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Bruce J. Aronow, PhD Co-director, Computational Medicine Center
Co-director, Computational Medicine Center
Professor, UC Department of Pediatrics
Dr. Aronow works toward unraveling both the role and mechanism by which the functional capabilities of the human genome shape human health and our ability to adapt to stressful challenges. The Aronow lab focuses on collaborative research projects and the development of informatics systems that leverage multiple disciplines of knowledge, expertise and diverse data. The goal is to improve our collective ability to formulate high-impact inferences, hypotheses and next-stage experiments that could have the highest overall impact for biomedical research. The lab’s current research focus is to find or support efforts to solve problems relevant to genomic medicine by developing, both independently and collaboratively, new algorithms, tools and methodologies in translational bioinformatics.
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.
Hawrylycz M, Miller JA, Menon V, Feng D, Dolbeare T, Guillozet-Bongaarts AL, Jegga AG, Aronow BJ, Lee CK, Bernard A, Glasser MF, Dierker DL, Menche J, Szafer A, Collman F, Grange P, Berman KA, Mihalas S, Yao Z, Stewart L, Barabási AL, Schulkin J, Phillips J, Ng L, Dang C, Haynor DR, Jones A, Van Essen DC, Koch C, Lein E. Canonical genetic signatures of the adult human brain. Nat Neurosci. 2015 Dec;18(12):1832-44.
Adams AK, Bolanos LC, Dexheimer PJ, Karns RA, Aronow BJ, Komurov K, Jegga AG, Casper KA, Patil YJ, Wilson KM, Starczynowski DT, Wells SI. IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival. Oncotarget. 2015 Oct 26.Unruh D, Srinivasan R, Benson T, Haigh S, Coyle D, Batra N, Keil R, Sturm R, Blanco V, Palascak M, Franco RS, Tong W, Chatterjee T, Hui DY, Davidson WS, Aronow BJ, Kalfa T, Manka D, Peairs A, Blomkalns A, Fulton DJ, Brittain JE,Weintraub NL, Bogdanov VY. Red Blood Cell Dysfunction Induced by High-Fat Diet: Potential Implications for Obesity-Related Atherosclerosis. Circulation. 2015 Nov 17;132(20):1898-908.
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. Dev Cell. 2015 Oct 12;35(1):49-62.
Pfluger PT, Kabra DG, Aichler M, Schriever SC, Pfuhlmann K, García VC, Lehti M, Weber J, Kutschke M, Rozman J, Elrod JW, Hevener AL, Feuchtinger A, Hrabě de Angelis M, Walch A, Rollmann SM, Aronow BJ, Müller TD, Perez-Tilve D, Jastroch M, De Luca M, Molkentin JD, Tschöp MH. Calcineurin Links Mitochondrial Elongation with Energy Metabolism. Cell Metab. 2015 Nov 3;22(5):838-50.
Mrug M, Zhou J, Yang C, Aronow BJ, Cui X, Schoeb TR, Siegal GP, Yoder BK, Guay-Woodford LM. Genetic and Informatic Analyses Implicate Kif12 as a Candidate Gene within the Mpkd2 Locus That Modulates Renal Cystic Disease Severity in the Cys1cpk Mouse. PLoS One. 2015 Aug 21;10(8):e0135678.
Nayak RC, Trump LR, Aronow BJ, Myers K, Mehta P, Kalfa T, Wellendorf AM, Valencia CA, Paddison PJ, Horwitz MS, Grimes HL, Lutzko C, Cancelas JA. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotentstem cells. J Clin Invest. 2015 Aug 3;125(8):3103-16.
Matrka MC, Hennigan RF, Kappes F, DeLay ML, Lambert PF, Aronow BJ, Wells SI. DEK over-expression promotes mitotic defects and micronucleus formation. Cel Cycle. 2015 May 6:1-15.
Sayed N, Wong WT, Ospino F, Meng S, Lee J, Jha A, Dexheimer P, Aronow BJ, Cooke JP. Transdifferentiation of human fibroblasts to endothelial cells: role of innate immunity. Circulation. 2015 Jan 20;131(3):300-9.
Chang KH, Sengupta A, Nayak RC, Duran A, Lee SJ, Pratt RG, Wellendorf AM, Hill SE, Watkins M, Gonzalez-Nieto D, Aronow BJ, Starczynowski DT, Civitelli R, Diaz-Meco MT, Moscat J, Cancelas JA. p62 is required for stem cell/progenitor retention through inhibition of IKK/NF-κB/Ccl4 signaling at the bone marrow macrophage-osteoblast niche. Cell Rep. 2014 Dec 24;9(6):2084-97.
Samantha A. Brugmann, PhD Member, Division of Plastic Surgery
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.
Visit the Brugmann Lab.
Member, Division of Plastic Surgery
Assistant Professor, UC Department of Surgery
Samantha A. Brugmann, PhD, is an assistant 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.
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
studies the molecular genetic control of mouse forebrain development with a particular focus on the generation of neuronal diversity in the ventral telencephalon.
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.
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.
Assistant Professor, UC Department of Pediatrics
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.
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.
Vaughn G. Cleghon, PhD
Associate Professor, UC Department of Pediatrics
Protein kinases in development and human disease
Visit the Cleghon Lab.
PhD: Waksman Institute of Microbiology, Rutgers, Piscataway, NJ, 1991.
Postdoctoral Fellow: Dr. Deborah Morrison ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research Center, Frederick, MD.
Group Leader: Beatson Institute for Cancer Research, Beatson Laboratories, UK.
