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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
Professor, UC Department of Pediatrics
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, 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.
Liu Z, Chen S, Boyle S, Ilagan MX, Zhu Y, Zhang A, Kopan R. The Extracellular Domain of Notch2 Increases its Cell surface Abundance and Ligand Responsiveness During Kidney development. Dev Cell. 2013 Jun 24;25(6):585-98.
Morimoto M, Nishinakamura R, Saga Y, Kopan R. Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells. Development. 2012 Dec 1:139(23): 4365-73.
Demehri S, Turkoz A, Manivasagam S, Yockey LJ, Turkoz M, Kopan R. Elevated Epidermal Thymic Stromal Lymphopoietin Levels Establish An Anti-Tumor Environment In The Skin. Cancer Cell. 2012 Oct;16;22(4): 494–505.
Barak H, Huh SH, Chen S, Jeanpierre C, Martinovic J, Parisot M, Bole-Feysot C, Nitschké P, Salomon R, Antignac C, Ornitz DM, Kopan R. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell. 2012 Jun 12;22(6): 1191-1207.
Boyle SC, Kim M, Valerius MT, McMahon AP, Kopan R. Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in mesenchymal-to-epithelial transition of nephron stem cells. Development. 2011 Oct;138(19): 4245-54.
Ilagan MX, Lim S, Fulbright M, Piwnica-Worms D, Kopan R. Real-time imaging of notch activation with a luciferase complementation-based reporter. Sci Signal. 2011 Jul 12;4(181):rs7.
Liu Z, Turkoz A, Jackson EN, Corbo JC, Engelbach JA, Garbow J, Piwnica-Worms D, Kopan R. Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice. J Clin Invest. 2011 Feb;121(2):800-8.
Liu Z, Schneider DL, Kornfeld K, Kopan R. Simple copy number determination with reference query pyrosequencing (RQPS). Cold Spring Harb Protoc. 2010 Sep 1;2010(9):pdb.prot5491.
Morimoto M, Liu Z, Cheng HT, Winters N, Bader D, Kopan R. Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate. J Cell Sci. 2010 Jan 15;123(Pt2):213-24.
Demehri S, Morimoto M, Holtzman MJ, Kopan R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS Biol. 2009 May 19;7(5): e1000067.
Bruce J. Aronow, PhD Co-director, Computational Medicine Center
Co-director, Computational Medicine Center
Dr. Aronow's research is devoted to 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. His lab is using a variety of available structural and functional genomic and biological systems descriptive data to form models of how biological systems assemble, adapt and become impaired in disease. The lab's overall hypothesis is that by interconnecting as much experimental and observational information as possible, we can gain new insights into the mechanisms by which different biological systems can achieve health or healthy adaptation, or undergo disease processes. More specific, with the co-leadership of Anil Jegga, DVM, the lab is identifying genetic features that control gene expression including cis-elements, trans factors and microRNAs, which normally work together in extended cell, tissue, organ and systems networks to enable development and homeostasis. Alterations of these features can alter phenotypes and increase or decrease disease. Some of the lab's work includes the identification of conserved, diverged and evolved cis-element clusters that are acted on by transcription and chromatin proteins. The lab has developed a Web-based tool called GenomeTraFaC that at present allows discovery of shared cis-elements in conserved non-coding sequences of mice and humans.
Barnes MG, Grom AA, Thompson SD, Griffin TA, Pavlidis P, Itert L, et al. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis and rheumatism. 2009 Jul;60(7):2102-12.
Qu XA, Gudivada RC, Jegga AG, Neumann EK, Aronow BJ. Inferring novel disease indications for known drugs by semantically linking drug action and disease mechanism relationships. BMC Bioinformatics. 2009 May;10 Suppl 5:S4.
Gu Y, Harley IT, Henderson LB, Aronow BJ, Vietor I, Huber LA, et al. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature. 2009 Apr 23;458(7241):1039-42.
Nishijo K, Chen QR, Zhang L, McCleish AT, Rodriguez A, Cho MJ, et al. Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma. Cancer Res. 2009 Apr 1;69(7):2902-11.
Chen J, Aronow BJ, Jegga AG. Disease candidate gene identification and prioritization using protein interaction networks. BMC Bioinformatics. 2009 Feb;10:73.
Shen H, Powers N, Saini N, Comstock CE, Sharma A, Weaver K, et al. The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res. 2008 Dec 15;68(24):10154-62.
Brunskill EW, Aronow BJ, Georgas K, Rumballe B, Valerius MT, Aronow J, et al. Atlas of gene expression in the developing kidney at microanatomic resolution. Developmental cell. 2008 Nov;15(5):781-91.
Mahller YY, Sakthivel B, Baird WH, Aronow BJ, Hsu YH, Cripe TP, et al. Molecular analysis of human cancer cells infected by an oncolytic HSV-1 reveals multiple upregulated cellular genes and a role for SOCS1 in virus replication. Cancer Gene Ther. 2008 Nov;15(11):733-41.
Kucherlapati MH, Yang K, Fan K, Kuraguchi M, Sonkin D, Rosulek A, et al. Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the cecum and proximal colon. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15493-8.
Gudivada RC, Qu XA, Chen J, Jegga AG, Neumann EK, Aronow BJ. Identifying disease-causal genes using Semantic Web-based representation of integrated genomic and phenomic knowledge. J Biomed Inform. 2008 Oct;41(5):717-29.
Samantha A. Brugmann, PhD
is a developmental biologist who aims to understand craniofacial development and elucidate the molecular basis for diseases that affect the craniofacial complex. Furthermore, Dr. Brugmann attempts to understand the forces that help pattern the face during normal and abnormal development she utilizes various model systems with unique facial morphologies.
Visit the Brugmann Lab.
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. She received her BS in cell and molecular biology in 1998 from Tulane University in New Orleans, LA. She then moved to Washington, DC to study cranial sensory placode development in Xenopus laevis at George Washington University. After receiving her PhD in genetics from George Washington University in 2004, she moved to Stanford, CA to do her postdoctoral research in craniofacial development at Stanford University. While at Stanford she received a Ruth L. Kirschstein National Research Service Awards for Individual Postdoctoral Fellows (F32) in 2006, a Pediatric Research Fund-Child Health Research Program Grant in 2009 and a NIH Pathway to Independence Award (K99/R00) in 2010. She joined Cincinnati Children’s Hospital Medical Center in January 2011 to study craniofacial development and disease.
