Research Summary
My research goes back to the early days of recombinant DNA, when it was discovered that cDNA could be made in vitro using mRNA as template, when the first restriction enzymes were had to be purified (and exchanged) before starting your research, and when one did not yet have scenarios on how to express a foreign gene from a plasmid in bacteria. As a graduate student, I initiated research that deviated from the overall scope of the host lab and led to the cDNA cloning and bacterial expression of fibroblast interferon, now known as interferon-β. The impact of this research was very substantial, and occurred at the time that cDNA cloning of some proteins with therapeutic potential led to the formation of the first biotechnology companies. This interferon was then developed as a therapy by Biogen and is now clinically used. I moved in 1981 into Genentech, where I started research that led to the characterization of transforming growth factors, i.e. TGF-α and TGF-β, which rapidly became prototypes for their respective families. TGF-α is a transmembrane growth factor, as are the other growth factors in that family, and was originally thought to only act in carcinomas. My lab had a research program on the biology of TGF-α for more than 20 years. I also showed through cDNA cloning that TGF-β was very different from TGF-α. TGF-β, now known as TGF-β1, is the founding member of a large family of differentiation factors of high relevance in developmental and cancer biology, and immunology.
During the last 30 years, my lab made many key contributions to this now extensive research area on the biology of the TGF-β family. My lab was instrumental in identifying the TGF-β receptors and Smads and the mechanisms of Smad signaling and transcriptional control, and has also been playing a key role in the characterization of non-Smad mechanisms of TGF-β signaling. My lab also discovered that TGF-β induces epithelial-mesenchymal differentiation (which was initially highly controversial), and has been pursuing underlying mechanisms after the TGF-β signaling mediators were identified and starting to be characterized. My lab is seen as a leader in the TGF-β field, having contributed in major ways since its inception. Many mechanistic and conceptual advances in the field originate from my lab.
Research Funding
April 1, 2016 - March 31, 2021 - Central role of ShcA in differential TGF-beta signaling, epithelial plasticity and carcinoma cell behavior, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA198179
January 1, 2009 - December 31, 2018 - Regulatory non-Smad signaling in TGF-b-induced epithelial-mesenchymal transition, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA136690
March 1, 1982 - May 31, 2015 - Bio-Organic Biomedical Mass Spectrometry Resource, Co-Investigator. Sponsor: NIH, Sponsor Award ID: P41RR001614
January 1, 1995 - January 31, 2015 - Functional crosstalk of TGF-beta/Smad signaling with methyl transferases, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA063101
Education
University of Louvain, Belgium, Lic.Sc.(M.Sc.), 1974, Zoology
University of Ghent, Belgium, Ph.D., 1981, Molecular Biology