fouladi M, Stemmer-Rachamimov AO, Burns D, Xin M, Rubin JB, Bahassi EM, Canoll P, Holland EC, Lu QR. Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma. Cancer Cell. 2016; 9;29(5):669-83.

He D, Marie C, Zhao C, Kim B, Wang J, Deng Y, Clavairoly A, Frah M, Wang H, He X, Hmidan H, Jones BV, Witte D, Zalc B, Zhou X, Choo DI, Martin DM, Parras C, Lu QR. Chd7 Cooperates with Sox10 and Regulates the Onset of CNS Myelination and Remyelination. Nature Neuroscience. 2016 May;19(5):678-89. 

Zhang L*, He X*, Liu L, Jiang M, Zhao C, Wang H, He D, Zheng T, Zhou X, Hassan A, Ma Z, Xin M, Sun Z, Lazar MA, Goldman SA, Olson EN, Lu QR. Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch. Developmental Cell. 2016 Feb 8;36(3):316-30.

He X, Zhang L, Chen Y, Remke M, Shih D, Lu F, Wang H, Deng Y, Yu Y, Xia Y, Wu X, Ramaswamy V, Hu T, Wang F, Zhou W, Burns DK, Kim SH, Kool M, Pfister S, Weinstein LS, Pomeroy S, Gilbertson R, Rubin JB, Hou Y, Wechsler-Reya R, Taylor MD, Lu QR. The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog driven Medulloblastoma. Nature Medicine. 2014 Sep;20(9):1035-42.

Yu Y, Chen Y, Kim B, Wang H, Zhao C, He X, Liu L, Liu W, Wu, LM, Mao M, Chan JR, Wu J, Lu QR. Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell. 2013 Jan 17;152(1-2):248–261.

Grants

Molecular Mechanisms of Oligodendrocyte Differentiation and Myelination. Principal Investigator. National Institutes of Health (NINDS). Sep 2015-Aug 2020. 1R01NS072427.

Chromatin Remodeling Control of CNS Myelination and Remyelination. Principal Investigator. National Institutes of Health (NINDS). Apr 2012–Mar 2020. 1R01NS075243-01.

A Novel Model of Medulloblastoma to Define Cancer Pathways and Molecular Targets. Principal Investigator. National Institutes of Health (NINDS). Apr 2012–Mar 2018. 1R01NS078092.

Christopher N. Mayhew, PhD Co-Director, Pluripotent Stem Cell Facility

Christopher N. Mayhew, PhD, is co-director of the Pluripotent Stem Cell Facility. His lab functions as a core facility providing access for Cincinnati Children's / University of Cincinnati investigators to highly quality controlled human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells. In addition, the lab provides training in the culture and manipulation of human pluripotent stem cells to investigators.

513-636-3744 christopher.mayhew@cchmc.org

Masato Nakafuku, MD, PhD Ohio Eminent Scholar

Masato Nakafuku, MD, PhD, is focused on the development and regeneration of the mammalian central nervous system (CNS). He is seeking to understand the molecular mechanisms underlying normal development of the CNS and is also interested in applying advancement of knowledge on neural development for developing novel therapeutic strategies to cure neurological diseases.
Visit the Nakafuku Lab.

513-636-9389 masato.nakafuku@cchmc.org

Masato Nakafuku, MD, PhD

Ohio Eminent Scholar

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-9389

Fax 513-636-4317

Email masato.nakafuku@cchmc.org

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Development and regeneration of the central nervous system (CNS); therapeutic strategies for neurological diseases

Visit the Nakafuku Lab.

PhD: Graduate School of Medical Sciences, University of Tokyo, Tokyo, Japan, 1988.

MD: The University of Kanazawa School of Medicine, Japan, 1984.

Pei Z, Wang B, Chen G, Nagao M, Nakafuku M, Campbell K. Homeobox genes Gsx1 and Gsx2 differentially regulate telencephalic progenitor maturation. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1675-80.

Shereen A, Nemkul N, Yang D, Adhami F, Dunn RS, Hazen ML, Nakafuku M, Ning G, Lindquist DM, Kuan CY. Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke. J Cereb Blood Flow Metab. 2010 Dec 8.

Nagao M, Campbell K, Burns K, Kuan CY, Trumpp A, Nakafuku M. Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19ARF-p53 pathway. J Cell Biol. 2008 Dec 29;183(7):1243-57.

Sugimori M, Nagao M, Parras CM, Nakatani H, Lebel M, Guillemot F, Nakafuku M. Ascl1 is required for oligodendrocyte development in the spinal cord.Development. 2008 Apr;135(7):1271-81.

Nakafuku M, Nagao M, Grande A, Cancelliere A. Revisiting neural stem cell identity. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):829-30.

Kim HJ, Sugimori M, Nakafuku M, Svendsen CN. Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1. Exp Neurol. 2007 203:394-405.

Nagao M, Sugimori M, Nakafuku M. Cross talk between notch and growth factor/cytokine signaling pathways in neural stem cells. Mol Cell Biol. 2007 Jun;27(11):3982-94.

Parras CM, Hunt C, Sugimori M, Nakafuku M, Rowitch D, Guillemot F. The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes. J Neurosci. 2007 27:4233-4242.

Sugimori M, Nagao M, Bertrand N, Parras CM, Guillemot F, Nakafuku M. Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord. Development. 2007 Apr;134(8):1617-29.

Ohori Y, Yamamoto S, Nagao M, Sugimori M, Yamamoto N, Nakamura K, Nakafuku M. Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord. J Neurosci. 2006 Nov 15;26(46):11948-60.

Takahisa Nakamura, PhD

Takahisa Nakamura, PhD, research goal is to address questions concerning why and how inflammatory responses are initiated, coordinated, and thus involved in the development of obesity-induced metabolic diseases.

Visit the Nakamura Lab.

513-636-4744 takahisa.nakamura@cchmc.org

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Takahisa Nakamura, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-4744

Email takahisa.nakamura@cchmc.org

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RNA-related inflammation in obesity and metabolic diseases

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Biography

Dr. Nakamura received his PhD from the University of Tokyo in 2003. He completed postdoctoral training in the laboratory of Dr. Gökhan S. Hotamisligil at Harvard School of Public Health in 2013, followed by his faculty appointment at Cincinnati Children's Hospital Medical Center within the UC Department of Pediatrics in 2013.

PhD: University of Tokyo, 2003.

Postdoctoral Fellow: University of Tokyo, 2003-2006.

Research Fellow: Harvard University, 2006-2010.

Research Associate: Harvard University, 2010-2013.

Nakamura T, Arduini A, Baccaro B, Furuhashi M, Hotamisligil GS. Small molecule inhibitors of PKR improve glucose homeostasis in obese, diabetic mice. Diabetes. 2014 Feb;63(2):526-34.

Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ. Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012 Aug 20;488(7413):670-4.

Morita M. Oike Y, Nagashima T, Kadomatsu T, Tabata M, Suzuki T, Nakamura T, Yoshida N, Okada M, Yamamoto T. Obesity resistance and increased hepatic expression of catabolism-related mRNAs in Cnot3(+/-) mice. EMBO J. 2011 Sep 6;30(22):4678-4691.

Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, Gorgun CZ, Hotamisligil GS. Double-stranded RNA-dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis. Cell. 2010 Feb 5;140(3):338-48.

Yoneda M, Suzuki T, Nakamura T, Ajima R, Yoshida Y, Kakuta S, Sudo K, Iwakura Y, Shibutani M, Mitsumori K, Yokota J, Yamamoto T. Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma. Cancer Sci. 2009 Feb;100(2):224-232.

Ajima R, Akiyama T, Usui M, Yoneda M, Yoshida Y, Nakamura T, Minowa O, Noda M, Tanaka S, Noda T, Yamamoto T. Osteoporotic bone formation in mice lacking tob2; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation. FEBS Lett. 2008 Apr 16;582(9):1313-8.

Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T. Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth. Mol Cell Biol. 2007 Jul;27(13):4980-90.

Nakamura T, Yao R, Ogawa T, Suzuki T, Ito C, Tsunekawa N, Inoue K, Ajima R, Miyasaka T, Yoshida Y, Ogura A, Toshimori K, Noce T, Yamamoto T, Noda T. Oligoasthenoteratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nat Genet. 2004 May;36(5):528-33.

Kimura H*, Nakamura T*, Ogawa T, Tanaka S, Shiota K. Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways. Nucleic Acids Res. 2003 Jun 15;31(12):3101-13. *These authors contributed equally to this work.