Zaghloul NA, Brugmann SA. The emerging face of primary cilia. Genesis. 2011 Apr;49(4):231-46.
Levi B, James AW, Nelson ER, Brugmann SA, Sorkin M, Manu A, Longaker MT. Role of Indian hedgehog signaling in palatal osteogenesis. Plast Reconstr Surg. 2011 Mar;127(3):1182-90.
Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J. A unique chromatin signature uncovers early developmental enhancers in humans. Nature. 2011 Feb 10;470(7333):279-83.
Cordero DR, Brugmann S, Chu Y, Bajpai R, Jame M, Helms JA. Cranial neural crest cells on the move: their roles in craniofacial development. Am J Med Genet A. 2011 Feb;155(2):270-9. Brugmann SA, Cordero DR, Helms JA. Craniofacial ciliopathies: A new classification for craniofacial disorders. Am J Med Genet A. 2010 Dec;152A(12):2995-3006. Brugmann SA, Allen NC, James AW, Mekonnen Z, Madan E, Helms JA. A primary cilia-dependent etiology for midline facial disorders. Hum Mol Genet. 2010 Apr 15;19(8):1577-92. Brugmann SA, Powder KE, Young NM, Goodnough LH, Hahn SM, James AW, Helms JA, Lovett M. Comparative gene expression analysis of avian embryonic facial structures reveals new candidates for human craniofacial disorders. Hum Mol Genet. 2010 Mar 1;19(5):920-30. Brugmann SA, Goodnough LH, Gregorieff A, Leucht P, ten Berge D, Fuerer C, Clevers H, Nusse R, Helms JA. Wnt signaling mediates regional specification in the vertebrate face. Development. 2007 Sep;134(18):3283-95. Brugmann SA, Kim J, Helms JA. Looking different: understanding diversity in facial form. Am J Med Genet A. 2006 Dec 1;140(23):2521-9. Brugmann SA, Tapadia MD, Helms JA. The molecular origins of species-specific facial pattern. Curr Top Dev Biol. 2006;73:1-42.
Kenneth J. Campbell, PhD
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.
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.
Tiffany Cook, PhD
Understanding the molecular basis of eye development; differentiation of color photoreceptor subtypes in the Drosophila retina; cell-specific regulation of opsin gene expression; mechanisms of cell-specific transcriptional activation and repression
Differentiation of color photoreceptor subtypes in the Drosophila retina; cell-specific regulation of opsin gene expression; mechanisms of cell-specific transcriptional activation and repression
Visit the Cook Lab.
Jukam D, Xie B, Rister J, Terrell D, Charlton-Perkins M, Pistillo D, Gebelein B, Desplan C, Cook T. Opposite network-level feedback in the Hippo pathway for growth regulation and post-mitotic neural fate. Science 2013 Aug 29. [Epub ahead of print]
Riazuddin S, Belyantseva IA, Giese AP, Lee K, Indzhykulian AA, Nandamuri SP, Yousaf R, Sinha GP, Lee S, Terrell D, Hegde RS, Ali RA, Anwar S, Andrade-Elizondo PB, Sirmaci A, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Ahmad W, Khan SN, Akram J, Tekin M, Riazuddin S, Cook T, Buschbeck EK, Frolenkov GI, Leal SM, Friedman TB, Ahmed ZM. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet. 44:1265-71, 2012.
Terrell D, Xie B, Workman M, Mahato S, Zelhof A, Gebelein B, Cook T. OTX2 and CRX rescue overlapping and photoreceptor-specific functions in the Drosophila eye. Dev Dyn. 2012;241(1):215-28.
Charlton-Perkins M, Brown NL, Cook T. Lens in focus: A comparison of lens development in Drosophila and vertebrates. Molec Genet Genom. 2011;286(3-4):189-213.
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 EGF and Notch-dependent signaling. Neural Dev. 2011;6(1):20.
Cook T, Zelhof A, Mishra M, Nie J. 800 Facets of Retinal Degeneration. Prog Mol Biol Transl Sci 2011;100:331-68.
Charlton-Perkins M, Cook TA. Building a Fly Eye: Terminal Differentiation Events of the Retina, Corneal Lens, and Pigmented Epithelia. Curr Top Dev Biol. 2010;93:129-73.
McDonald EC, Xie B, Workman M, Charlton-Perkins M, Terrell DA, Reischl J, Wimmer E, Gebelein B, Cook TA. Multiple transcriptional regulatory domains within Otd control photoreceptor differentiation. Dev Biol. 2010;347:122-32.
Mishra M, Oke A, Lebel C, McDonald EC, Plummer Z, Cook TA, and Zelhof AC. Pph13 and Orthodenticle define a dual regulatory pathway for Drosophila photoreceptor cell morphogenesis and function. Development. 2010;137:2895-904.
Xie B, Charlton-Perkins M, McDonald EC, Gebelein B, Cook TA. Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development. 2007;134:4243-4253.
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. 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.
Andrew Dauber, MD, MMSc Program Director and Director of Translational Research, Cincinnati Center for Growth Disorders
investigates the genetic etiology of growth disorders and other pediatric endocrine conditions. His research employs the latest in genomic technologies to discover novel genetic causes of growth disorders in patients with previously undiagnosed conditions. Further laboratory investigations are then performed to understand the underlying perturbations to growth biology.
Program Director and Director of Translational Research, Cincinnati Center for Growth Disorders
Pediatric endocrinology; growth disorders; precocious puberty
Growth disorders; precocious puberty
MD: Harvard Medical School, Boston, MA, 2000.
MS: Clinical Investigation, Harvard Medical School, Boston, MA 2008.
Residency: Pediatrics, Boston Combined Residency Program in Pediatrics, Boston Children's Hospital and Boston Medical Center, Boston, MA.