Kinstrie R, Luebbering N, Miranda-Saavedra D, Sibbet G, Han J, Lochhead PA, Cleghon V. Characterization of a domain that transiently converts class 2 DYRKs into intramolecular tyrosine kinases. Sci Signal. 2010 Mar 2;3(111):ra16. Day JP, Cleghon V, Houslay MD, Davies SA. Regulation of a Drosophila melanogaster cGMP-specific phosphodiesterase by prenylation and interaction with a prenyl-binding protein. Biochem J. 2008 Sep 15;414(3):363-74. Lochhead PA, Kinstrie R, Sibbet G, Rawjee T, Morrice N, Cleghon V. A chaperone-dependent GSK3beta transitional intermediate mediates activation-loop autophosphorylation. Mol Cell. 2006 Nov 17;24(4):627-33.
Kinstrie R, Lochhead PA, Sibbet G, Morrice N, Cleghon V. dDYRK2 and Minibrain interact with the chromatin remodeling factors SNR1 and TRX. Biochem J. 2006;398:45-54.
Lochhead PA, Sibbet G, Morrice N, Cleghon V. Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell. 2005;121:925-36.
Roger Cornwall, MD Clinical Director, Pediatric Orthopaedic Surgery
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.
Visit the Cornwall Lab.
Clinical Director, Pediatric Orthopaedic Surgery
Surgical Director, Epidermolysis Bullosa Center
Director, Hand and Upper Extremity Surgery Fellowship
Associate Professor, UC Department of Orthopedic Surgery
Brachial plexus birth palsy; pediatric hand and wrist trauma; congenital hand and upper extremity abnormalities; complex pediatric elbow trauma and deformities; gymnast wrist.
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.
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 Apr 3.
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.
Eismann EA, Lucky AW, Cornwall R. Hand function and quality of life in children with epidermolysis bullosa. Pediatr Dermatol. 2014 Mar-Apr;31(2):176-82.
Nikolaou S, Hu L, Tuttle LJ, Weekley H, Christopher W, Lieber RL, Cornwall R. Contribution of denervated muscle to contractures after neonatal brachial plexus injury: not just muscle fibrosis. Muscle Nerve. 2014 Mar;49(3):398-404.
Eismann EA, Bauer A, Kozin SH, Louden E, Cornwall R. The relationship between medical malpractice litigation and parent reports of patient function following neonatal brachial plexus palsy. J Bone Joint Surg Am. 2014 Mar 5;96(5):373-9.
Eismann EA, Little KJ, Kunkel ST, Cornwall R. Clinical research fails to support more aggressive management of pediatric upper extremity fractures. J Bone Joint Surg Am. 2013 Aug 7;95(15):1345-50.
Reading BD, Laor T, Salisbury SR, Lippert WC, Cornwall R. Quantification of humeral head deformity following neonatal brachial plexus palsy. J Bone Joint Surg Am. 2012 Sep 19;94(18):e136(1-8).
Weekley H, Nikolaou S, Hu L, Eismann E, Wylie C, Cornwall R. The effects of denervation, reinnervation, and muscle imbalance on functional muscle length and elbow flexion contracture following neonatal brachial plexus injury. J Orthop Res. 2012 Aug;30(8):1335-42.
Kunkel S, Eismann E, Cornwall R. Utility of the pediatric outcomes data collection instrument for assessing acute hand and wrist injuries in children. J Pediatr Orthop. 2011 Oct-Nov;31(7):767-72.
Nikolaou S, Peterson E, Kim A, Wylie C, Cornwall R. Impaired growth of denervated muscle contributes to contracture formation following neonatal brachial plexus injury. J Bone Joint Surg Am. 2011 Mar 2;93(5):461-70.
Steven A. Crone, PhD
Developmental biology; neurodegenerative disease; neural control of behavior; locomotion; respiration; motor circuits; amyotrophic lateral sclerosis (ALS; spinal muscular atrophy (SMA)
Visit the Crone Lab.
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
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.
Visit the De Falco Lab.
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.
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.
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;88(4):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.
DeFalco T, Capel B. Gonad morphogenesis in vertebrates: divergent means to a convergent end. Annu Rev Cell Dev Biol. 2009;25:457-82.
Nanda S*, DeFalco TJ*, Loh SH, Phochanukul N, Camara N, Van Doren M, Russell S. Sox100B, a Drosophila group E Sox-domain gene, is required for somatic testis differentiation. Sex Dev. 2009;3:26-37. (*co-first-authors)
DeFalco T, Camara N, Le Bras S, Van Doren M. Nonautonomous sex determination controls sexually dimorphic development of the Drosophila gonad. Dev Cell. 2008 Feb;14(2):275-86.
DeFalco T, Le Bras S, Van Doren M. Abdominal-B is essential for proper sexually dimorphic development of the Drosophila gonad. Mech Dev. 2004 Nov;121(11):1323-33.
DeFalco TJ, Verney G, Jenkins AB, McCaffery JM, Russell S, Van Doren M. Sex-specific apoptosis regulates sexual dimorphism in the Drosophila embryonic gonad. Dev Cell. 2003 Aug;5(2):205-16.
Prasad Devarajan, MD Director, Division of Nephrology and Hypertension
Director, Division of Nephrology and Hypertension
Medical Director, Stone Center
Director, Nephrology and Hypertension Clinical Laboratory
Louise M. Williams Endowed Chair
Clinical specialties: acute kidney injury, nephrotic syndrome, kidney stones
Visit the Devarajan Lab.
Premedical Studies: Bombay University, India, 1979.
MD: Bombay University, India, 1985.
Czech KA, Bennett M, Devarajan P. Distinct metalloproteinase excretion patterns in focal segmental glomerulosclerosis. Pediatr Nephrol. 2011 Jul 1.
Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P, Khandrika S, Mehta RL, Ambalavanan N. Baseline Values of Candidate Urine Acute Kidney Injury (AKI) Biomarkers Vary by Gestational Age in Premature Infants. Pediatr Res. 2011 Jun 3.
Abraham BP, Frazier EA, Morrow WR, Blaszak RT, Devarajan P, Mitsnefes M, Bryant JC, Sachdeva R. Cystatin C and neutrophil gelatinase-associated lipocalin as markers of renal function in pediatric heart transplant recipients. Pediatr Transplant. 2011 Apr 25.
Sundaram N, Bennett M, Wilhelm J, Kim MO, Atweh G, Devarajan P, Malik P. Biomarkers for early detection of sickle nephropathy. Am J Hematol. 2011 Jul;86(7):559-66.
Devarajan P, Krawczeski C. In reply to 'antifibrinolytic use during cardiac and hepatic surgery makes tubular proteinuria-based early biomarkers poor tools to diagnose perioperative acute kidney injury'. Am J Kidney Dis. 2011 Jun;57(6):960-1.
Piyaphanee N, Ma Q, Kremen O, Czech K, Greis K, Mitsnefes M, Devarajan P, Bennett MR. Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome. Proteomics Clin Appl. 2011 Jun;5(5-6):334-42.
Li S, Krawczeski CD, Zappitelli M, Devarajan P, Thiessen-Philbrook H, Coca SG, Kim RW, Parikh CR; for the TRIBE-AKI Consortium. Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: A prospective multicenter study. Crit Care Med. 2011 Jun;39(6):1493-1499.
Krawczeski CD, Woo JG, Wang Y, Bennett MR, Ma Q, Devarajan P. Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr. 2011 Jun;158(6):1009-1015.e1.
Basu RK, Devarajan P, Wong H, Wheeler DS. An update and review of acute kidney injury in pediatrics. Pediatr Crit Care Med. 2011 May;12(3):339-47.
Devarajan P. Biomarkers for the early detection of acute kidney injury. Curr Opin Pediatr. 2011 Apr;23(2):194-200.
SK Dey, PhD Lova Riekert Chair and Professor of Pediatrics, Cancer and Cell Biology
Lova Riekert Chair and Professor of Pediatrics, Cancer and Cell Biology
Director, Division of Reproductive Sciences
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
Visit the Dey Lab.
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
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
Pre-clinical validation of anti-angiogenic agents for use in the treatment of retinopathies, cancer and pulmonary disease.
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
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.
Hepatic development and regeneration; three-dimensional hepatic architecture; Notch signaling; hepatobiliary disease
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.
Chen TW, Broadus MR, Huppert SS, Lee E. Reconstitution Of β-catenin Degradation In Xenopus Egg Extract. J Vis Exp. 2014 Jun 17;(88).
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.
Hang BI, Thorne CA, Robbins DJ, Huppert SS, Lee LA, Lee E. Screening for small molecule inhibitors of embryonic pathways: sometimes you gotta crack a few eggs. Bioorg Med Chem. 2012 Mar 15;20(6):1869-77.
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.
Rulang Jiang, PhD Member, Division of Developmental Biology
is a developmental biologist directing research programs in craniofacial biology. His lab generates and uses mutant mouse models to investigate the genetic and developmental basis of craniofacial birth defects, including cleft lip, cleft palate, tooth defects, and other craniofacial deformities. His lab also studies development of joints, including long bone joints in the limb and the temporomandibular joint of the jaw.
Visit the Jiang Lab.
Member, Division of Developmental Biology
BS: Nanjing Normal University, Nanjing, China, 1984.
MS: Genetics, Chinese Academy of Sciences, Beijing, China, 1987.
PhD: Wesleyan University, Middletown, CT, 1995.
Gao Y, Lan Y, Liu H, Jiang R. The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation. Dev Biol. 2011 Apr;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;350(2):520-531.
Liu W, Watson SS, Lan Y, Keene DR, Ovitt CE, Liu H, Schweitzer R, Jiang R. The atypical homeodomain transcription factor Mohawk controls tendon morphogenesis. Mol Cell Biol. 2010 Oct;30(20):4797-4807.
Lan Y, Jiang R. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development. 2009 Apr;136(8):1387-1396.
Zhang Z, Lan Y, Chai Y, Jiang R. Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row. Science. 2009;323(5918):1232-1234.
Lan Y, Wang Q, Ovitt CE, Jiang R. A unique mouse strain expressing Cre recombinase for tissue-specific analysis of gene function in palate and kidney development. Genesis. 2007;45(10):618-624.
Jiang R, Bush JO, Lidral AC. Development of the upper lip: morphogenetic and molecular mechanisms. Dev Dyn. 2006;235(5):1152-1166.
Wang Q, Lan Y, Cho ES, Maltby KM, Jiang R. Odd-skipped related 1 (Odd1) is an essential regulator of heart and urogenital development. Dev Biol. 2005;288(2):582-594.
Lan Y, Ovitt CE, Cho ES, Maltby KM, Wang Q, Jiang R. Odd-skipped related 2 (Osr2) encodes a key intrinsic regulator of secondary palate growth and morphogenesis. Development. 2004;131(13):3207-3216.
Bush JO, Lan Y, Jiang R. The cleft lip and palate defects in the Dancer mutant mice result from gain of function of the Tbx10 gene. Proc Nat Acad Sci U S A. 2004;101(18):7022-7027.
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.
Visit the Kalinichenko Lab.
Lung development; cell proliferation; carcinogenesis; transcriptional regulation of gene expression.