Yoshida Y*, Nakamura T*, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, Miyasaka T, Yoshida EH, Umemori H, Kunisaki RK, Tani K, Ishii S, Mori S, Suganuma M, Noda T, Yamamoto T. Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes Dev. 2003 May 15;17(10):1201-6. *These authors contributed equally to this work.

Grants

Analysis of pathogenic double-stranded RNA in chronic inflammatory diseases. Principal Investigator. Japan Science and Technology Agency, PRESTO. Feb 2013–Mar 2016.

Satoshi H. Namekawa, PhD

Satoshi H. Namekawa, PhD, examines the mechanisms and evolution of epigenetic events during mammalian reproduction, using a male germ cell model.
Visit the Namekawa Lab.

513-803-1377 satoshi.namekawa@cchmc.org

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Satoshi H. Namekawa, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1377

Fax 513-803-1160

Email satoshi.namekawa@cchmc.org

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The long-term goal of the Namekawa laboratory is to reveal and fully explain epigenetic mechanisms in germ cells and stem cells, with an emphasis on how germline identity is defined and the recovery of totipotency after fertilization—mechanisms that are ultimately responsible for the perpetuity of life. Specifically, the laboratory focuses on how the epigenome is preset, or poised, in stem cells for gene regulation in subsequent stages of differentiating germ cells, thereby ensuring stage-specific transcriptional regulation in the context of germ cell development and aging. Illumination of these mechanisms will explain the central identity of the germline and address how epigenetic information is transmitted across generations. Further, the laboratory aims to identify mechanisms by which the integrity of the germline is ensured, as this is key to understanding how the integrity of life is ensured, an essential and longstanding question in biology. Another area of focus is the epigenetic regulation of sex chromosomes in germ cell development, with an emphasis on how the sex chromosomes specifically function for reproduction.

Visit the Namekawa Lab.

Biography

Dr. Namekawa received his PhD from Tokyo University of Science in 2005. He completed postdoctoral training in the laboratory of Dr. Jeannie T. Lee at Massachusetts General Hospital and Harvard Medical School in 2009, and attained his faculty appointment at Cincinnati Children's Hospital Medical Center in 2009. He received the Basil O’Connor Award from March of Dimes Foundation in 2011, the New Investigator Award from the Society for the Study of Reproduction in 2015, and the Research Achievement Award from Cincinnati Children’s Hospital Medical Center in 2016.

PhD: Tokyo University of Science, Japan, 2005.

BS: Tokyo University of Science, Japan, 2000.

Maezawa S, Hasegawa K, Yukawa M, Kubo N, Sakashita A, Alavattam KG, Sin HS, Kartashov AV, Sasaki H, Barski A, Namekawa SH. Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline. Proc Natl Acad Sci U S A. 2018 May 8;115(19):4957-4962.

Adams SR, Maezawa S, Alavattam KG, Abe H, Sakashita A, Shroder M, Broering TJ, Sroga Rios J, Thomas MA, Lin X, Price CM, Barski A, Andreassen PR, Namekawa SH. RNF8 and SCML2 cooperate to regulate ubiquitination and H3K27 acetylation for escape gene activation on the sex chromosomes. PLoS Genet. 2018 Feb 20;14(2):e1007233.

Abe H, Alavattam KG, Kato Y, Castrillon DH, Pang Q, Andreassen PR, Namekawa SH. CHEK1 coordinates DNA damage signaling and meiotic progression in the male germline of mice. Hum Mol Genet. 2018 Apr 1;27(7):1136-1149.

Maezawa S, Yukawa M, Alavattam KG, Barski A, Namekawa SH. Dynamic reorganization of open chromatin underlies diverse transcriptomes during spermatogenesis. Nucleic Acids Res. 2018 Jan 25;46(2):593-608.

Maezawa S, Hasegawa K, Yukawa M, Sakashita A, Alavattam KG, Andreassen PR, Vidal M, Koseki H, Barski A, Namekawa SH. Polycomb directs timely activation of germline genes in spermatogenesis. Genes Dev. 2017 Aug 15;31(16):1693-1703.

Alavattam KG, Kato Y, Sin HS, Maezawa S, Kowalski IJ, Zhang F, Pang Q, Andreassen PR, Namekawa SH. Elucidation of the Fanconi Anemia Protein Network in Meiosis and Its Function in the Regulation of Histone Modifications. Cell Rep. 2016 Oct 18;17(4):1141-1157.

Hasegawa K, Sin HS, Maezawa S, Broering TJ, Kartashov AV, Alavattam KG, Ichijima Y, Zhang F, Bacon WC, Greis KD, Andreassen PR, Barski A, Namekawa SH. SCML2 establishes the male germline epigenome through regulation of histone H2A ubiquitination. Dev Cell. 2015 Mar 9;32(5):574-88.

Sin HS, Barski A, Zhang F, Kartashov AV, Nussenzweig A, Chen J, Andreassen PR, Namekawa SH. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in postmeiotic spermatids. Genes Dev. 2012 Dec 15:26(24)2737-2748.

Sin HS, Ichijima Y, Koh E, Namiki M, Namekawa SH. Human post meiotic sex chromatin and its impact on sex chromosome evolution. Genome Res. 2012 May;22(5):827-36.

Ichijima, Y, Ichijima M, Lou Z, Nussenzweig A, Camerini-Otero RD, Chen J, Andreassen PR, Namekawa SH. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes Dev. 2011 May 1;25(9):959-71.

Ertugrul M. Ozbudak, PhD

Ertugrul M. Ozbudak, PhD, aspires to achieve a systems-level understanding of robust spatiotemporal pattern formation (e.g. rhythmic segmentation of somites) and cell fate determination by integrating quantitative experiments with computational modeling. These efforts aim to provide a mechanistic understanding of congenital diseases.

513-803-2607 ertugrul.ozbudak@cchmc.org

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Ertugrul M. Ozbudak, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-2607

Email ertugrul.ozbudak@cchmc.org

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Segmentation of vertebral column; pattern formation; cell differentiation; systems biology; computational modeling

Visit the Ozbudak Lab

Biography

Ertugrul M. Ozbudak, PhD's, overriding interest is to achieve a quantitative understanding of complex biological systems by integrating systems-level biological experimentation with mathematical modeling. He has worked on different biological phenomena, such as: stochasticity and multistability in gene expression, cell polarization and symmetry breaking, entrainment of gene expression oscillations, gene regulatory networks and analysis of transcriptome during muscle differentiation and vertebral segmentation. He has utilized genome-wide techniques, single-cell microscopy measurements, time-resolved perturbation experiments, mathematical modeling and computational simulations to accomplish these projects.

Stochastic mechanisms are common in biological systems. His earlier PhD studies investigated the effects of these microscopic fluctuations (biochemical noise) on macroscopic variations in gene expression (phenotypic noise). His follow-up studies showed that cells could utilize positive feedback loops to exploit the stochastic gene expression to achieve bistability at the population level. These work were among the first multidisciplinary studies focused on stochastic gene expression and triggered the blossoming of the “stochastic gene expression” field.

Afterwards, Dr. Ozbudak investigated the systems-level properties of the vertebrate segmentation clock. He has performed computational modeling and time-resolved perturbation experiments to demonstrate that Notch signaling keeps the oscillations of neighboring cells synchronized. The period of the segmentation clock oscillations gets longer as cells are displaced along the posterior-to-anterior axis, which results in traveling waves of clock gene expression sweeping in the unsegmented tissue. By combining molecular-level computational modeling and quantitative experimentation, they showed that a gradient of gene expression time-delays along the axis underlies the traveling segmentation clock waves.

BS: Physics Department, Bogazici University, Istanbul, Turkey, 1999.

PhD: Physics Department, Massachusetts Institute of Technology Cambridge, MA, 2004.

Postdoctoral Research Fellow: Cancer Research UK (now Francis Crick Institute), London, UK, 2007.

Senior Research Associate: Stowers Institute for Medical Research, Kansas City, MO, 2009.

Ay A, Sperlea A, Devakanmalai GS, Holland J, Knierer S, Sangervasi S, Özbudak EM. Gradients of gene expression time-delays set the pace of the traveling segmentation clock waves. Development. 2014;141(21):4158-4167.

Ay A, Knierer S, Sperlea A, Holland J, Özbudak EM. Short-lived Her Proteins Drive Robust Synchronized Oscillations in the Zebrafish Segmentation Clock. Development. 2013;140(15):3244-3253.

Devakanmalai GS, Zumrut HE, Özbudak EM. Cited3 activates Mef2c to control muscle cell differentiation and survival. Biology Open. 2013;2:505-514.

Özbudak EM, Tassy O, Pourquié O. Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation. Proc Natl Acad Sci USA. 2010;107(9):4224-9.