Chief Resident: Pediatrics, Boston Children's Hospital, Boston, MA, 2004-2005.
Fellowship: Pediatric Endocrinology, Boston Children's Hospital, Boston, MA.
Certification: Pediatrics, Pediatric Endocrinology
Nilsson O, Guo MH, Dunbar N, Popovic J, Flynn D, Jacobsen C, Lui JC, Hirschhorn JN, Baron J, Dauber A. Short stature, accelerated bone maturation, and early growth cessation due to heterozygous aggrecan mutations. J Clin Endocrinol Metab. 2014 Aug;99(8):E1510-8.
Kerns SL, Guevara-Aguirre J, Andrew S, Geng J, Guevara C, Guevara-Aguirre M, Guo M, Oddoux C, Shen Y, Zurita A, Rosenfeld RG, Ostrer H, Hwa V, Dauber A. A novel variant in CDKN1C is associated with intrauterine growth restriction, short stature, and early-adulthood onset diabetes. Clin Endocrinol Metab. 2014 Jul 24:jc20141949. Epub ahead of print.
Dauber A, Rosenfeld RG, Hirschhorn JN. Genetic Evaluation of Short Stature. J Clin Endocrinol Metab. 2014 Jun 10:jc20141506. Epub ahead of print.
Dauber A, Ercan A, Lee J, James P, Jacobs PP, Ashline DJ, Wang SR, Miller T, Hirschhorn JN, Nigrovic PA, Sackstein R. Congenital disorder of fucosylation type 2c (LADII) presenting with short stature and developmental delay with minimal adhesion defect. Hum Mol Genet. 2014 Jun 1;23(11):2880-7.
Batey L, Moon JE, Yu Y, Wu B, Hirschhorn JN, Shen Y, Dauber A. A novel deletion of IGF1 in a patient with idiopathic short stature provides insight Into IGF1 haploinsufficiency. J Clin Endocrinol Metab. 2014 Jan;99(1):E153-9.
Dauber A, Golzio C, Guenot C, Jodelka FM, Kibaek M, Kjaergaard S, Leheup B, Martinet D, Nowaczyk MJ, Rosenfeld JA, Zeesman S, Zunich J, Beckmann JS, Hirschhorn JN, Hastings ML, Jacquemont S, Katsanis N. SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q24.3 copy-number variant. Am J Hum Genet. 2013 Nov 7;93(5):798-811.
Wang SR, Carmichael H, Andrew SF, Miller TC, Moon JE, Derr MA, Hwa V, Hirschhorn JN, Dauber A. Large-scale pooled next-generation sequencing of 1077 genes to identify genetic causes of short stature. J Clin Endocrinol Metab. 2013 Aug;98(8):E1428-37.
Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN, Gill JC, Cukier P, Thompson IR, Navarro VM, Gagliardi PC, Rodrigues T, Kochi C, Longui CA, Beckers D, de Zegher F, Montenegro LR, Mendonca BB, Carroll RS, Hirschhorn JN, Latronico AC, Kaiser UB. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med. 2013 Jun 27;368(26):2467-75.
Dauber A, Lafranchi SH, Maliga Z, Lui JC, Moon JE, McDeed C, Henke K, Zonana J, Kingman GA, Pers TH, Baron J, Rosenfeld RG, Hirschhorn JN, Harris MP, Hwa V. Novel microcephalic primordial dwarfism disorder associated with variants in the centrosomal protein ninein. J Clin Endocrinol Metab. 2012 Nov;97(11):E2140-51.
Dauber A, Yu Y, Turchin MC, Chiang CW, Meng YA, Demerath EW, Patel SR, Rich SS, Rotter JI, Schreiner PJ, Wilson JG, Shen Y, Wu BL, Hirschhorn JN. Genome-wide association of copy-number variation reveals an association between short stature and the presence of low-frequency genomic deletions. Am J Hum Genet. 2011 Dec 9;89(6):751-9.
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.
Sandra J. F. Degen, PhD Associate Chair for Academic Affairs
studies the regulation of expression of proteins in blood coagulation and growth control: prothrombin and hepatocyte growth factor-like protein, and its membrane tyrosine kinase receptor (Ron).
Associate Chair for Academic Affairs
Vice President for Research, University of Cincinnati
Regulation of expression of proteins in blood coagulation and growth control: prothrombin; hepatocyte growth factor-like protein (HGFL) and its membrane tyrosine kinase receptor (Ron)
Sandra J. F. Degen, PhD, received her BA degree in chemistry from the University of California, San Diego in 1976 and her PhD degree in biochemistry from the University of Washington in 1982.
Following a two year post-doctoral fellowship at the Friedrich Miescher Institute in Basel, Switzerland, she was appointed as an assistant professor of pediatrics at the University of Cincinnati in 1985. She is presently a tenured professor of pediatrics.
The research in Dr. Degen's laboratory focused on two areas of interest that includes blood coagulation and cancer research. Dr. Degen has three patents in this area. Dr. Degen has had continuous grant support since she received her first academic position, and until 2006 was principal investigator on two National Institutes of Health (NIH) grants.
Dr. Degen's honors and awards include being selected as a pew scholar in the biomedical sciences supported by the Pew Memorial Trust, being awarded an Established Investigatorship from the American Heart Association, serving as a regular member of the Hematology II study section at the NIH and being selected to attend the Executive Leadership in Academic Medicine Program for Women in 1997. Most recently she was selected to participate in the Science and Society Institute sponsored by the Pew Scholars Program.
For the University of Cincinnati, she is responsible for all research compliance activities, the animal research program, sponsored research services, sponsored program accounting, entrepreneurial affairs, the intellectual property office, research educational programs and regional, state and federal advocacy with regard to research. More information can be found at the web site for the Office of Research.
Dr. Degen serves on the board of directors of Bio/Start, the Ohio Aerospace Institute, TechSolve and the Oak Ridge Associated Universities.
BA: University of California, San Diego, 1976.
PhD: University of Washington, Seattle, WA, 1982.