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 Research Associate, Division of Developmental Biology
Research Associate, Division of Developmental Biology
Early vertebrate patterning; germ layer formation
Kofron M, Demel T, Xanthos J, Lohr J, Sun B, Sive H, Osada S, Wright C, Wylie C, Heasman J. Mesoderm induction in Xenopus is a zygotic event regulated by maternal VegT via TGFbeta growth factors. Development. 1999 126:5759-5770.
Heasman J, Kofron M, Wylie C. Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach. Developmental Biology. 2000; 222:124-134.
Xanthos JB, Kofron M, Wylie C, Heasman J. Maternal VegT is the initiator of a molecular network specifying endoderm in Xenopus laevis. Development. 2001; 128(2):167-180.
Raphael Kopan, PhD Director, Division of Developmental Biology
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.
Visit the Kopan Lab.
Director, Division of Developmental Biology
Notch signaling; kidney organogenesis; skin organogenesis; TSLP signaling in cancer
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
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.
Associate Professor, UC Department of Surgery
UC Department of Pediatrics
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
Director, Visual Systems Group
UC Department of Ophthalmology
Wnt ligands in tumorigenesis; vascular regression and tissue regeneration; lens induction and morphogenesis.
Visit the Lang Lab.
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
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.
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).
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.
Jun Ma, PhD
researches developmental processes at a quantitative and systems level. His team investigates fundamental mechanisms of development through a combination of quantitative experimental approaches and theoretical and simulation approaches.
Molecular mechanisms of gene regulation and embryonic development
BS: Peking University, 1978-1982.
PhD: Harvard University, Cambridge, MA, 1983-1988 (degree awarded 1990).
Wu H, Manu Jiao R, Ma J. Temporal and spatial dynamics of scaling-specific features of a gene regulatory network in Drosophila. Nat Commun. 2015.
Liu J, Ma J. Modulation of temporal dynamics of gene transcription by activator potency in the Drosophila embryo. Development. 2015;142:3781-3790.
Cheung D, Ma J. Probing the impact of temperature on molecular events in a developmental system. Sci Rep. 2015;5:13124.
He F, Wei C, Wu H, Cheung D, Jiao R, Ma J. Fundamental origins and limits for scaling a maternal morphogen gradient. Nat Commun. 2015;6:6679.
Cheung D, Miles C, Kreitman M, Ma J. Adaptation of the length scale and amplitude of the Bicoid gradient profile to achieve robust patterning in abnormally large Drosophila melanogaster embryos. Development. 2014;141(1):124-135.
Liu J, Ma J. Dampened regulates the activating potency of Bicoid and the embryonic patterning outcome in Drosophila. Nat Commun. 2013;4:2968.
He F, Ren J, Wang W, Ma J. Evaluating the Drosophila Bicoid morphogen gradient system through dissecting the noise in transcriptional bursts. Bioinformatics. 2012;28:970-975.
Liu J, Ma J. Fates-shifted is an F-box protein that targets Bicoid for degradation and regulates developmental fate determination in Drosophila embryos. Nat Cell Biol. 2011 Jan;13(1):22-9.
Cheung D, Miles C, Kreitman M, Ma J. Scaling of the Bicoid morphogen gradient by a volume-dependent production rate. Development. 2011;138:2741-2749.
Christopher N. Mayhew, PhD Co-Director, Pluripotent Stem Cell Facility
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.
Co-Director, Pluripotent Stem Cell Facility
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(7332):105-9.
Mayhew CN, Wells JM. Converting human pluripotent stem cells into beta-cells: recent advances and future challenges. Curr Opin Organ Transplant. 2010 Feb;15(1):54-60.
Masato Nakafuku, MD, PhD Ohio Eminent Scholar
Ohio Eminent Scholar
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
RNA-related inflammation in obesity and metabolic diseases
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.
Satoshi H. Namekawa, PhD
The long-term goal of Dr. Namekawa's research is to understand the mechanisms and evolution of epigenetic events during mammalian reproduction. One of the focus areas is epigenetic regulation of sex chromosomes in germ cell development. Recently, his laboratory demonstrated that DNA damage response pathways trigger epigenetic programming on the sex chromosomes in germ cells. An on-going direction of the laboratory is to pursue a general link between DNA damage response pathways and epigenetic programming. Another goal of the laboratory is to identify novel factors and related pathways that control epigenetic programming during mouse reproduction, especially focusing on the events occurring on sex chromosomes during spermatogenesis as well as the regulatory mechanisms in germline stem cells.
Visit the Namekawa Lab.
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, followed by his faculty appointment at Cincinnati Children's in 2009. He is funded by NIH R01 Award and the Basil O’Connor Award from March of Dimes Foundation.
He received the 2015 New Investigator Award from the Society for the Study of Reproduction.
PhD: Tokyo University of Science, Japan, 2005.
BS: Tokyo University of Science, Japan, 2000.
Sin HS, Kartashov AV, Hasegawa K,Barski A, Namekawa SH. Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline. BMC Biol. 2015 Jul 22;13:53.
Kato Y, Alavattam KG, Sin HS, Meetei A, Pang Q, Andreassen PR, Namekawa SH. FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis. Hum Mol Genet. 2015 Jun 29.
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.
Hu YC, Namekawa SH. Functional significance of the sex chromosomes during spermatogenesis. Reproduction. 2015 Jun;149(6):R265-R277.
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.
Broering TJ*, Alavattam KG*, Sadreyev RI, Ichijima Y, Kato Y, Hasegawa K, Camerini-Otero RD, Lee JT, Andreassen PR, Namekawa SH. BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis. (*equal contribution) J Cell Biol. 2014 Jun 9;205(5):663-75.
Namekawa SH. Slide preparation method to preserve three-dimensional chromatin architecture of testicular germ cells.J Vis Exp. 2014 Jan 10;(83).