Gomez C, Özbudak EM, Wunderlich J, Baumann D, Lewis J, Pourquié O. Control of segment number in vertebrate embryos. Nature. 2008;454(7202):335-339.

Özbudak EM, Lewis J. Notch signalling synchronises the zebrafish somite segmentation clock but is not needed to create somite boundaries. PLoS Genetics. 2008;4(2):e15.

Giudicelli F, Özbudak EM, Lewis J. Setting the Tempo in Development: an Investigation of the Zebrafish Somite Clock Mechanism. PLoS Biology. 2007;5(6):e150.

Özbudak EM, Becskei A, van Oudenaarden A. A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization. Dev Cell. 2005;9(4):565-571.

Özbudak EM, Thattai M, Lim HN, Shraiman BI, Van Oudenaarden A. Multistability in the lactose utilization network of Escherichia coli. Nature. 2004;427(6976):737-740.

Özbudak EM, Thattai M, Kurtser I, Grossman AD, van Oudenaarden A. Regulation of noise in the expression of a single gene. Nature Genetics. 2002;31(1):69-73.

Grants

Regulatory Mechanisms Governing Vertebral Segmentation. Principal Investigator. National Institutes of Health. Sep 2014-Jun 2019. #R01 GM111987.

Elucidating the Mechanism of Precision in Vertebral Segmentation. Principal Investigator. National Institutes of Health. Apr 2017–Mar 2021. #R01 GM122956.

Joo-Seop Park, PhD

Joo-Seop Park, PhD, is interested in understanding how progenitor cells maintain their multi-potent status and how they differentiate into different types of cells during organogenesis of the mammalian kidney and bladder. His lab studies transcriptional and epigenetic controls of cis-regulatory modules that act downstream of various signaling pathways.

Visit the Park Lab.

513-803-7871 pedsurology@cchmc.org

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Joo-Seop Park, PhD

Academic Affiliations

Assistant Professor, UC Department of Surgery

Phone 513-803-7871

Email pedsurology@cchmc.org

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Molecular biology; genetics.

Visit the Park Lab.

Biography

Joo-Seop Park, PhD, is an assistant professor in the Divisions of Pediatric Urology and Developmental Biology at Cincinnati Children's Hospital Medical Center. He received his bachelor's in pharmacy from Seoul National University in Seoul, South Korea. He subsequently studied the regulation of gene transcription with Dr. Jeffrey W. Roberts at Cornell University in Ithaca, NY where he obtained his doctorate in molecular biology and genetics in 2004. Dr. Park then went on to postdoctoral training with Dr. Andrew P. McMahon at Harvard University where he was awarded fellowships from the National Kidney Foundation and the Charles King Trust to study mammalian kidney development.

Dr. Park is interested in understanding how progenitor cells maintain their multi-potent status and how they differentiate into different types of cells during organogenesis of the mammalian kidney and bladder. His lab studies transcriptional and epigenetic controls of cis-regulatory modules that act downstream of various signaling pathways.

PhD: Molecular Biology, Cornell University.

Lo YH, Chung E, Li Z, Wan YW, Mahe MM, Chen MS, Noah TK, Bell KN, Yalamanchili HK, Klisch TJ, Liu Z, Park JS, Shroyer NF. Transcriptional Regulation by ATOH1 and its Target SPDEF in the Intestine. Cell Mol Gastroenterol Hepatol. 2017;3(1):51-71.

Cotton JL, Li Q, Ma L, Park JS, Wang J, Ou J, Zhu LJ, Ip YT, Johnson RL, Mao J. YAP/TAZ and Hedgehog Coordinate Growth and Patterning in Gastrointestinal Mesenchyme. Dev Cell. 2017;43(1):35-47 e4.

Chung E, Deacon P, Park JS. Notch is required for the formation of all nephron segments and primes nephron progenitors for differentiation. Development. 2017;144(24):4530-9.

Warrick JI, Walter V, Yamashita H, Chung E, Shuman L, Amponsa VO, Zheng Z, Chan W, Whitcomb TL, Yue F, Iyyanki T, Kawasawa YI, Kaag M, Guo W, Raman JD, Park JS, DeGraff DJ. FOXA1, GATA3 and PPAR Cooperate to Drive Luminal Subtype in Bladder Cancer: A Molecular Analysis of Established Human Cell Lines. Sci Rep. 2016;6:38531.

Liu X, Li H, Rajurkar M, Li Q, Cotton JL, Ou J, Zhu LJ, Goel HL, Mercurio AM, Park JS, Davis RJ, Mao J. Tead and AP1 Coordinate Transcription and Motility. Cell reports. 2016;14(5):1169-80.

Chung E, Deacon P, Marable S, Shin J, Park JS. Notch signaling promotes nephrogenesis by downregulating Six2. Development. 2016;143(21):3907-13.

Xu J, Liu H, Park JS, Lan Y, Jiang R. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis. Development. 2014;141:1442-1452.

Brunskill EW, Park JS, Chung E, Chen F, Magella B, Potter SS. Single cell dissection of early kidney development: multilineage priming. Development. 2014;141, 3093-3101.

Wang J, Park JS, Wei Y, Rajurkar M, Cotton JL, Fan Q, Lewis BC, Ji H, Mao J. TRIB2 acts downstream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPalpha function. Mol Cell. 2013;51:211-225.

Park JS, Ma W, O'Brien LL, Chung E, Guo JJ, Cheng JG, Valerius MT, McMahon JA, Wong WH, McMahon AP. Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev Cell. 2012;23:637-651.

S. Steven Potter, PhD

S. Steven Potter, PhD, is interested in kidney and craniofacial development and disease. He uses a combination of laser capture microdissection, microarrays, and next generation sequencing, applied to both mouse models and human biopsy disease samples.
Visit the Potter Lab.

513-636-4850 steve.potter@cchmc.org

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S. Steven Potter, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-4850

Fax 513-636-4317

Email steve.potter@cchmc.org

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Kidney development and disease; Hox genes; craniofacial development; creation of an atlas of global gene expression patterns in the multiple compartments of the developing kidney; analysis of perturbed gene expression patterns in the kidney glomeruli of patients with focal segmental glomerulosclerosis; craniofacial development using mutant mice, laser capture microdissection, next generation sequencing, and microarrays; recombineering to target multiple Hox genes at once

Visit the Potter Lab.

BA: University of California, Los Angeles (UCLA), CA, 1971.

PhD: University of North Carolina, Chapel Hill, NC, 1976.

Postdoctoral Fellowship: Harvard Medical School, Boston, MA, 1976-1978.

Potter SS, Brunskill EW, Patterson LT. Defining the genetic blueprint of kidney development. Pediatr Nephrol. 2011 Feb 19.

Potter SS, Brunskill EW, Patterson LT. Microdissection of the gene expression codes driving nephrogenesis. Organogenesis. 2010 Oct-Dec;6(4):263-9.

Brunskill EW, Potter SS. Gene expression programs of mouse endothelial cells in kidney development and disease. PLoS One. 2010 Aug 10;5(8):e12034.

Georgas K, Rumballe B, Valerius MT, Chiu HS, Thiagarajan RD, Lesieur E, Aronow BJ, Brunskill EW, Combes AN, Tang D, Taylor D, Grimmond SM, Potter SS, McMahon AP, Little MH. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. Dev Biol. 2009 332(2):273-86.

Brunskill EW, Aronow BJ, Georgas K, Rumballe B, Valerius MT, Aronow J, Kaimal V, Jegga AG, Yu J, Grimmond S, McMahon AP, Patterson LT, Little MH, Potter SS. Atlas of gene expression in the developing kidney at microanatomic resolution. Dev Cell. 2008 Nov;15(5):781-91. Erratum in: Dev Cell. 2009 Mar;16(3):482. Yu, Jing [added].

Adam M, Murali B, Glenn NO, Potter SS. Epigenetic inheritance based evolution of antibiotic resistance in bacteria. BMC Evol Biol. 2008 Feb 18;8:52.

Bennett MR, Czech KA, Arend LJ, Witte DP, Devarajan P, Potter SS. Laser capture microdissection-microarray analysis of focal segmental glomerulosclerosis glomeruli. Nephron Exp Nephrol. 2007;107(1):e30-40.

Potter SS, Hartman HA, Kwan KM, Behringer RR, Patterson LT. Laser capture-microarray analysis of Lim1 mutant kidney development. Genesis. 2007 Jul;45(7):432-9.

Song N, Schwab KR, Patterson LT, Yamaguchi T, Lin X, Potter SS, Lang RA. pygopus 2 has a crucial, Wnt pathway-independent function in lens induction. Development. 2007 May;134(10):1873-85.