Fellowship: Post-doctoral fellowship at the University of Washington in Seattle, WA, 1982-83; post-doctoral Fellowship at the Friedrich Meischer Institute in Basel, Switzerland, 1983-1985.
Mullins ES, Kombrinck KW, Talmage KE, Shaw MA, Witte DP, Ullman JM, Degen SJ, Sun W, Flick MJ, Degen JL. Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain. Blood. 2009 Jan 15;113(3):696-704.Wetzel CC, Leonis MA, Dent A, Olson MA, Longmeier AM, Ney PA, Boivin GP, Kader SA, Caldwell CC, Degen SJ, Waltz SE. Short-form Ron receptor is required for normal IFN-gamma production in concanavalin A-induced acute liver injury. Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G253-61. Kahn JA, Degen SJ, Mansour ME, Goodman E, Zeller MH, Laor T, Lanphear NE, Boat TF. Pediatric faculty members' attitudes about part-time faculty positions and policies to support part-time faculty: a study at one medical center. Acad Med. 2005 Oct;80(10):931-9.Wu J, Wang Y, Xiao W, Meyer KB, Schmidt KM, Morris RE, Degen SJ, La Barbera AR. Assessment of recombinant porcine follicle-stimulating hormone receptor using a novel polyclonal ectodomain antibody. Endocr Res. 2004 May;30(2):269-85.Hess KA, Waltz SE, Toney-Earley K, Degen SJ. The receptor tyrosine kinase Ron is expressed in the mouse ovary and regulates inducible nitric oxide synthase levels and ovulation. Fertil Steril. 2003 Sep;80 Suppl 2:747-54.Peace BE, Hill KJ, Degen SJ, Waltz SE. Cross-talk between the receptor tyrosine kinases Ron and epidermal growth factor receptor. Exp Cell Res. 2003 Oct 1;289(2):317-25.Wetzel CC, Degen SJ, Waltz SE. Cis-acting elements in the hepatocyte growth factor-like protein gene regulate kidney and liver-specific expression in mice. DNA Cell Biol. 2003 May;22(5):293-301.
Hess KA, Waltz SE, Chan EL, Degen SJ. Receptor tyrosine kinase Ron is expressed in mouse reproductive tissues during embryo implantation and is important in trophoblast cell function. Biol Reprod. 2003 Apr;68(4):1267-75. Sun WY, Coleman MJ, Witte DP, Degen SJ. Rescue of prothrombin-deficiency by transgene expression in mice. Thromb Haemost. 2002 Dec;88(6):984-91.Leonis MA, Toney-Earley K, Degen SJ, Waltz SE. Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure. Hepatology. 2002 Nov;36(5):1053-60.
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
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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
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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.
Geraldine Guasch, PhD
Role of stem cells in tumor development; skin cancers; genetics; biochemical studies
Visit the Guasch Lab.
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.
McNairn AJ, Brusadelli M, Guasch G. Signaling moderation: TGF-β in exocrine gland development, maintenance, and regulation. Eur J Dermatol. 2013 Apr 10.
Chang CY, Pasolli HA, Giannopoulou EG, Guasch G, Gronostajski RM, Elemento O, Fuchs E. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature. Mar 7 2013.
McNairn AJ, Doucet Y, Demaude J, Brusadelli M, Gordon CB, Uribe-Rivera A, Lambert PF, Bouez C, Breton L, Guasch G. TGFβ signaling regulates lipogenesis in human sebaceous glands cells. BMC Dermatol. 2013.
McNairn A, Guasch G. Epithelial Transition Zones: merging microenvironments, niches, and cellular transformation. Eur J Dermatol. 2011;21(Suppl.2):21-28. Runck LA, Kramer M, Ciraolo G, Lewis AG, Guasch G. Identification of epithelial label-retaining cells at the transition between the anal canal and the rectum in mice. Cell Cycle. 2010 Aug 1;9(15):3039-45. Guasch G, Schober M, Pasolli HA, Conn EB, Polak L, Fuchs E. Loss of TGF beta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell. 2007 Oct;12(4):313-27.
Guasch G, Fuchs E. Mice in the world of stem cell biology. Nat Genet. 2005 Nov;37(11):1201-6. Review.
Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell. 2004 Mar 19;116(6):769-78. Review.
Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E. Defining the epithelial stem cell niche in skin. Science. 2004 Jan 16;303(5656):359-63.
Rashmi S. Hegde, PhD
Research in the Hegde Laboratory is aimed at understanding the structural basis for specificity in macromolecular interactions. Currently the two main areas of interest in the laboratory are: proteins involved in early vertebrate development; proteins involved in the life- and infection-cycles of the cancer-associated papillomaviruses.
Molecular mechanisms underlying early stages in embryonic organ development; molecular basis of developmental defects and cancer; protein-DNA interactions; X-ray crystallography.
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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 Department of Pediatrics, University of Cincinnati College of Medicine and the Division of Developmental Biology at Children's Hospital Research Foundation.
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.
Korfhagen TR, Kitzmiller J, Chen G, Sridharan A, Haitchi HM, Hegde RS, Divanovic S, Karp CL, Whitsett J. 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.
Tadjuidje E, Hegde RS. The Eyes Absent proteins in development and disease. Cell Mol Life Sci. Sept. 13. 2012. Epub ahead of print.
Riazuddin S, Belyantseva IA, Giese A, Kwanghyuk L, Indzhykulian A, Nandamuri SP, Yousaf R, Lee S, 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 E, Frolenkov GI, Leal SM, Friedman TB, Ahmed ZA. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet. 2012 Sep 30;44(11):1265-71.
Ponferrada VG, Fan J, Vallance JE, Hu S, Mamedova A, Rankin SA, Zorn AM, Hegde RS*, Lang RA.* CRIM1 complexes with ß-catenin and cadherins, stabilizes cell-cell junctions and is critical for neural morphogenesis. PLoS One. 2012;7(3):e32635. *co-corresponding authors.
Riazuddin S, Ahmed ZM, Hegde RS, Khan SN, Nasir I, Shaukat U, Riazuddin S, Butman JA, Griffith AJ, Friedman TB, Choi BY. Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome. BMC Med Genet. 2011 Feb 9;12:21.