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.
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.
Molecular biology; genetics.
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.
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.
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.
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.
Park JS, Valerius MT, McMahon AP. Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development. Development. 2007;134, 2533-2539.
Park JS, Roberts JW. Role of DNA bubble rewinding in enzymatic transcription termination. Proc Natl Acad Sci U S A. 2006;103, 4870-4875.
Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Developmental cell. 2005;9, 283-292.
Roberts J, Park, JS. Mfd, the bacterial transcription repair coupling factor: translocation, repair and termination. Current opinion in microbiology. 2004;7, 120-125.
Park JS, Marr MT, Roberts JW. E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation. Cell. 2002;109, 757-767.
S. Steven Potter, PhD
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.
Rolf W. Stottmann, PhD
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.
Stottmann RW, Turbe-Doan A, Tran P, Kratz L, Moran J, Kelley R, Beier DR. Cholesterol metabolism is required for intracellular hedgehog signal transduction in vivo. PLoS Genetics. 2011.
Stottmann RW, Moran J, Turbe-Doan A, Driver E, Kelly M, Beier DR. An ENU screen for neurodevelopmental mutations in the mouse. Genetics. 2011 Jul;188(3):615-24.
Stottmann RW, Klingensmith J. Bone morphogenetic protein signaling is required in the dorsal neural folds before neurulation for the induction of spinal neural crest cells and dorsal neurons. Dev Dyn. 2011 Apr;240(4):755-65.
Stottmann RW, Beier DR. Using ENU mutagenesis for phenotype-driven analysis of the mouse. Methods Enzymol. 2010;477:329-48.
Stottmann RW, Bjork BC, Doyle JB, Beier DR. Identification of a Van der Woude syndrome mutation in the cleft palate 1 mutant mouse. Genesis. 2010 May;48(5):303-8.
Stottmann RW, Tran PV, Turbe-Doan A, Beier DR. Ttc21b is required to restrict sonic hedgehog activity in the developing mouse forebrain. Dev Biol. 2009 Nov 1;335(1):166-78.
Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008 Apr;40(4):403-10.
Stottmann RW, Berrong M, Matta K, Choi M, Klingensmith J. The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms. Dev Biol. 2006 Jul 15;295(2):647-63.
Stottmann RW, Choi M, Mishina Y, Meyers EN, Klingensmith J. BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium. Development. 2004 May;131(9):2205-18.
Stottmann RW, Anderson RM, Klingensmith J. The BMP antagonists Chordin and Noggin have essential but redundant roles in mouse mandibular outgrowth. Dev Biol. 2001 Dec 15;240(2):457-73.
Saulius Sumanas, PhD
Molecular mechanisms of vasculogenesis and angiogenesis
Visit the Sumanas Lab.
BS: Vilnius University, Biochemistry, Vilnius, Lithuania, 1995.
PhD: University of Minnesota, Department of Biochemistry, Minneapolis / St. Paul, MN, 2000.
Postdoctoral Fellow: University of California, Los Angeles, CA, 2002-2007.
Glenn NO, McKane M, Kohli V, Wen KK, Rubenstein PA, Bartman T, Sumanas S. W-Loop of Alpha-Cardiac Actin is Critical for Heart Function and Endocardial Cushion Morphogenesis in Zebrafish. Mol Cell Biol. 2012 Sep;32(17):3527-40.
Wong KS, Rehn K, Palencia-Desai S, Kohli V, Hunter W, Uhl JD, Rost MS, Sumanas S. Hedgehog signaling is required for differentiation of endocardial progenitors in zebrafish. Dev Biol. 2012 Jan 15:361:377-91.
Palencia-Desai S, Kohli V, Kang J, Chi NC, Black BL, Sumanas S. Vascular endothelial and endocardial progenitors differentiate as cardiomyocytes in the absence of Etsrp/Etv2 function. Development. 2011 Nov;138(21):4721-32.
Proulx K, Wong KS, Balciunas D, Sumanas S.Zebrafish Enhancer Trap Line Recapitulates Embryonic aquaporin 1a Expression Pattern In Vascular Endothelial Cells. Int J Dev Biol. 2011;55(6):613-8.
Kohli V, Rehn K, Sumanas S. Single cell fate mapping in zebrafish. J Vis Exp. 2011 56, e3172.
Proulx K, Lu A, Sumanas S. Cranial vasculature in zebrafish forms by angioblast cluster-derived angiogenesis. Dev Biol. 2010 Dec 1;348(1):34-46.
Wong KS, Proulx K, Rost MS, Sumanas S. Identification of vasculature-specific genes by microarray analysis of Etsrp/Etv2 overexpressing zebrafish embryos. Dev Dyn. 2009 Jul;238(7):1836-50.
Sumanas S, Gomez G, Zhao Y, Park C, Choi K, Lin S. Interplay between Etsrp/ER71, scl and alk8 signaling controls endothelial and myeloid cell formation. Blood. May. 2008 111(9):4500-4510.
Sumanas S, Lin S. Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLOS Biol. 2006 Jan;4(1):e10.
Sumanas S, Jorniak T, Lin S. Identification of novel vascular endothelial-specific genes by the microarray analysis of the zebrafish cloche mutants. Blood. 2005 Jul;106(2):534-541.