Schwab KR, Patterson LT, Hartman HA, Song N, Lang RA, Lin X, Potter SS. Pygo1 and Pygo2 roles in Wnt signaling in mammalian kidney development. BMC Biol. 2007 Apr 10;5:15.

Schwab K, Hartman HA, Liang HC, Aronow BJ, Patterson LT, Potter SS. Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development. Dev Biol. 2006 May 15;293(2):540-54.

Juan Sanchez Gurmaches, PhD

The long-term objective of their research program is to elucidate the developmental and metabolic mechanisms that control adipocyte functions. They are currently working on (1) the developmental and metabolic basis of adipocyte heterogeneity; (2) how metabolic and signaling pathways impact adipose tissue distribution and function; (3) the genetic diversity of lipodystrophy disorders to obtain new insights into adipose tissue biology.

513-636-4001 juan.sanchezgurmaches@cchmc.org

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Juan Sanchez Gurmaches, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-4001

Email juan.sanchezgurmaches@cchmc.org

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Adipocytes; brown and white fat; animal models; adipocyte development and heterogeneity; insulin signaling; animal models

BS: University of Barcelona, Catalunya, Spain, 2005.

PhD: University of Barcelona, Catalunya, Spain, 2010.

Sanchez-Gurmaches J, Hung CM, Guertin DA. Emerging Complexities in Adipocyte Origins and Identity. Trends Cell Biol. 2016 May;26(5):313-26.

Tang Y, Wallace M, Sanchez-Gurmaches J, Hsiao WY, Li H, Lee PL, Vernia S, Metallo CM, Guertin DA. Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism. Nat Commun. 2016 Apr 21;7:11365.

Sanchez-Gurmaches J, Hsiao WY, Guertin DA. Highly Selective In Vivo Labeling of Subcutaneous White Adipocyte Precursors with Prx1-Cre. Stem Cell Reports. 2015 Apr 14;4(4):541-50.

Sanchez-Gurmaches J, Guertin DA. mTORC1 gRABs the Golgi. Cancer Cell. 2014 Nov 10;26(5):601-3.

Sanchez-Gurmaches J, Guertin DA. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat Commun. 2014 Jun 19;5:4099.

Sanchez-Gurmaches J, Guertin DA. Adipocyte lineages: tracing back the origins of fat. Biochim Biophys Acta. 2014 Mar;1842(3):340-51.

Hung CM, Calejman CM, Sanchez-Gurmaches J, Li H, Clish CB, Hettmer S, Wagers AJ, Guertin DA. Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease. Cell Rep. 2014 Jul 10;8(1):256-71.

Sanchez-Gurmaches J, Hung CM, Sparks CA, Tang Y, Li H, Guertin DA. PTEN Loss in the Myf5 Lineage Redistributes Body Fat and Reveals Subsets of White Adipocytes that Arise from Myf5 Precursors. Cell Metab. 2012 Sep 5;16(3):348-62.

Rolf W. Stottmann, PhD

Rolf W. Stottmann, PhD, is a developmental geneticist with an interest in using animal models to understand the genetic basis of human congenital defects. His lab is using both forward and reverse genetics to identify novel loci required for normal development. Further studies are then done to study the underlying molecular mechanism(s) leading to the defect. Specific areas of interest are cortical neuron development and craniofacial genetics.
Visit the Stottmann Lab.

513-636-7136 rolf.stottmann@cchmc.org

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Rolf W. Stottmann, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-7136

Email rolf.stottmann@cchmc.org

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Developmental neurobiology; genetics; animal models of human congenital defects

Visit the Stottmann Lab.

BS: University of Maryland, College Park, MD, 1995.

MS: University of Maryland, College Park, MD, 1997.

PhD: Duke University School of Medicine, Durham, NC, 2004.

Postdoctoral Training: Brigham & Women’s Hospital; Harvard Medical School.

Visit the Takebe Lab and Visit the Takebe Lab at Cincinnati Children's Hospital Medical Center.

Abdelhamed Z, Vuong SM, Hill L, Shula C, Timms A, Beier D, Campbell K, Mangano FT, Stottmann RW, Goto J. A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice. Development. 2018 Jan 9;145(1).

Driver AM, Shumrick C, Stottmann RW. Ttc21b Is Required in Bergmann Glia for Proper Granule Cell Radial Migration. J Dev Biol. 2017 Dec 19;5(4).

DiStasio A, Driver A, Sund K, Donlin M, Muraleedharan RM, Pooya S, Kline-Fath B, Kaufman KM, Prows CA, Schorry E, Dasgupta B, Stottmann RW. Copb2 is essential for embryogenesis and hypomorphic mutations cause human microcephaly. Hum Mol Genet. 2017 Dec 15;26(24):4836-4848.

Li Z, Peng Y, Hufnagel RB, Hu YC, Zhao C, Queme LF, Khuchua Z, Driver AM, Dong F, Lu QR, Lindquist DM, Jankowski MP, Stottmann RW, Kao WWY, Huang T. Loss of SLC25A46 causes neurodegeneration by affecting mitochondrial dynamics and energy production in mice. Hum Mol Genet. 2017 Oct 1;26(19):3776-3791.

Schock EN, Struve JN, Chang CF, Williams TJ, Snedeker J, Attia AC, Stottmann RW, Brugmann SA. A tissue-specific role for intraflagellar transport genes during craniofacial development. PLoS One. 2017 Mar 27;12(3):e0174206.

Snedeker J, Schock EN, Struve JN, Chang CF, Cionni M, Tran PV, Brugmann SA, Stottmann RW. Unique spatiotemporal requirements for intraflagellar transport genes during forebrain development. PLoS One. 2017 Mar 14;12(3):e0173258.

Stottmann RW, Driver A, Gutierrez A, Skelton MR, Muntifering M, Stepien C, Knudson L, Kofron M, Vorhees CV, Williams MT. A heterozygous mutation in tubulin, beta 2B ( Tubb2b ) causes cognitive deficits and hippocampal disorganization. Genes Brain Behav. 2017 Feb;16(2):250-259.

Gelineau-Morel R, Lukacs M, Weaver KN, Hufnagel RB, Gilbert DL, Stottmann RW. Congenital Cataracts and Gut Dysmotility in a DYNC1H1 Dyneinopathy Patient. Genes (Basel). 2016 Oct 14;7(10).

Go DE, Stottmann RW. The Impact of CRISPR/Cas9-Based Genomic Engineering on Biomedical Research and Medicine. Curr Mol Med. 2016;16(4):343-52.

Driver AM, Kratz LE, Kelley RI, Stottmann RW. Altered cholesterol biosynthesis causes precocious neurogenesis in the developing mouse forebrain. Neurobiol Dis. 2016 Feb 24;91:69-82.

Saulius Sumanas, PhD

Saulius Sumanas, PhD, utilizes zebrafish as a model system to study molecular mechanisms of the embryonic vasculature formation.
Visit the Sumanas Lab.

513-803-0435 saulius.sumanas@cchmc.org

Takanori Takebe, MD

Takanori Takebe, MD, investigates: 1. The deductive development of a complex human organoid model, 2. The multidisciplinary dissection of self-driven mechanisms of organogenesis and 3 The technology prototyping towards drug discovery/transplant applications. Though these efforts, Takebe lab aims to contribute to human health by establishing new therapies especially for treating pediatric intractable disease.

513-803-7807 takanori.takebe@cchmc.org

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Takanori Takebe, MD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Associate Professor, Department of Regenerative Medicine, Yokohama City University, Japan

Phone 513-803-7807

Fax 513-636-5581

Email takanori.takebe@cchmc.org

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Visit the Takebe Lab and Visit the Takebe Lab at Cincinnati Children's Hospital Medical Center.

Clinical

Hepatology; transplantation

Research

Organoid; organogenesis; stem cell biology; transplantation; drug development

Biography

Dr. Takebe is an assistant professor at the Cincinnati Children’s Hospital Medical Center. His lab is developing and applying mini-organ technologies from human stem cells – namely organ bud transplants – in patients with a rare congenital metabolic disorder, ultimately expanding the clinical applications to diseases like liver cirrhosis. Also, he holds a joint appointment at the Department of Regenerative Medicine, Yokohama City University in Japan, where he directs a translational program of human induced pluripotent stem cell (iPSC) based liver bud based approach for congenital liver disorders by developing a cGMP manufacturing platform.

Dr. Takebe successfully administered more than six nationally funded projects, awarded number of prestigious awards such as NYSCF robertson investigator award, and produced high impact peer-reviewed publications from each project. His recent associate professor appointment, at the age 26, was one of the youngest recorded in Japan.

MD: Yokohama City University, Japan, 2011.