Pandey RN, Rani R, Yeo EJ, Spencer M, Hu S, Lang RA, Hegde RS. The Eyes Absent phosphatase-transactivator proteins promote proliferation, transformation, migration, and invasion of tumor cells. Oncogene. 2010;29(25):3715-22.
Xi Z, Zhang Y, Hegde RS, Shakked Z, Crothers DM. Anomalous DNA binding by E2 regulatory protein driven by spacer sequence TATA. Nucleic Acids Res. 2010 Jun;38(11):3827-33.
Miller SJ, Lan ZD, Hardiman A, Wu J, Kordich JJ, Patmore DM, Hegde RS, Cripe TP, Cancelas JA, Collins MH, Ratner N. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene. 2010 Jan 21;29(3):368-79.
Trompette A, Divanovic S, Visintin A, Madan R, Blanchard C, Hegde RS, Wills-Karp M, Gioannini TL, Weiss JP, Karp CL. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature. 2009 Jan 29;457(7229):585-588.
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
Visit the Huppert Lab.
BS: Genetic Biology,Purdue University, West Lafayette, IN, 1992.
PhD: Genetics, Indiana University, Bloomington, IN, 1998.
Postdoctoral Fellow: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2003.
Instructor: Developmental Biology, Washington University School of Medicine, St. Louis, MO, 2005.
Assistant Professor: Cell and Developmental Biology, Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 2012.
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
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.
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.
Lung development; cell proliferation; carcinogenesis; transcriptional regulation of gene expression.
Transcriptional regulation of epithelial and endothelial cell functions during lung embryonic development and lung carcinogenesis; winged helix/forkhead box (Fox) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival; identify and increase understanding of currently unknown mechanisms that cause human lung malformations and promote lung cancer formation.
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. 2013 Nov 11. Epub ahead of print.
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
Yu Lan, PhD
Associate Professor, UC Department of Surgery
Yu Lan, PhD, is a developmental geneticist interested in understanding the genetic basis and developmental mechanisms of structural birth defects. Cleft palate is one of the most common birth defects in humans. To understand the molecular and cellular mechanisms of cleft palate pathogenesis, we have been investigating the molecular pathways governing normal palate development in the laboratory mice.
Through gene expression screening, we have identified several putative transcription factor genes with distinct and dynamic expression patterns in the developing mouse palate. Using the gene targeting technology, we have generated mice carrying null or conditional null mutations in some of these transcription factor genes. Analyses of the mutant mice revealed that several of these transcription factors, such as Osr1 and Osr2, play essential roles in palate development. 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.
Genetic Basis of Cleft Lip and Palate. Co-Investigator. National Institutes of Health. Apr 2003 - Jan 2013. #R01 DE015207.
Molecular Genetic Analysis of Craniofacial Development. Co-Investigator. National Institutes of Health. Apr 2000 - Jun 2015. #R01 DE013681.
Richard A. Lang, PhD Director of the Visual Systems Group
Director of the Visual Systems Group
Wnt Ligands in Tumorigenesis; Vascular Regression and Tissue Regeneration; Lens Induction and Morphogenesis
Visit the Lang Lab.
Carpenter AC, Rao S, Wells JM, Campbell K, Lang RA. Generation of mice with a conditional null allele for Wntless. Genesis. 2010 Sep;48(9):554-8.
Pandey RN, Rani R, Yeo EJ, Spencer M, Hu S, Lang RA, Hegde RS. The Eyes Absent phosphatase-transactivator proteins promote proliferation, transformation, migration, and invasion of tumor cells. Oncogene. 2010 Jun 24;29(25):3715-22.
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.
Smith AN, Radice G, Lang RA. Which FGF ligands are involved in lens induction? Dev Biol. 2010 Jan 15;337(2):195-8.
Chauhan BK, Disanza A, Choi SY, Faber SC, Lou M, Beggs HE, Scita G, Zheng Y, Lang RA. Cdc42- and IRSp53-dependent contractile filopodia tether presumptive lens and retina to coordinate epithelial invagination. Development. 2009 Nov;136(21):3657-67.
Smith AN, Miller LA, Radice G, Ashery-Padan R, Lang RA. Stage-dependent modes of Pax6-Sox2 epistasis regulate lens development and eye morphogenesis. Development. 2009 Sep;136(17):2977-85. Erratum in: Development. 2009 Oct;136(19):3377.
Rao S, Lobov IB, Vallance JE, Tsujikawa K, Shiojima I, Akunuru S, Walsh K, Benjamin LE, Lang RA. Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch. Development. 2007 Dec;134(24):4449-58.
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.
Miller LA, Smith AN, Taketo MM, Lang RA. Optic cup and facial patterning defects in ocular ectoderm beta-catenin gain-of-function mice. BMC Dev Biol. 2006 Mar 15;6:14.
James L. Lessard, PhD
Gene regulation; gene targeting
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.
Kumar A, Crawford K, Flick R, Klevitsky R, Lorenz JN, Bove KE, Robbins J, Lessard JL. Transgenic overexpression of cardiac actin in the mouse heart suggests coregulation of cardiac, skeletal and vascular actin expression. Transgenic Res. 2004 Dec;13(6):531-40.
Szucsik JC, Lewis AG, Marmer DJ, Lessard JL. Urogenital tract expression of enhanced green fluorescent protein in transgenic mice driven by a smooth muscle gamma-actin promoter. J Urol. 2004 Feb;171(2 Pt 1):944-9.
Crawford K, Flick R, Close L, Shelly D, Paul R, Bove K, Kumar A, Lessard J. Mice lacking skeletal muscle actin show reduced muscle strength and growth deficits and die during the neonatal period. Mol Cell Biol. 2002 Aug;22(16):5887-96.
Qian J, Hendrix M, Larsen WJ, Dorn GW 2nd, Lessard JL. Establishment and characterization of a conditionally immortalized smooth muscle/myometrial-like cell line. Mol Reprod Dev. 1997 Jul;47(3):284-94.