Timothy W. Vogel, MD Faculty Neurosurgeon, Division of Pediatric Neurosurgery
Faculty Neurosurgeon, Division of Pediatric Neurosurgery
Assistant Professor, UC Department of Neurosurgery
Tim Vogel, MD, joined the Division of Pediatric Neurosurgery at Cincinnati Children’s in 2013 as an assistant professor of neurosurgery and developmental biology within the University of Cincinnati College of Medicine. Dr. Vogel is a graduate of Princeton University and Columbia University’s College of Physicians and Surgeons. Dr. Vogel completed his residency at the University of Iowa Hospitals and Clinics in 2011. He then completed a minimally invasive fellowship at Boston Children’s Hospital at Harvard University, followed by a pediatric neurosurgery fellowship at St. Louis Children’s Hospital at Washington University in St. Louis.
Dr. Vogel specializes in craniofacial surgery and the use of endoscopy in the minimally invasive treatment of children. He also utilizes endoscopy and his expertise with minimally invasive surgery to treat hydrocephalus and certain tumors of the brain.
In addition to his clinical activities, Dr. Vogel is a principal investigator in the Division of Developmental Biology focused on human and molecular genetics of hydrocephalus and other neurodevelopmental disorders. Dr. Vogel has completed postdoctoral fellowships for the Howard Hughes Medical Institute at the University of Iowa and at Massachusetts General Hospital. Dr. Vogel is focused on cilia (hair like structures in the brain) and their contribution to hydrocephalus during development. He utilizes basic and translational applications to study cellular signaling in hydrocephalus with the goal of developing innovative treatment strategies for this disease.
Dr. Vogel is a member of the American Association for the Advancement of Science, the American Association of Neurological Surgeons, the American Society of Craniofacial Surgery, the American Society of Human Genetics, the Ciliopathy Alliance, and the Congress of Neurological Society and the Society of Neuroscience.
MD: Columbia University College of Physicians and Surgeons, New York, NY, 2005.
Residency: University of Iowa Hospitals and Clinics, Iowa City, IA, 2011.
Research Fellowship: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2013.
Pediatric Neurosurgery Fellowship: St. Louis Children’s Hospital, Washington University in St. Louis, Division of Pediatric Neurosurgery, St. Louis, MO, 2013.
Minimally Invasive Fellowship: Boston Children’s Hospital, Harvard University, Department of Neurosurgery, Boston, MA, 2012.
Postdoctoral Research Fellowship: Harvard Medical School, Harvard University, Boston, MA, 2012.
Postdoctoral Research Fellowship: Howard Hughes Medical Institute, University of Iowa, Iowa City, IA, 2010.
Zhang Q, Nishimura DY, Vogel T, Shao J, Swiderski R, Yin T, Searby C, Carter CC, Kim G, Bugge K, Stone EM, Sheffield VC. BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking. J Cell Sci. 2013 Jun 1;126(Pt 11):3272-80.
Carter CS*, Vogel TW*, Zhang Q, Seo S, Swiderski RE, Moninger TO, Cassell MD, Thedens DR, Keppler-Noreuil KM, Nopoulos P, Nishimura DY, Searby CC, Bugge K, Sheffield VC. Abnormal development of NG2+PDGFR-α+ neural progenitor cells leads to neonatal hydrocephalus in a ciliopathy mouse model. Nat Med. 2012 Dec;18(12):1797-804. Cover Article. (*EQUAL AUTHOR CONTRIBUTION)
Vogel TW, Carter CS, Abode-Iyamah K, Zhang Q, Robinson S. The role of primary cilia in the pathophysiology of neural tube defects. Neurosurgery Focus. 2012 Oct; 33(4):E2. Cover Article.
Vogel TW, Manjila S, Cohen AR. Novel neurodevelopmental disorder in a case of a giant occipitoparietal meningoencephalocele. J Neurosurg Pediatr. 2012 Jun 8. Cover Article.
Zhang Q, Nishimura DY, Seo S, Vogel T, Morgan DA, Searby C, Bugge K, Stone EM, Rahmouni K, Sheffield VC. Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes. Proc Natl Acad Sci USA. 2011 Dec 20;108(51):20678-83.
Thompson S, Recober A, Vogel TW, Kuburas A, Sheffield VC, Russo AF, Stone EM. Light aversion in mice depends on nonimage-forming irradiance detection. Behav Neurosci. 2010 Dec; 124(6): 821-7.
Vogel TW, Vortmeyer AO, Lubensky IA, Lee YS, Furuta M, Ikejiri B, Kim HJ, Lonser RR, Oldfield EH, Zhuang Z. Coexpression of erythropoietin and its receptor in endolymphatic sac tumors. J Neurosurg. 2005 Aug;103(2):284-8.
Vogel TW, Zhuang Z, Li J, Okamoto H, Furuta M, Lee YS, Zeng W, Oldfield EH, Vortmeyer AO, Weil RJ. Proteins and protein pattern differences between glioma cell lines and glioblastoma multiforme. Clin Cancer Res. 2005 May 15;11(10):3624-32.
Vogel TW, Brouwers FM, Lubensky IA, Vortmeyer AO, Weil RJ, Walther MM, Oldfield EH, Linehan WM, Pacak K, Zhuang Z. Differential expression of erythropoietin and its receptor in von Hippel-Lindau-associated and MEN type 2-associated pheochromocytomas. J Clin Endocrinol Metab. 2005 June;90(6):3747-51.
Lee YS, Vortmeyer AO, Lubensky IA, Vogel TW, Ikejiri B, Ferlicot S, Benoit G, Giraud S, Oldfield EH, Linehan WM, Teh BT, Richard S, Zhuang Z. Coexpression of erythropoietin and erythropoietin receptor in von Hippel-Lindau disease-associated renal cysts and renal cell carcinoma. Clin Cancer Res. 2005 Feb 1;11(3):1059-64.
Primary cilia signaling in CNS progenitors and their role in neonatal hydrocephalus. Principal Investigator. K12 Neurosurgeon Research Career Development Program (NRCDP); National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); and Massachusetts General Hospital, Harvard Medical School. Jan 2014 – Jan 2017.