Shinozawa T, Yoshikawa H-Y, Takebe T*. Reverse Engineering Organ Buds through Self-Driven Condensation and Organization. Developmental Biology. 2016 Jun 27. (*Correspondence)

Takahashi Y, Takebe T*, Taniguchi H*. Engineering pancreatic tissues from stem cells towards therapy. Regenerative Therapy. 2016(3):15-23. (*Joint corresponding authors)

Kagimoto S, Takebe T*, Kobayashi S, Yabuki Y, Hori A, Hirotomi K, Mikami T, Uemura T, Maegawa J, Taniguchi H. Autotransplantation of monkey ear perichondrium-derived progenitor cells for cartilage reconstruction. Cell transplantation. 2016;25(5):951-62. (*Joint corresponding authors)

Takebe T*, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, Matsuzaki T, Yamazaki T, Toyohara T, Osafune K, Nakauchi H, Yoshikawa H-Y, Taniguchi H. Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation. Cell Stem Cell. 2015 Apr;16(5):556-565. (*Corresponding author, Selected as Cover Work)

Selected as Cover Work
Selected as Best of Cell Stem Cell
Previewed in Cell Stem Cell
Featured in Nature Method

Rashid T, Takebe T, Nakauchi H. Novel strategies for liver therapy using stem cells. Gut. 2015;64:1-4.

Zhang RR, Koike H, Takebe T. The visualization of human organogenesis from stem cells by recapitulating multicellular interactions. In Hyper Bio Assembler for 3D Cellular Systems. 2015:275-283.

Takebe T *, Kobayashi S, Suzuki H, Mizuno M, Chang YM, Yoshizawa E, Kimura M, Hori A, Asano J, Maegawa J, Taniguchi H. Transient vascularization of transplanted human adult–derived progenitors promotes self-organizing cartilage. Journal of Clinical Investigation. 2014 Oct;124(10):4325-34. (*Corresponding author)

Takebe T*, Zhang RR, Koike H, Kimura M, Yoshizawa E, Enomura M, Sekine K, Taniguchi H*. Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature Protocols. 2014;9:396–409. (*Corresponding author)

Koike H, Ueno Y, Naito T, Shiina T, Ouchi R, Obana Y, Mori M, Sekine K, Takebe T, Zheng YW, Isono K, Koseki H, Taniguchi H. Ring1B Promotes Hepatic Stem/Progenitor Cell Expansion via Simultaneous Suppression of Cdkn1a and Cdkn2a. Hepatology. 2014 Jul;60(1):323-33.

Takebe T*, Sekine K, Enomura M, Koike H, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguch H*: Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013;499:481–484. (*Corresponding author)

Selected as Science Breakthrough of the Year
Selected as Word Top5 discovery, Discover Magazine
Featured in Nature, Nature Medicine, Cell Stem Cell, Gastroenterology, Hepatology, Cell Research
Featured in The Economist, New Scientist magazine, Newton, etc

Grants

Robertson Investigator Award. Principal Investigator. New-York Stem Cell Foundation. Jan 2017-Dec 2021.

In vitro human organ generation by reconstituting spatiotemporal control of multiple cellular interactions. Principal Investigator. PRESTO, JST. Oct 2013-Mar 2017.

Joshua S. Waxman, PhD

Joshua S. Waxman, PhD, uses genetic, molecular and cellular biological techniques to understand the underlying mechanisms of congenital heart defects and cardiomyocyte formation during development.
Visit the Waxman Lab.

513-636-7232 joshua.waxman@cchmc.org

Matthew T. Weirauch, PhD

Matthew T. Weirauch, PhD, is a computational biologist. His lab seeks to understand the mechanisms of gene transcriptional regulation. Current projects focus on characterizing transcription factor binding specificities, and developing methods for modeling their interactions with DNA, both in vitro and in vivo. His lab applies insights from basic research on transcription factor-DNA interactions to study the mechanisms underlying complex diseases.

Visit the Weirauch Lab.

513-803-9078 matthew.weirauch@cchmc.org

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Matthew T. Weirauch, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-9078

Email matthew.weirauch@cchmc.org

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Transcription factors; transcriptional regulation; functional genomics; genome analysis

Visit the Weirauch Lab.

Biography

Dr. Weirauch is a computational biologist. His lab seeks to understand the mechanisms of gene transcriptional regulation. Current projects focus on characterizing transcription factor binding specificities, and developing methods for modeling their interactions with DNA, both in vitro and in vivo. His lab applies insights from basic research on transcription factor-DNA interactions to study the mechanisms underlying complex diseases.

Postdoctoral Fellow: University of Toronto (Donnelly Center for Cellular and Biomolecular Research), Toronto, Ontario, Canada.

PhD: Bioinformatics, University of California Santa Cruz, Santa Cruz, California.

BSc: Computer Science, Pennsylvania State University, University Park, PA.

Alipanahi B, Delong A, Weirauch MT, Frey BJ. Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning. Nat Biotechnol. 2015 Aug;33(8):831-8.

Narasimhan K, Lambert SA, Yang AW, Riddell J, Mnaimneh S, Zheng H, Albu M, Najafabadi HS, Reece-Hoyes JS, Fuxman Bass JI, Walhout AJ, Weirauch MT, Hughes TR. Mapping and analysis of Caenorhabditis elegans transcription factor sequence specificities. Elife. 2015 Apr 23;4.

Weirauch M, Yang A, Albu M, Cote A, Montenegro-Montero A, Drewe P, Najafabadi H, Lambert S, Mann I, Cook K, Zheng H, Goity A, van Bakel H, Lozano J, Galli M, Lewsey M, Huang E, Mukherjee T, Chen X, Reece-Hoyes J, Govindarajan S, Shaulsky G, Walhout AJM, Bouget F, Ratsch G, Larrondo L, Ecker J, Hughes T. Determination and inference of eukaryotic transcription factor sequence specificity. Cell. 2014 Sep 11;158(6):1431-1443.

Ray D*, Kazan H*, Cook K*, Weirauch M*, Najafabadi H*, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat L, Dale R, Smith S, Yarosh C, Kelly S, Nabet B, Mecenas D, Li W, Laishram R, Qiao M, Lipshitz H, Piano F, Corbett A, Carstens R, Frey B, Anderson R, Lynch K, Penalva L, Lei E, Fraser A, Blencowe B, Morris Q, Hughes T. A compendium of RNA binding motifs for decoding gene regulation. Nature. 2013 Jul 10;499(7457):172-177. *co-first authors.

Weirauch M, Cote A, Norel R, Annala M, Zhao Y, Riley T, Saez-Rodriguez J, Cokelaer T, Vedenko A, Talukder S, DREAM5 Consortium, et al. Evaluation of methods for modeling transcription factor sequence specificity. Nature Biotechnology. 2013 Jan 27;31(2):126-34.

Grants

Viral transcription factor interactions with disease-associated genetic variants. Principal Investigator. Trustee Award, Cincinnati Children's. Jul 2014-Jun 2016.

Translational Genomics Analysis Core. Co-Investigator. NIH/NCRR CCTST T1 Pilot, Cincinnati Children's. Jul 2014-Jun 2016.

Decoding C2H2 Zinc Fingers. Collaborator. Canadian Institutes of Health Research (CIHR) Operating Grant. Oct 2013-Sep 2016.

James M. Wells, PhD Director for Research, Division of Endocrinology

Jim Wells, PhD, is focused on development of gastrointestinal and endocrine organs and how they maintain systemic metabolic homeostasis postnatally. Researchers in the Wells lab have also pioneered approaches to differentiate human pluripotent stem cells into gastrointestinal (GI) tissue organoids of the stomach, intestine, and colon. Organoids are being used to study endocrine control of metabolism, congenital defects of the digestive tract, and genetic forms of diabetes that affect patients in the center. Moreover, Dr. Wells and colleagues are using organoids as a basis for tissue engineering efforts to generate functional tissues for transplantation.
Visit the Wells Lab or learn more about CuSTOM.

513-636-8767 james.wells@cchmc.org

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James M. Wells, PhD

Director for Research, Division of Endocrinology

Chief Scientific Office, Center for Stem Cell and Organoid Medicine (CuSTOM)

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8767

Fax 513-636-4317

Email james.wells@cchmc.org

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Research

Understanding the development of the pancreas, and gastrointestinal organs; generating 3-dimensional human tissues from pluripotent stem cells and using these as human models of diabetes and digestive disease.

For more information, please visit the Wells lab web page or visit the CuSTOM web page.