Kumar A, Crawford K, Close L, Madison M, Lorenz J, Doetschman T, Pawlowski S, Duffy J, Neumann J, Robbins J, Boivin GP, O'Toole BA, Lessard JL. Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4406-11.
Ng WA, Doetschman T, Robbins J, Lessard JL. Muscle isoactin expression during in vitro differentiation of murine embryonic stem cells. Pediatr Res. 1997 Feb;41(2):285-92.
Qian J, Kumar A, Szucsik JC, Lessard JL. Tissue and developmental specific expression of murine smooth muscle gamma-actin fusion genes in transgenic mice. Dev Dyn. 1996 Oct;207(2):135-44.
Szucsik JC, Lessard JL. Cloning and sequence analysis of the mouse smooth muscle gamma-enteric actin gene. Genomics. 1995 Jul 20;28(2):154-62.
Sawtell NM, Hartman AL, Lessard JL. Conserved tissue-restricted expression of HUC 1-1 actin phenotype among eumetazoan organisms. J Exp Zool. 1990 Oct;256(1):54-62.
Xinhua Lin, PhD
Dr. Xinhua Lin's research is directed toward understanding the mechanisms governing the regulation of cell-cell signaling by extracellular molecules that play essential roles in coordinating cell growth and differentiation. He is focusing particularly on the role of heparan sulfate proteoglycans (HSPGs) in cell-cell signaling and working toward the 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 the Children's Hospital Medical Center of Cincinnati. 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.
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
investigates fundamental mechanisms of development through a combination of quantitative experimental approaches and theoretical and simulation approaches. One major focus of Ma’s lab concerns the questions of how morphogen gradients are established, and how precise positional information is encoded by these gradients and interpreted by cells in developing tissues.
Molecular mechanisms of gene regulation and embryonic development
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.
He F, Saunders TE, Wen Y, Cheung D, Jiao R, ten Wolde PR, Howard M, Ma J. Shaping a morphogen gradient for positional precision. Biophys J. 2010 Aug 4;99(3):697-707.
Deng J, Wang W, Lu LJ, Ma J. A two-dimensional simulation model of the bicoid gradient in Drosophila. PLoS One. 2010 Apr 21;5(4):e10275.
Baird-Titus JM, Clark-Baldwin K, Dave V, Caperelli CA, Ma J, Rance M. The solution structure of the native K50 Bicoid homeodomain bound to the consensus TAATCC DNA-binding site. J Mol Biol. 2006 Mar 10;356(5):1137-51.
Fu D, Ma J. Interplay between positive and negative activities that influence the role of Bicoid in transcription. Nucleic Acids Res. 2005 Jul 19;33(13):3985-93. Print 2005.
Chaney BA, Clark-Baldwin K, Dave V, Ma J, Rance M. Solution structure of the K50 class homeodomain PITX2 bound to DNA and implications for mutations that cause Rieger syndrome. Biochemistry. 2005 May 24;44(20):7497-511.
Ma J. Crossing the line between activation and repression. Trends Genet. 2005 Jan;21(1):54-9.
Fu D, Wen Y, Ma J. The co-activator CREB-binding protein participates in enhancer-dependent activities of bicoid. J Biol Chem. 2004 Nov 19;279(47):48725-33.
Ma J. Actively seeking activating sequences. Cell. 2004 Jan 23;116(2 Suppl):S75-6, 2 p following S76.
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
Pluripotent stem cell biology
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.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.
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.
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 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
Takahisa Nakamura, Alessandro Arduini, Brenna Baccaro, Masato Furuhashi, and Gökhan S. Hotamisligil. Small molecule inhibitors of PKR improve glucose homeostasis in obese, diabetic mice. Diabetes. 2013 In press
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 my research is to understand the mechanisms and evolution of epigenetic events during mammalian reproduction. One of our focus areas is epigenetic regulation of sex chromosomes in germ cell development. Recently, my laboratory demonstrated that DNA damage response pathways trigger epigenetic programming on the sex chromosomes in germ cells. An on-going direction of my laboratory is to pursue a general link between DNA damage response pathways and epigenetic programming. Another goal of my 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.
Broering, T. J.*, Alavattam, K. G.*, Sadreyev, R. I., Ichijima, Y., Kato, Y., Hasegawa, K., Camerini-Otero, R. D., Lee, J. T., Andreassen, P. R., and Namekawa S. H. 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):663-75Namekawa, S. H. Slide preparation method to preserve three-dimensional chromatin architecture of testicular germ cells. J Vis Exp. 2014 Jan 10;(83). 2014Sin, H. S., and Namekawa, S. H. The great escape: active genes on inactive sex chromosomes and their evolutionary implications. Epigenetics, Sep;8(9):887-92. 2013 Sin, H. S., Barski, A., Zhang, F., Kartashov, A. V., Nussenzweig, A., Chen, J., Andreassen, P. R., and Namekawa, S. H. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in postmeiotic spermatids. Genes Dev, Dec 15:26(24)2737-2748. 2012
Ichijima, Y., Sin,H. S., and Namekawa, S. H. Sex chromosome inactivation in germ cells: Emerging roles of DNA damage response pathways. Cell. Mol. Life. Sci, Aug;69(15):2559-72.2012.
Sin, H. S., Ichijima, Y., Koh, E.,Namiki, M., and Namekawa, S. H. Human post meiotic sex chromatin and its impact on sex chromosome evolution. Genome Res, May;22(5):827-36.2012.
Payer, B., Lee, J. T., and Namekawa, S. H. X-inactivation and X-reactivation: Epigenetic hallmarks of mammalian reproduction and pluripotent stem cells. Hum Genet, Aug;130(2):265-80. Epub 2011 Jun 12. 2011.
Ichijima, Y., Ichijima,M., Lou, Z., Nussenzweig, A.,Camerini-Otero,R. D., Chen,J., Andreassen,P. R., and Namekawa, S. H. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes Dev, May 1;25(9):959-71. 2011.
Namekawa, S. H. and Lee, J. T. Detection of nascent RNA, single-copy DNA, and protein localization by immunoFISH in murine germ cells and pre-implantation embryos.Nature Protocols. Feb;6(3):270-84. Epub 2011 Feb 10. 2011.