Role of neural progenitor cells in the development of neonatal hydrocephalus. Principal Investigator. Hydrocephalus Association’s CSF Production, Flow and Regulation, Therapeutics and Diagnostics Award. Sep 2013-Sep 2016.
Role of progenitor cells in the development of congenital hydrocephalus. Collaborator. National Institutes of Health. Sep 2013-Sep 2016.
Joshua S. Waxman, PhD
Understanding the molecular underlying nature of congenital heart defects; cardiomyocyte formation
Visit the Waxman Lab.
BA: New College, Sarasota, FL,1999.
PhD: University of Washington, Seattle, WA, 2004.
Postdoctoral Fellow: Skirball Institute/NYU School of Medicine, New York, NY, 2004-2009.
D’Aniello E, Rydeen A, Anderson J, Mandal A, Waxman JS.Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid. PLoS Genet. 2013 Aug; 9(8):e1003689.
Sorrell MR, Dohn TE, D’Aniello E, Waxman JS. Tcf7l1 proteins cell autonomously restrict cardiomyocyte and promote endothelial specification in zebrafish. Dev Biol. 2013;380(2); 199-210.
Mandal A, Rydeen A, Anderson J, Sorrell MR, Zygmunt T, Torres-Vázquez J, Waxman JS. Transgenic retinoic acid sensor lines in zebrafish indicate regions of available embryonic retinoic acid. Developmental Dynamics. 2013 Aug; 242(8); 989-1000.
Dohn TE, Waxman JS. Distinct phases of Wnt/β-catenin signaling direct cardiomyocyte formation in zebrafish. Dev Biol. 2012 Jan 15;361(2):364-76.
Sorrell MR, Waxman JS. Restraint of Fgf8 signaling by retinoic acid signaling is required for proper heart and forelimb formation. Dev. Biol. 2011 Oct 1; 358(1):44-55.
Waxman JS, Yelon D. Zebrafish retinoic acid receptors function as context-dependent transcriptional activators. Dev Biol. 2011; 352:128-40.
Feng L, Hernandez RE, Waxman JS, Yelon D, Moens CB. Dhrs3a regulates retinoic acid biosynthesis through a feedback inhibition mechanism. Dev Biol. 2010 Feb 1;338(1):1-14.
Waxman JS, Yelon D. Increased Hox activity mimics the teratogenic effects of excess retinoic acid signaling. Dev Dyn. 2009 May; 238(5):1207-13.
Linville A, Radtke K, Waxman JS, Yelon D, Schilling TF. Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches. Dev Biol. 2009 Jan 1; 325(1):60-70.
Waxman JS, Keegan BR, Roberts RW, Poss KD, Yelon D. Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish. Dev Cell. 2008 Dec; 15(6):923-34.
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.
Transcription factors; transcriptional regulation; functional genomics; genome analysis
Matthew T. Weirauch, PhD, a faculty member in the Center for Autoimmune Genomics and Etiology (CAGE), is a computational biologist with special emphasis on genomic approaches for studying transcription factor (TF) interactions with DNA, and how genetic variation proximal to these interactions contributes to human diseases. He recently spearheaded large-scale efforts for the experimental and computational determination of sequence binding motifs for eukaryotic TFs (Weirauch et al., Cell, 2014), and RNA binding proteins (Nature co-first author, 2013). He has also been involved in numerous high-profile genomics efforts, including an evaluation of algorithms for TF-DNA recognition (Weirauch et al., Nature Biotech, 2013), and the largest genetic interaction studies performed to date in both C. elegans (Byrne et al., Journal of Biology, 2007) and S. cerevisiae (Costanzo et al., Science, 2010). Recent work in his group focuses on how disease-associated genomic regions affect TF binding, and how these alterations affect disease onset and progression (Wang et al., Mol Cancer., 2010; Qian et al., Pediatr Blood Cancer, 2014; Kottyan et al., Nature Genetics, 2014; Martin et al., Circulation: Cardiovascular Genetics, 2014; Fang et al., Cell Reports, 2014).
The long-term goal of Dr. Weirauch's lab is to create an accurate computational system for predicting TF and RNA binding protein interactions with the genome/transcriptome, and for understanding the effects of genetic variations on these interactions. As it continues to mature, they are applying this system to predict the effects of genetic variants that are strongly associated with several human diseases. Long-term, they envision that this system will be used for personalized medicine-based approaches – given the genome sequence of a patient, it will produce a prioritized list of genetic variants likely to contribute to disease onset via alterations to protein binding events.
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.
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.
Makashir S, Kottyan L, Weirauch M. Meta-analysis of Differential Gene Co-expression: Application to Lupus. Pacific Symposium on Biocomputing. 2014.
Kottyan L, Davis B, Sherrill J, Lui K, Rochman M, Kaufman K, Weirauch M, Vaughn S, Lazaro S, Rupert A, Kohram M, Stucke E, Kemme K, Magnusen A, He H, Dexheimer P, Mukkada V, Putnam P, Strauss A, Abonia JP, Martin L, Harley J, Rothenberg M. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet. 2014 Aug;46(8):895-900.
Sullivan A, Arsovski A, Lempe J, Bubb K, Weirauch M, et al. Mapping and Dynamics of Regulatory DNA and Transcription Factor Networks in A. thaliana.
Cell Reports. 2014 Sep 10.
Kottyan L, Zoller E, Bene J, Lu X, Kelly J, Rupert A, Lessard C, Vaughn S, Marion M, Weirauch M, et al. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share.
Hum Mol Genet. 2014 Sep 8.