Biography

The focus of his teams basic research has been to identify the molecular mechanisms involved in the embryonic development of endocrine cells including pancreatic beta cells and tissues of the gastrointestinal tract. Their translational projects have focused on identifying new approaches to improve child health in several ways: 1. To identify and use embryonic pathways to generate complex, three-dimensional organ tissues from pluripotent stem cells, 2. Use these tissues to develop new in vitro human models for diabetes and digestive disease research and 3. Develop long-term, therapeutic strategies for cell and tissue-replacement therapies.

BS: Biochemistry, Molecular and Cell Biology, University of Maine, Orono, ME, 1987.

PhD: Graduate program in Genetics, SUNY at Stony Brook, New York, 1995.

Postdoctoral Fellow: Harvard University, Cambridge MA, 1996 - 2001.

View Dr. Wells PubMed Publications.

McCracken KW, Catá E, Crawford C, Sinagoga KL, Schumacher M, Mayhew CN, Zavros Y, Wells JM. Modelling human development and disease in pluripotent stem cell-derived gastric organoids. Nature. 2014 Dec 18;516(7531):400-4.

Watson CL, Mahe MM, Howell JC, Munera J, Sundaram N, Schweitzer J, Vallance JE, Shroyer NF, Wells JM, Helmrath MA. An in vivo model of human small intestine using pluripotent stem cells. Nat Med. 2014 Nov;20(11):1310-4.

Ji H, Zhang X, Oh S, Mayhew C, Ulm A, Somineni H, Ericksen M, Wells J, Khurana Hershey GK. Dynamic transcriptional and epigenomic reprogramming from pediatric nasal epithelial cells to induced pluripotent stem cells. J Allergy Clin Immunol. 2014 Oct 14, pii:S0091-6749(14)01262-7.

Chlon TM, Hoskins EE, Mayhew CN, Wikenheiser-Brokamp KA, Davies SM, Mehta P, Myers KC, Wells JM, Wells, SI. High-Risk Human Papillomavirus E6 Protein Promotes Reprogramming of Fanconi Anemia Patient Cells through Repression of p53 but Does Not Allow for Sustained Growth of Induced Pluripotent Stem Cells. J Virol. 2014 Oct 1;88(19)11315-26.

Jonatan D, Spence JR, Method AM, Sinagoga K, Kofron M, Haataja L, Arvan P, Deutsch GH, Wells JM. Sox17 regulates insulin secretion in the normal and pathologic beta cell. PLoS One. 2014 Aug 21;9(8):e104675.

Schiesser JV, Wells JM. Generation of beta cells from human pluripotent stem cells: are we there yet? Ann N Y Acad Sci. 2014 Apr;1311:124-37.

Runck LA, Method A, Bischoff A, Levitt M, Peña A, Collins MH, Gupta A, Shanmukhappa S, Wells JM, Guasch G. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human. Dis Model Mech. 2014 Apr;7(4):483-93.

Wells JM, Spence JR. How to make an intestine. Development. 2014 Feb;141(4):752-60.

Delgiorno KE, Hall JC, Takeuchi KK, Pan FC, Halbrook CJ, Washington MK, Olive KP, Spence JR, Sipos B, Wright CV, Wells JM, Crawford HC. Identification and manipulation of biliary metaplasia in pancreatic tumors. Gastroenterology. 2014 Jan;146(1):233-44.e5.

Suissa Y, Magenheim J, Stolovich-Rain M, Hija A, Collombat P, Mansouri A, Sussel L, Sosa-Pineda B, McCracken K, Wells JM, Heller RS, Dor Y, Glaser B. Gastrin: a distinct fate of neurogenin3 positive progenitor cells in the embryonic pancreas. PLoS One. 2013 Aug 5;8(8):e70397.

Grants

Investigation of regional identity in human intestinal stem cells. Principal investigator (along with Shroyer NF, PI and Helmrath M, PI). National Institutes of Health. Sep 2014 – Aug 2019. NIH U01DK103117.

Single Cell Dissection of Human Intestine Development. Principal Investigator. National Institutes of Health. Sep 2013 – Aug 2018. NIH 1R01DK098350.

Control of human endocrine cell development. Contact Principal Investigator. National Institutes of Health. Apr 2012 – Mar 2017. NIH 1R01DK092456-01.

Transcriptional Control of Placental Differentiation. Co-Investigator. National Institutes of Health. Feb 2011 – Jan 2016. NIH R01 HD065339.

Jeffrey A. Whitsett, MD Co-Director, Perinatal Institute

Jeffrey A. Whitsett, MD, is internationally known for his research in pulmonary medicine, as well as for his clinical expertise in neonatology. Dr. Whitsett has made a series for groundbreaking contributions to pulmonary medicine. His major pioneering work has been on surfactant proteins A, B, C, and D, cloning their genes, and clarifying their roles in lung development.
Visit the Whitsett Lab.

513-803-2790 jeffrey.whitsett@cchmc.org

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Jeffrey A. Whitsett, MD

Co-Director, Perinatal Institute

Chief, Section of Neonatology, Perinatal and Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-2790

Fax 513-636-7868

Email jeffrey.whitsett@cchmc.org

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Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy

Visit the Whitsett Lab.

Biography

Dr. Whitsett's laboratory discovered surfactant proteins B and C, cloned the genes encoding the surfactant proteins A, B, C, and D, Scgb1a1, TTF-1 and others and utilized transgenic mouse models to delete and mutate these genes in transgenic mice. They identified transcriptional networks regulating lung morphogenesis and perinatal lung maturation contributing to the understanding of the roles of TTF-1, CEBPα, SOX2, SOX17, FOXA1, FOXA2, FOXA3, SPDEF, KLF5, CDC42 and others using both in vitro and in vivo methods. They identified multiple transcription factors regulating goblet cell differentiation airway epithelial cells including critical role of SPDEF, FOXA3 and airway goblet cells controlling innate immunity. They produced transgenic mouse models for conditional deletion and expression of genes involved in lung development, disease, and repair. They have generated transgenic models of pulmonary adenocarcinoma and explored the role of transcription factors mediating pulmonary adenocarcinoma in vivo and in vitro. They utilized RNA-Seq, microarray, Chip-Seq in the application of Nex-Gen sequencing and bioinformatics to identify and understand networks involved in the regulation of lung development and disease using clinical sample, as well as in vitro and in vivo models.

Dr. Whitsett has a long interest in training both in the clinical setting in “Neonatology” and in “Pulmonary Biology” and has contributed to the direct training of more than 80 graduate or post-graduate students in his laboratory. The scope of his work is represented in several recent reviews. Initial discoveries from his laboratory provided early insights into the genes and proteins critical for surfactant function including ABCA3, SFTPC, SFTPB, SFTPA, SFTPD.

MD: Columbia University, New York, NY, 1973.

Residency: Pediatrics, Mt. Sinai Hospital, New York City, 1974 to 1976.

Fellowship: Neonatology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 1976 to 1977.

Davies ER, Kelly JFC, Howarth PH, Wilson DI, Holgate ST, Davies DE, Whitsett JA, Haitchi HM. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life. JCI Insight. 2016;1:e87632.

Ustiyan V, Zhang Y, Perl A-KT, Whitsett JA, Kalin TV, Kalinichenko VV. ß-Catenin and Kras/Foxm1 Signaling Pathway are Critical to Restrict Sox9 in Basal Cells During Pulmonary Branching Morphogenesis. Dev Dyn. 2016;245:590-604.

Guo M, Wang H, Potter SS, Whitsett JA, Xu Y. SINCERA: A pipeline for single-cell RNA-Seq profiling analysis. PLoS Comput Biol. 2015;11:e1004575.

Kamath-Rayne BD, Du Y, Hughes M, Wagner EA, Muglia LJ, DeFranco EA, Whitsett JA, Salomonis N, Xu Y. Systems biology evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity. BMC Med Genomics. 2015;8:67.

Du Y, Guo M, Whitsett JA, Xu Y. ‘LungGENS’: a web-based tool for mapping single-cell gene expression in the developing lung. Thorax. 2015;70:1092-1094.

Snowball J, Ambalavanan M, Whitsett J, Sinner D. Endodermal Wnt signaling is required for tracheal cartilage formation. Dev Biol. 2015;405:56-70.

Wakata K, Tsuchiya T, Tomoshige K, Takagi K, Yamasaki N, Matsumoto K, Miyazaki T, Nanashima A, Whitsett JA, Maeda Y, Nagayasu T. A favorable prognostic marker for EGFR mutant non-small cell lung cancer: immunohistochemical analysis of MUC5B. BMJ Open. 2015;5:e008366.

Ishida N, Fukazawa T, Maeda Y, Yamatsuji T, Kato K, Matsumoto K, Shimo T, Takigawa N, Whitsett JA, Naomoto Y. A novel P13K inhibitor iMDK suppresses non-small cell lung Cancer cooperatively with a MEK inhibitor. Exp Cell Res. 2015;335:197-206.