Namekawa, S. H., Payer, B., Huynh K. D., Jaenisch, R., and Lee, J. T. Two-step imprinted X-inactivation: Repeat vs genic silencing in the mice. Mol Cell Biol Jul;30(13):3187-205. Epub 2010 Apr 19. 2010.
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.
Molecular biology; genetics
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.
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.
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.
Noah F. Shroyer, PhD
is focused on understanding development and diseases of the intestine. He seeks to understand the molecular mechanisms of intestinal epithelial differentiation, and to apply this knowledge to gain insight into major diseases of the intestine such as colon cancer and inflammatory bowel disease.
Visit the Shroyer Lab.
Intestinal epithelial development; colon cancer; inflammatory bowel disease.
BS: Microbiology and Biochemistry, Louisiana State University, Baton Rouge, LA, 1995.
PhD: Cell and Molecular Biology, Baylor College of Medicine, Houston, TX, 2001.
Postdoctoral: Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 2001-2005.
Spence JR, Lauf R, Shroyer NF. Vertebrate intestinal endoderm development. Dev Dyn. 2011 Mar;240(3):501-20.
Kazanjian A, Noah T, Brown D, Burkart J, Shroyer NF. Atonal homolog 1 is required for growth and differentiation effects of notch/gamma-secretase inhibitors on normal and cancerous intestinal epithelial cells. Gastroenterology. 2010 Sep;139(3):918-28, 928.e1-6.
Kohli R, Kirby M, Setchell KD, Jha P, Klustaitis K, Woollett LA, Pfluger PT, Balistreri WF, Tso P, Jandacek RJ, Woods SC, Heubi JE, Tschoep MH, D'Alessio DA, Shroyer NF, Seeley RJ. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G652-60. 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.
Noah TK,Kazanjian A, Whitsett J, Shroyer NF. SAM Pointed Domain ETS Factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells. Exp Cell Res. 2010 Feb;316(3):452-65.
Bossuyt W, Kazanjian A, Aerts S, Leenaerts I, Claeys A, de Geest N, van Kelst S, de Hertogh G, Geboes K, Chuah M, Boivin GP, VandenDriessche T, Marynen P, Cools J, Shroyer NF, Hassan BA. Atonal homolog 1 (Atoh1) is a tumor suppressor gene. PLoS Biology. 2009;7:e39. Kiesslich R, Goetz M, Angus EM, Hu Q, Guan Y, Potten C, Allen T, Neurath MF, Shroyer NF, Montrose MH, Watson AJM. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy: A translational study from mouse to man. Gastroenterology. 2007;133:1769-78.
Shroyer NF, Helmrath MA, Wang VY-C, Antalffy BA, Henning SJ, Zoghbi HY. Intestine specific ablation of Mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology. 2007; 132:2478-88.
Shroyer NF, Wallis Shultz D, Venken KJT, Bellen HJ, Zoghbi HY. Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes and Development. 2005;19:2412-7.
Rolf W. Stottmann, PhD
Developmental neurobiology; genetics; animal models of human congenital defects
Visit the Stottmann Lab
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.
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, in press. 2012.
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 361, 377-391. 2012.
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 138, 4721-4732. 2011.
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.
Kohli V, Rehn K, Sumanas S. Single cell fate mapping in zebrafish. J Vis Exp 56, e3172. 2011.
Proulx K, Lu A, Sumanas S. Cranial vasculature in zebrafish forms by angioblast cluster-derived angiogenesis. Dev Biol. Dec 1;348(1):34-46. 2010.Wong KS, Proulx K, Rost MS, Sumanas S. Identification of vasculature-specific genes by microarray analysis of Etsrp/Etv2 overexpressing zebrafish embryos. Dev Dyn. Jul;238(7):1836-50. 2009.
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;111(9):4500-4510. 2008.
Sumanas S, Lin S. Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLOS Biol. Jan;4(1):e10. 2006.
Sumanas S, Jorniak T, Lin S. Identification of novel vascular endothelial-specific genes by the microarray analysis of the zebrafish cloche mutants. Blood. Jul;106(2):534-541. 2005.
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. 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 Nov 18 Epub. 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.
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. Human pluripotent stem cell-derived gastric organoids: a model of gastric development and Helicobacter pylori infection. Nature. 2014. In press.
Watson CL, Mahe MM, Howell JC, Munera J, Sundaram N, Schweitzer J, Vallance JE, Shroyer NF, Wells JM, Helmrath MA. Human PSC-derived Intestinal Organoids Engraft to Form Mature Human Intestinal Tissue. Nat Med. 2014. In press.
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. JACI. 2014. In press.
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.
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.
KLF5 regulation of intestinal development and stem cell homeostasis. Co-Investigator. National Institutes of Health. Aug 2011 – Jul 2015. NIH 1R01 DK092306-01.
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.
Dan Wiginton, PhD
Gene regulation and development; regulatory factor networks; enhancers; chromatin Modulation
Visit the Wiginton Lab.
Dan Wiginton, PhD, has been in the Department of Pediatrics at Children's Hospital and the University of Cincinnati since 1984. The principal focus of his work during that time has been basic research and research training of graduate students and postdoctoral fellows. Dr. Wiginton's current research interests are directed toward an understanding of the genetic regulatory networks that govern tissue and organ development, as well as the cell-type specific differentiation that underlies this development.
Dr. Wiginton's lab uses the human adenosine deaminase (ADA) gene as a model system to investigate tissue-specific gene expression and the mechanisms that govern it. Transgenic mouse technology has been utilized heavily in these studies, allowing investigation of these questions in vivo. With the ADA model, studies have been carried out to understand thymocyte differentiation in thymus (critical to development of the immune system) and epithelial development in small intestine (critical to normal nutrient utilization).