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.
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.
Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear E, Sevier C, Ding H, Koh J, Toufighi K, Mostafavi S, Prinz J, St Onge R, VanderSluis B, Makhnevych T, Vizeacoumar F, Alizadeh S, Bahr S, Brost R, Chen Y, Cokol M, Deshpande R, Li Z, Lin Z, Liang W, Marback M, Paw J, San Luis B, Shuteriqi E, Tong A, van Dyk N, Wallace I, Whitney J, Weirauch M, Zhong G, Zhu H, Houry W, Brudno M, Ragibizadeh S, Papp B, Pál C, Roth F, Giaever G, Nislow C, Troyanskaya O, Bussey H, Bader G, Gingras A, Morris Q, Kim P, Kaiser C, Myers C, Andrews B, Boone C. The genetic landscape of a cell. Science. 2010 Jan 22;327(5964):425-31.
Byrne A, Weirauch M, Wong V, Koeva M, Dixon S, Stuart J, Roy P. A global analysis of genetic interactions in Caenorhabditis elegans.
J Biol. 2007;6(3):8.
ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.
Nature. 2007 Jun 14;447(7146):799-816.
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, Basic Research, Division of Endocrinology
Director, Basic Research, Division of Endocrinology
Director, Pluripotent Stem Cell Center
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.
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.
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.
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
Co-Director, Perinatal Institute
Chief, Section of Neonatology, Perinatal and Pulmonary Biology
Cystic fibrosis research; lung morphogenesis; control of gene expression in the respiratory epithelium; gene delivery and therapy
Visit the Whitsett Lab.
Jeffrey A. Whitsett, MD, is chief of the Section of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children's Hospital Medical Center.
Dr. Whitsett received his medical degree from Columbia University, in New York, and has been a faculty member since 1977. He is internationally known for his research in pulmonary medicine, as well as for his clinical expertise in neonatology.
Dr. Whitsett has made a series of groundbreaking contributions in 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.
Throughout his career, Dr. Whitsett has had the remarkable ability to move from molecular biology, to animal models, to diagnosis and therapy of human disease. He played a critical role in making surfactant protein replacement a routine tool for treating immature lungs and respiratory distress syndrome in premature infants. His laboratory has contributed to the identification of a number of genes critical for lung formation and function. Mutations in genes regulating surfactant homeostasis were shown to cause acute and chronic lung disease in infants and adults.
Dr. Whitsett is a member of the Institute of Medicine, National Academy of Sciences and is the recipient of the Mead Johnson Award, a National Institutes of Health (NIH) Merit Award, the first Julius Comroe Lectureship in Pulmonary Research from FASEB, the William Cooper Procter Award from Cincinnati Children's, the Amberson Lecture Award of the American Thoracic Society, the prestigious Daniel Drake Medal for scientific contributions from the University of Cincinnati College of Medicine, the International Arvo Ylppö Medal from the Finnish Foundation for Pediatric Research and the Grand Hamdan International Award on Neonatal Medicine from the United Arab Emirates.
Dr. Whitsett is the author of more than 400 papers in both the basic science and clinical literature.
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.
Sivaprasad U, Askew DJ, Ericksen MB, Gibson AM, Stier MT, Brandt EB, Bass SA, Daines MO, Chakir J, Stringer KF, Wert SE, Whitsett JA, Le Cras TD, Wills-Karp M, Silverman GA, Khurana Hershey GK. A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma. J Allergy Clin Immunol. 2011 Jan;127(1):254-61, 261.e1-6.
Lin SC, Wani MA, Whitsett JA, Wells JM. Klf5 regulates lineage formation in the pre-implantation mouse embryo. Development.2010 Dec;137(23):3953-63.
Suzuki T, Sakagami T, Young LR, Carey BC, Wood RE, Luisetti M, Wert SE, Rubin BK, Kevill K, Chalk C, Whitsett JA, Stevens C, Nogee LM, Campo I, Trapnell BC. Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. Am J Respir Crit Care Med. 2010 Nov 15;182(10):1292-304.
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.
Perl AK, Riethmacher D, Whitsett JA. Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis. Am J Respir Crit Care Med. 2010 Sep 24.
Tompkins DH, Besnard V, Lange AW, Keiser AR, Wert SE, Bruno MD, Whitsett JA. Sox2 Activates Cell Proliferation and Differentiation in the Respiratory Epithelium. Am J Respir Cell Mol Biol. 2010 Sep 20.
Meyer SE, Hasenstein JR, Baktula A, Velu CS, Xu Y, Wan H, Whitsett JA, Gilks CB, Grimes HL. Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival. Am J Pathol. 2010 Sep;177(3):1503-13.
Xu Y, Zhang M, Wang Y, Kadambi P, Dave V, Lu LJ, Whitsett JA. A systems approach to mapping transcriptional networks controlling surfactant homeostasis. BMC Genomics. 2010 Jul 26;11:451.
Sakagami T, Beck D, Uchida K, Suzuki T, Carey BC, Nakata K, Keller G, Wood RE, Wert SE, Ikegami M, Whitsett JA, Luisetti M, Davies S, Krischer JP, Brody A, Ryckman F, Trapnell BC. Patient-derived granulocyte/macrophage colony-stimulating factor autoantibodies reproduce pulmonary alveolar proteinosis in nonhuman primates. Am J Respir Crit Care Med. 2010 Jul 1;182(1):49-61.
Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, Wills-Karp M, Whitsett JA. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010 Jun 1;184(11):6133-41.
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.
Liver development; hepatic fibrosis and cirrhosis; hepatic stellate cells; stem cells and regeneration; congenital biliary diseases; zebrafish genetics
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.
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.