Raphael Kopan, PhD

Director, Division of Developmental Biology
Professor, UC Department of Pediatrics

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About

Biography

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

Interests

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

Research Areas

Developmental Biology

Publications

Progenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis. Jarmas, AE; Brunskill, EW; Chaturvedi, P; Salomonis, N; Kopan, R. Nature Communications. 2021; 12.

Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor. Kuang, Y; Pyo, A; Eafergan, N; Cain, B; Gutzwiller, LM; Axelrod, O; Gagliani, EK; Weirauch, MT; Kopan, R; Kovall, RA; et al. PLoS Genetics. 2021; 17.

Increasing mTORC1 Pathway Activity or Methionine Supplementation during Pregnancy Reverses the Negative Effect of Maternal Malnutrition on the Developing Kidney. Makayes, Y; Resnick, E; Hinden, L; Aizenshtein, E; Shlomi, T; Kopan, R; Nechama, M; Volovelsky, O. Journal of the American Society of Nephrology : JASN. 2021; 32:1898-1912.

Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets. Hass, MR; Brissette, D; Parameswaran, S; Pujato, M; Donmez, O; Kottyan, LC; Weirauch, MT; Kopan, R. PLoS Genetics. 2021; 17.

The Rhesus Macaque Serves As a Model for Human Lateral Branch Nephrogenesis. Schuh, MP; Alkhudairy, L; Potter, A; Potter, SS; Chetal, K; Thakkar, K; Salomonis, N; Kopan, R. Journal of the American Society of Nephrology : JASN. 2021; 32:1097-1112.

Notch dimerization and gene dosage are important for normal heart development, intestinal stem cell maintenance, and splenic marginal zone B-cell homeostasis during mite infestation. Kobia, FM; Preusse, K; Dai, Q; Weaver, N; Hass, MR; Chaturvedi, P; Stein, SJ; Pear, WS; Yuan, Z; Kovall, RA; et al. PLoS Biology. 2020; 18.

Notch signaling regulates Akap12 expression and primary cilia length during renal tubule morphogenesis. Mukherjeel, M; Ratnayake, I; Janga, M; Fogarty, E; Scheidt, S; Grassmeyer, J; DeRiso, J; Chandrasekar, I; Ahrenkiel, SP; Kopan, R; et al. FASEB Journal. 2020; 34:9512-9530.

Enhancer architecture sensitizes cell specific responses to Notch gene dose via a bind and discard mechanism. Kuang, Y; Golan, O; Preusse, K; Cain, B; Christensen, CJ; Salomone, J; Campbell, I; Okwubido-Williams, FV; Hass, MR; Yuan, Z; et al. eLife. 2020; 9.

Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors. Seymour, PA; Collin, CA; Egeskov-Madsen, AL R; Jorgensen, MC; Shimojo, H; Imayoshi, I; de Lichtenberg, KH; Kopan, R; Kageyama, R; Serup, P. Developmental Cell. 2020; 52:731-747.e8.

Hamartin regulates cessation of mouse nephrogenesis independently of Mtor. Volovelsky, O; Nguyen, T; Jarmas, AE; Combes, AN; Wilson, SB; Little, MH; Witte, DP; Brunskill, EW; Kopan, R. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115:5998-6003.