Rajavelu P, Chen G, Xu Y, Kitzmiller JA, Korfhagen TR, Whitsett JA. Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation. J Clin Invest. 2015;125:2021-2031.

Snowball J, Ambalavanan M, Cornett B, Lang R, Whitsett J, Sinner D. Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall. Dev Biol. 2015;401:264-275.

Grants

Airway Progenitor Cell Proliferation and Differentiation During Lung Repair. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Jan 2012-Dec 2016. U01HL110964.

Transcriptional Programming of Asthma Related Pathology in Respiratory Epithelia. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Apr 2013-Mar 2018. 2 R01HL095580.

Omics of Lung Diseases. Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Sep 2013-May 2018. K12 HL119686.

“Lung Map” Atlas Research Center. Multiple Principal Investigators. National Institutes Health/National Heart, Lung, and Blood Institute. Jun 2014-Apr 2019. U01 HL122642.

Editing Alveolar Progenitor Cells for Correction of Monogenic Disease. Program Director/Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Sep 2016-Aug 2023. U01 HL134745.

Role of EMC3/TMEM111 in Alveolar Epithelial Cell Function. Program Director/Principal Investigator. National Institutes Health/National Heart, Lung, and Blood Institute. Apr 2017-Mar 2022. R01 HL136722.

Chunyue Yin, PhD

Chunyue Yin, PhD, studies the cellular and molecular basis of liver development and disease pathogenesis. She focuses on hepatic stellate cells, the key cell type responsible for hepatic fibrogenesis. She utilizes the zebrafish model to investigate the regulation of hepatic stellate cells during liver development and alcoholic liver injury, and their function in liver regeneration. Research in congenital biliary diseases is a second lab focus.

Visit the Yin Lab.

513-803-8096 chunyue.yin@cchmc.org

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Chunyue Yin, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-8096

Email chunyue.yin@cchmc.org

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Liver development; hepatic fibrosis and cirrhosis; hepatic stellate cells; stem cells and regeneration; congenital biliary diseases; zebrafish genetics

Visit the Yin Lab.

Biography

Dr. Yin conducted her doctoral research in Dr. Lilianna Solnica-Krezel’s laboratory at Vanderbilt University, where she investigated the molecular regulation of cell movements during zebrafish gastrulation and revealed the impact of gastrulation movements on somite development. In parallel, she participated in a forward genetic screen to identify novel regulators of zebrafish early development. She identified the calamity mutant that exhibits defects in notochord formation and pigmentation. Subsequent positional cloning revealed that a mutation in the atp7a gene, the zebrafish homolog of the human Menkes disease gene, was responsible for the calamity mutant phenotypes.

With a strong interest in building zebrafish models for human diseases, she decided to conduct her postdoctoral research in Dr. Didier Stainier’s laboratory, which is at the forefront of zebrafish digestive organ research. She received a postdoctoral fellowship from the Juvenile Diabetes Research Foundation to study pancreas development in zebrafish hands-off/han mutants that carry a mutation in the transcription factor gene hand2. Her research led to the discovery that the defective pancreatic development in han mutants is due to a failure in asymmetric gut looping. She also showed that gut-looping morphogenesis is dependent on extracellular matrix remodeling and revealed novel roles for Hand2 in this process. This work was published in Developmental Cell in 2010. Her work is now focused on the hepatic stellate cells and hepatic biliary cells. She has developed transgenic lines that mark these cell types and will use them and related reagents to characterize the cellular behaviors of these cells in liver development and disease, as well as the underlying molecular regulations.

BS: Evolution and Ecology, Fudan University, Shanghai, China, 2001.

PhD: Developmental Biology, Vanderbilt University, Nashville, TN, 2007.

Postdoctoral fellow: Developmental Biology, University of California at San Francisco, San Francisco, CA, 2012.

View PubMed publications

Delous M*, Yin C*, Shin D, Ninov N, Carten JD, Pan L, Ma TP, Farber SA, Moens CB, Stainier DYR. Sox9b is a key regulator of pancreaticobiliary ductal system development. PLoS Genetics. 2012. * These authors contribute equally to this work.

Yin C*, Evason K, Maher JJ, Stainier DYR. The bHLH transcription factor Hand2 marks hepatic stellate cells in zebrafish: analyses of stellate cell entry into the developing liver. Hepatology. 2012. * Co-corresponding author.

Yin C, Kikuchi K, Hochgreb T, Poss KD, Stainier DYR. Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish. Developmental Cell. 2010;18: 973-984.

Yin C, Kiskowski M, Pouille PA, Farge E, Solnica-Krezel L. Cooperation of polarized cell intercalations drives convergence and extension of presomitic mesoderm during zebrafish gastrulation. J Cell Biol. 2008;180: 221-232.

Yin C, Solnica-Krezel L. Convergence and extension movements affect dynamic notochord-somite interactions essential for zebrafish slow muscle morphogenesis. Dev Dyn. 2007;236: 2742-2756.

Yin C, Solnica-Krezel L. Convergence and extension movements mediate the specification and fate maintenance of zebrafish slow muscle precursors. Dev Biol. 2007;304(1): 141-155.

Mendelsohn B*, Yin C*, Wilm T, Johnson S, Solnica-Krezel L, Gitlin J. Atp7a determines a hierarchy of copper metabolism during embryogenesis essential for notochord development. Cell Metabolism. 2006;4(2):155-62. * These authors contributed equally to this work.

Lin F, Sepich DS, Chen S, Topczewski J, Yin C, Solnica-Krezel L, Hamm H. Essential roles of Gα12/13 signaling in distinct cell behaviors driving zebrafish convergence and extension gastrulation movements. J Cell Biol. 2005;169(5): 777-787.

Marlow F, Gonzalez EM, Yin C, Rojo C, Solnica-Krezel L. No tail co-operates with non-canonical Wnt signaling to regulate posterior body morphogenesis in zebrafish. Development. 2004;131(1): 203-216.

Yin C, Qian J, Fu C, Ma Y, Zheng S, Mao Y. Genetic diversity in natural populations of glycine tabacina in Fujian, China. J Gen Mol Biol. 2002;13: 6-12.

Yutaka Yoshida, PhD

Yutaka Yoshida, PhD, investigates the molecular mechanisms of neural circuit formation in the developing spinal cord, using many techniques including molecular biology, mouse genetics, biochemistry, and electrophysiology.
Visit the Yoshida Lab.

513-803-0943 yutaka.yoshida@cchmc.org

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Yutaka Yoshida, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-0943

Email yutaka.yoshida@cchmc.org

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Molecular mechanisms of neural circuit formation in the developing spinal cord.

Visit the Yoshida Lab.

BS: Keio University, 1994.

PhD: University of Tokyo, 1999.

Postdoctoral fellow: University of Tokyo, 1999-2002; Columbia University, 2002-2007.

Fukuhara K, Imai F, Ladle DR, Katayama K, Leslie JR, Arber S, Jessell TM, Yoshida Y. Specificity of monosynaptic sensory connections imposed by repellent sema3e-plexinD1 signaling. Cell Rep. 2013 Nov 14;5(3):748-58.

Katayama K, Imai F, Campbell K, Lang RA, Zhneg Y, Yoshida Y. RhoA and Cdc42 are required in pre-migratory progenitors of the medial ganglionic eminence ventricular zone for proper cortical interneuron migration. Development. 2013 Aug;140(15):3139-45.

Katayama K, Leslie JR, Lang RA, Zheng Y, Yoshida Y. Left-right locomotor circuitry depends upon RhoA-driven organization of the neuroepithelium in the developing spinal cord. Journal of Neuroscience. 2012 Jul 25;32(30):10396-407.

Leslie JR, Imai F, Fukuhara K, Takegahara N, Rizvi TA, Friedel RH, Wang F, Kumanogoh A, Yoshida Y. Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of changing semaphorin6D signaling inhibit synapse formation. Development. 2011.

Katayama K, Melendez J, Baumann JM, Leslie JR, Chauhan BK, Nemkul N, Lang RA, Kuan CY, Zheng Y, Yoshida Y. Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7607-12.

Pecho-Vrieseling E, Sigrist M, Yoshida Y, Jessell TM, and Arber S. Specificity of Monosynaptic Sensory-Motor Connections Encoded by Sema3e-PlexinD1. Nature. 2009 459:842-6.

Yoshida Y, Han B, Mendelsohn M, Jessell TM. PlexinA1 signaling directs the segregation of proprioceptive sensory axons in the developing spinal cord. Neuron. 2006 52:775-88.