Prior to coming to Cincinnati, Dr. Wiginton carried out postdoctoral training at the University of Kentucky in Lexington and at the University of Texas Health Sciences Center in San Antonio under Dr. John Hutton. While at these institutions, Dr. Wiginton's research focused on characterization of the normal human ADA protein and gene, and defects in ADA structure and function that cause severe combined immunodeficiency disease(SCID). These studies included collaborations in very early studies directed toward stem cell gene therapy to correct ADA-deficient SCID. Dr. Wiginton carried out his graduate studies at the University of Texas (Austin) under Dr. William Shive. He was awarded a PhD in Biochemistry in 1978, for studies in the area of bacterial enzyme expression and regulation. These studies investigated the biosynthesis and intermediary metabolism of the branched-chain amino acids (valine/leucine/isoleucine).
PhD: The University of Texas at Austin, 1978.
Postdoctoral Fellowship: University of Kentucky, Lexington, KY, 1978-1980.
Fellow / Chemist: Dept. of Hematology, UTHSC-San Antonio and Audie Murphy VA Hospital, San Antonio, TX, 1980-1984.
Dusing MR, Maier EA, Aronow BJ, Wiginton DA. Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine. Physiol Genomics. 2010 Jun;42(1):115-25.
Akeson A, Herman A, Wiginton D, Greenberg J. Endothelial cell activation in a VEGF-A gradient: relevance to cell fate decisions. Microvasc Res. 2010 Jul;80(1):65-74. Maier EA, Dusing MR, Wiginton DA. Temporal regulation of enhancer function in intestinal epithelium: a role for Onecut factors. J Biol Chem. 2006 Oct 27;281(43):32263-71.
Mallory BP, Mead TJ, Wiginton DA, Kulkarni RM, Greenberg JM, Akeson AL. Lymphangiogenesis in the developing lung promoted by VEGF-A. Microvasc Res. 2006 Jul-Sep;72(1-2):62-73.
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.
Yutaka Yoshida, PhD
Molecular mechanisms of neural circuit formation in the developing spinal cord.
Visit the Yoshida Lab.
BS: Keio University, 1994.
PhD: University of Tokyo, 1999.
Postdoctoral fellow: University of Tokyo, 1999-2002; Columbia University, 2002-2007.
Fukuhara K, Imai F, Ladle DR, Katayama K, Leslie JR, Arber S, Jessell TM, Yoshida Y. Specificity of monosynaptic sensory connections imposed by repellent sema3e-plexinD1 signaling. Cell Reports. In press. 2013.
Katayama K, Imai F, Campbell K, Lang RA, Zhneg Y, Yoshida Y. RhoA and Cdc42 are required in pre-migratory progenitors of the medial ganglionic eminence ventricular zone for proper cortical interneuron migration. Development. 140, 3139-3145. 2013.
Katayama K, Leslie JR, Lang RA, Zheng Y, Yoshida Y. Left-right locomotor circuitry depends upon RhoA-driven organization of the neuroepithelium in the developing spinal cord. Journal of Neuroscience. 2012 Jul 25;32(30):10396-407.
Leslie JR, Imai F, Fukuhara K, Takegahara N, Rizvi TA, Friedel RH, Wang F, Kumanogoh A, Yoshida Y. Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of changing semaphorin6D signaling inhibit synapse formation. Development. 2011. Katayama K, Melendez J, Baumann JM, Leslie JR, Chauhan BK, Nemkul N, Lang RA, Kuan CY, Zheng Y, Yoshida Y. Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation. Proc Natl Acad Sci U S A. May 3;108(18):7607-12. 2011.
Pecho-Vrieseling E, Sigrist M, Yoshida Y, Jessell TM, and Arber S. Specificity of Monosynaptic Sensory-Motor Connections Encoded by Sema3e-PlexinD1. Nature. 459:842-6. 2009.Yoshida Y, Han B, Mendelsohn M, Jessell TM. PlexinA1 signaling directs the segregation of proprioceptive sensory axons in the developing spinal cord. Neuron. 52:775-88. 2006.Gu C*, Yoshida Y*, Livet J., Reimert DV, Mann F, Merte J, Henderson CE, Jessell TM, Kolodkin AL, Ginty DD. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science. 307:265-8. 2005. (* denotes equal contribution)
Yoshida Y, Nakamura T, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, Miyasaka T, Yoshida EH, Umemori H, Kunisaki RK, Tani K, Ishii S, Mori S, Suganuma M, Noda T, Yamamoto T. Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes Dev. 17:1201-6. 2003.Yoshida Y, Tanakam S, Umemori H, Minowa O, Usui M, Ikematsu N, Hosoda E, Imamura T, Kuno J, Yamashita T, Miyazono K, Noda M, Noda T, Yamamoto T. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell. 103:1085-97. 2000.
Aaron M. Zorn, PhD Associate Director, Digestive Health Center
Associate Director, Digestive Health Center
Development of lung, liver, pancreas and gastrointestinal tract; vertebrate embryology
Visit the Zorn Lab Site.
BSc University of Toronto, Canada.
PhD University of Texas, Austin, Texas, 1995.
Postdoctoral Wellcome Trust Cancer Research Campaign Institute, University of Cambridge, Cambridge, England, 1996-1999.
Research Fellow Wellcome Trust Gurdon Institute, Universtiy of Cambridge, Cambridge, England, 1999-2002.
Harold Kalter, PhD
Emeritus, University of Cincinnati College of Medicine
William J. Scott, DVM, PhD
DVM: University of Georgia, Athens, GA, 1961.
PhD: Anatomy, George Washington University, Washington, DC, 1969.
Ernest F. Zimmerman, PhD
Emeritus, UC Department of Pediatrics
Role of oxygen free radicals in teratogenesis; diabetic embryopathy and cocaine-induced birth defects.
Dr. Ernest Zimmerman's laboratory studies the role of oxygen free radicals produced by drugs or maternal factors to induce congenital malformations.
Current research is exploring whether oxidative stress is a causative factor in the pathogenesis of diabetic embryopathy. Employing the Splotch mutation in a mouse model, experiments are testing whether diabetes-induced oxidative stress decreases activity of the Pax-3 protein via a redox control mechanism. Thus, the function of the endogenous Pax-3 protein would be additively inhibited by the heterozygous Splotch genotype and oxidative decrease of Pax-3 activity by diabetes.
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