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Raphael Kopan, PhD

Director, Division of Developmental Biology

Professor, UC Department of Pediatrics

Phone 513-636-1299

Research

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 developmentDev 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.