Gu C*, Yoshida Y*, Livet J., Reimert DV, Mann F, Merte J, Henderson CE, Jessell TM, Kolodkin AL, Ginty DD. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science. 2005 307:265-8. (* denotes equal contribution)

Yoshida Y, Nakamura T, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, Miyasaka T, Yoshida EH, Umemori H, Kunisaki RK, Tani K, Ishii S, Mori S, Suganuma M, Noda T, Yamamoto T. Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes Dev. 2003 17:1201-6.

Yoshida Y, Tanakam S, Umemori H, Minowa O, Usui M, Ikematsu N, Hosoda E, Imamura T, Kuno J, Yamashita T, Miyazono K, Noda M, Noda T, Yamamoto T. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell. 2000 103:1085-97.

Amanda L. Zacharias, PhD

Amanda L. Zacharias, PhD, studies how gene expression is regulated by signaling pathways during embryonic development. The goal of her research is to understand how the combination of transcription factors and chromatin states unique to each cell are integrated by its genome to activate distinct targets via the same signaling pathway. Her laboratory uses the nematode, C. elegans, as a model system and measures gene expression in all embryonic cells using a quantitative time-lapse imaging approach.

513-636-2308 amanda.zacharias@cchmc.org

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Amanda L. Zacharias, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-2308

Email amanda.zacharias@cchmc.org

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Developmental gene regulation; transcriptional enhancers; Wnt signaling; Caenorhabditis elegans

Visit the Zacharias Lab.

BS: Biomedical Engineering, Northwestern University, Evanston, IL, 2003.

PhD: Cell & Developmental Biology, University of Michigan, Ann Arbor, MI, 2009.

Postdoctoral Fellow: University of Pennsylvania, Philadelphia, PA, 2011-2018.

Zacharias AL, Murray JI. Combinatorial decoding of the invariant C. elegans embryonic lineage in space and time. Genesis. 2016 Apr;54(4):182-97.

Burdick, JT, Walton T, Preston E, Zacharias AL, Raj A, Murray JI. Orthogonal cell population expression profiling identifies embryonic regulatory networks in C. elegans. BMC Genomics. 2016 Feb 29;17(1):159.

Zacharias AL, Walton T, Preston E, Murray JI. Quantitative Differences in Nuclear β-catenin and TCF pattern embryonic cells in C. elegans. PLOS Genetics. 2015 Oct 21;11(10).

Walton T, Preston E, Nair G, Zacharias AL, Raj A, Murray JI. The bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate in C. elegans embryonic progenitor cells to regulate robust development. PLOS Genetics. 2015 Mar 4;11(3).

Gage PJ, Kuang C, Zacharias AL. The homeodomain transcription factor PITX2 is required for specifying correct cell fates and establishing angiogenic privilege in the developing cornea. Dev Dyn. 2014 Nov;243(11):1391-400.

Richards JL, Zacharias AL, Walton T, Burdick JT, Murray JI. A quantitative model of normal C. elegans embryogenesis and its disruption after stress. Dev Biol. 2013 Feb 1;374(1):12-23.

Zacharias AL, Lewandoski M, Rudnicki MA, Gage PJ. Pitx2 is an upstream activator of extraocular myogenesis and survival. Dev Biol. 2011 Jan 15;349(2):395-405.

Zacharias AL, Gage PJ. Canonical Wnt/β-catenin signaling is required for maintenance but not activation of Pitx2 expression in the neural crest during eye development. Dev Dyn. 2010 Dec;239(12):3215-25.

Gage PJ, Zacharias AL. Signaling “cross-talk” is integrated by transcription factors in the development of the anterior segment of the eye. Dev Dyn. 2009 Jul 21;238(9):2149-2162.

Evans AL, Gage PJ. Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development. Hum Mol Genet. 2005 Nov 15;14(22):3347-59.

Grants

Mechanisms governing context-dependent Wnt activity in C. elegans embryogenesis. Principal Investigator. National Institute of General Medical Sciences. June 2018-June 2020. R00.

Aaron M. Zorn, PhD Perinatal Institute Endowed Research Chair

The Zorn lab investigates the cell signaling programs that control embryonic development of the digestive and respiratory system using a combination of animal models, human pluripotent stem cell-derived organoids and cutting-edge genomics. Current studies focus on the mechanisms of Wnt signaling in endoderm development and on elucidating the origins of trachea-esophageal birth defects.
Visit the Zorn Lab or learn more about CuSTOM.

513-636-3770 aaron.zorn@cchmc.org

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Aaron M. Zorn, PhD

Perinatal Institute Endowed Research Chair

Director, Center for Stem Cell and Organoid Medicine (CuSTOM)
Associate Director, Division of Developmental Biology
Associate Director, Digestive Health Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3770

Fax 513-636-4317

Email aaron.zorn@cchmc.org

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Development of lung, liver, pancreas and gastrointestinal tract; vertebrate embryology

Visit the Zorn Lab or learn more about CuSTOM.

Biography

Aaron M. Zorn, PhD, leads the Zorn lab with the research goal to understand the embryonic development respiratory and digestive systems. We use a combination of animal models and human pluripotent stem cells to investigate the genetic pathways underlying organ formation. The research in this lab helps our understanding of congenital diseases and the ability to generate organoids - human organ tissue in a dish, for regenerative medicine.

BSc: University of Toronto, Canada.

PhD: University of Texas, Austin, Texas, 1995.

Postdoctoral: Wellcome Trust Cancer Research Campaign Institute, University of Cambridge, Cambridge, England, 1996-1999.

Research Fellow: Wellcome Trust Gurdon Institute, Universtiy of Cambridge, Cambridge, England, 1999-2002.

Nolan K, Kattamuri C, Luedeke D, Deng A, Jagpal A, Zhang F, Linhardt R, Kenny AP, Zorn AM, Thompson TB. Structure of Protein Related to DAN and Cerberus (PRDC): Insights into the Mechanism of BMP Antagonism. Structure. 2013 Aug 6;21(8):1417-29.

Zhang Z, Rankin, SA, Zorn AM. Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endodermal progenitor cells. Dev Bio. 2013 Jun 1;378(1):1-12.

Bowes JB, Snyder KA, James-Zorn C, Ponferrada VG, Jarabek CJ, Burns KA, Bhattacharyya B, Zorn AM, Vize PD. The Xenbase literature curation process. Database (Oxford).2013 Jan 9;2013:bas046.

James-Zorn C, Ponferrada VG, Jarabek CJ, Burns KA, Segerdell EJ, Lee J, Snyder K, Bhattacharyya B, Karpinka JB, Fortriede J, Bowes JB, Zorn AM, Vize PD. Xenbase: expansion and updates of the Xenopus model organism database. Nucleic Acids Res. . 2013 Jan;41:D865-70.

Kattamuri C, Luedeke DM, Nolan K, Rankin SA, Greis KD, Zorn AM, Thompson TB. Members of the DAN Family are BMP Antagonists that form Highly Stable Noncovalent Dimers. J Mol Biol. 2012 Dec 14;424(5):313-27.

Shifley ET, Kenny AP, Rankin SA, Zorn AM. Prolonged FGF signaling is necessary for lung and liver induction in Xenopus. BMC Dev Bio. 2012 Sep 18;12:27.

Kenny AP, Rankin SA, Allbee AW, Prewitt AR, Zhang Z, Shifley E, Louza M, Zorn AM. Sizzled-Tolloid interactions maintain foregut progenitors by regulating Fibronectin-dependent BMP signaling. Dev Cell. 2012 Aug 14;23(2):292-304.

Rankin SA, Neto A, Gallas A, Gómez-Skarmeta JL, Zorn AM. Suppression of Bmp4 signaling by the zinc-finger repressors Osr1 and Osr2 is required for Wnt/beta-catenin-mediated lung specification in Xenopus. Development. 2012 Aug;139:3010-20.

Ponferrada VG, Fan J, Vallance JE, Hu S, Mamedova A, Rankin SA, Kofron M, Zorn AM, Hegde RS, Lang RA. CRIM1 Complexes with ß-catenin and Cadherins, Stabilizes Cell-Cell Junctions and Is Critical for Neural Morphogenesis. PLoS One. 2012;7(3):e32635.

Rankin SA, Zorn AM, Buchholz RD. New doxycycline-inducible transgenic lines in Xenopus. Dev Dyn. 2011 June;240(6):1467-74.

Rankin SA, Kormish J, Jegga, A Kofron M, Zorn AM. A gene regulatory network controlling hhex transcription in the anterior endoderm of the organizer. Dev Bio. 2011 Mar 15;351(2):297-310.

Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 2011. Feb 3;470:105-9.

Grants