Rik Derynck
Professor
Rik Derynck grew up in Bruges, Belgium. He received his undergraduate education and Lic. Sc. in Zoology at the University of Leuven, Belgium. He then moved to the University of Ghent, Belgium, to pursue his Dr. Sc. training under the mentorship of Dr. Walter Fiers. This was around the time that recombinant DNA technology began to emerge and where restriction enzymes were being purified and exchanged, rather than bought. After purifying some restriction enzymes of his own and developing a 2-D system to separate DNA fragments, he cloned the cDNA for human fibroblast interferon, now known as interferon-beta. Its cDNA cloning and subsequent expression in E.coli, published in 1981, received considerable attention due to its potential as an anti-viral therapeutic. He received his Dr. Sc. degree in 1981.
That same year, he moved to the San Francisco Bay Area to join Genentech, one of the first biotech companies, founded by Bob Swanson and Herb Boyer. Genentech was at that point a small company with only 30 or so employees, but has since grown to over 5000 employees. As a scientist in the lab of Dr. David Goeddel, he continued his research on interferon, and also initiated a project that led to the molecular characterization of tumor necrosis factor (TNF).
He
subsequently initiated research aimed at the molecular characterization
of "transforming growth factor" (TGF), whose controversial activity
had just been identified in the secreted medium of some tumor cells,
where it had the ability to induce reversible transformation of fibroblasts
in culture. This research led to the molecular cloning of TGF-alpha
and TGF-beta, which were reported in 1984 and 1985, respectively. Both
growth factors are now considered as prototypes for their respective
families of growth and differentiation factors. Thereafter, the lab
continued to focus on defined aspects of the biology of TGF-alpha and
TGF-beta.
In 1991, he moved his lab to UCSF. He is currently a Professor and Vice Chair in the Department of Cell and Tissue Biology, and Professor in the Department of Anatomy. He is the Director of the Program in Craniofacial and Mesenchymal Biology, and Co-Director of the UCSF Institute for Regeneration Medecine.
Since 1983, our lab has pursued research on the molecular, cell, and tissue biology of TGF-alpha and TGF-beta.
In our TGF-alpha research, we have pursued the characterization of TGF-alpha as a model for the family of TGF-alpha-related proteins. We have been addressing questions related to the normal role of TGF-alpha in development and its role in carcinoma development. Among our past "highlights" are the (1) the cDNA cloning of TGF-alpha; (2) the demonstration that TGF-alpha expression can confer a transformed phenotype and tumorigenesis to normal cells; (3) the observation that TGF-alpha expression is frequently upregulated in carcinomas; (4) the demonstration that TGF-alpha is expressed during normal development (TGF-alpha was thought to be restricted to tumor cells); (5) the functional inactivation of the EGF receptor (i.e. the receptor for TGF-alpha) through targeted gene inactivation, leading to developmental abnormalities consistent with a role of TGF-alpha/EGFR signaling in epithelial maturation; (6) the demonstration that TGF-alpha is made as a transmembrane growth factor, and that transmembrane TGF-alpha is able to activate the EGF receptor (at that time growth factors were thought of as secreted polypeptides); (7) the demonstration that activation of tyrosine kinase receptors by their ligands, and activation of the Erk MAP kinase and/or p38 MAP kinase signaling pathways results in physiological activation of ectodomain shedding of TGF-alpha and other transmembrane proteins. Our current research focuses primarily on the regulation of transmembrane TGF-alpha presentation and shedding by interacting proteins and signaling pathways.
Following the cloning of TGF-beta, now known as TGF-beta1, it became rapidly apparent that TGF-beta1 would serve as prototype for a large TGF-beta superfamily with important roles in normal development and tumor progression. Among the past "highlights" are (1) the cDNA cloning of TGF-beta1, the first member of the TGF-beta superfamily; (2) the cDNA cloning of TGF-beta3; (3) the demonstration that TGF-beta1 expression is often upregulated in tumor development; (4) the demonstration that TGF-beta can induce epithelial-to-mesenchymal transdifferentiation (now considered as an important step for the tumor cell in the acquisition of an invasive phenotype leading to metastasis); (5) the identification of the first type I TGF-beta receptor; (6) the identification of the TGF-beta Smads and their role in TGF-beta-induced transcription; (7) the model for TGF-beta-induced activation of Smads as signaling effectors; (8) the elucidation of important aspects of how TGF-beta-activated Smads induce transcription; (9) the general model for TGF-beta-induced transcription through Smads; (10) the mechanisms of TGF-b-induced transcription repression through Smads; (11) the characterization of the role of TGF-beta signaling in osteoblast differentiation and bone development. We are currently focusing our research on the mechanisms of TGF-beta signaling, the regulation of transcription by Smads, and the role of TGF-beta signaling in mesenchymal differentiation to bone, fat and muscle cells.