Raphael KopanDepartment of Developmental Biology, Washington University in St Louis, St Louis, MO, USA F1000 Faculty Member (since 03 October 2003)
Professor, Department of Developmental Biology and the Department of Medicine (Division of Dermatology), Washington University in St Louis
1981 BS Biology, Tel-Aviv University, Tel-Aviv, Israel
1984 MS Zoology, Tel-Aviv University, Tel-Aviv, Israel
1989 PhD Molecular Biology, University of Chicago
1990-1994, Postdoctoral Training with Dr Harold Weintraub, Fred Hutchinson Cancer Research
HONORS AND AWARDS:
1981-1984 Recipient of Scholastic awards, Tel-Aviv University
1987-1989 Recipient of Student Travel Award of the American Society of Cell Biology
1988-1989 William Rainey Harper Fellowship
1990-1993 Jane Coffin Childs Memorial Fund for Medical Research Postdoctoral Fellowship
1993-1996 Leukemia Society of America Fellowship
1999- 2001 Zenith Fellows Award from the Alzheimer's Association
2004 Recipient of Marcus Singer Medal
When thinking about the origins of cell-type or species diversity, a central realization is that only 8 signaling pathways (Notch, Wnt, HH, TGF, RTK, GPCR, NFkB and Jak/Stat) allow near infinite number of variations. My lab demonstrated that Notch signaling is propagated through release of its intracellular domain, which acts as a nuclear transcription factor. Notch mediates short-range signals leading to inhibition or promotion of a cellular function in cells that experience Notch activation. Our lab continues to focus on Notch signaling as our lead into attaining a functional understanding of diversity. Our long-term goal is to contribute to efforts aimed at organ formation in vitro from adult or embryonic stem cells. Our efforts are split into two broad focus areas.
We are testing the integration of Notch with additional signaling pathways via high throughput screening of siRNA and chemical libraries in assays our lab has developed. Using genetic engineering, we are manipulating mouse embryos to create new Notch alleles with which to address critical questions regarding redundancy of Notch paralogs and decipher the circuit logic of Notch signaling in mammalian organogenesis. Our main efforts are aimed at comparing and contrasting the activity of Notch signaling in development, maintenance and disease of two organs the skin and the metanephric kidney. The epidermis and hair follicle are both model systems for the study of cell diversity at the tissue level; the vertebrate skin as a whole combines many advantages for our studies. It differentiates properly only as a result of mesenchymal-epithelial interactions and responds to hormonal signals. Many known signaling pathways are active in skin differentiation and most importantly, the skin can tolerate disruption. The kidney offers many of the same advantages regarding integration of signals. It is a glandular-type model involving mesenchymal-epithelial transition and its strength includes well-developed organ-culture techniques. Our lab is currently attempting to perfect siRNA, virus and cDNA delivery into cultured kidney anlagen.
A second focus of my lab is to understand the molecular basis of intramembrane proteolysis. We use biochemical, genetic and high throughput approaches to understand substrate selection and discrimination and the use of RIP in development and disease.
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