Joseph Schlessinger - Misplaced Pages

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Joseph Schlessinger, Ph.D. is Chair of the Pharmacology Department at Yale University School of Medicine in New Haven, Connecticut. His area of research is signaling through tyrosine phosphorylation, which is important in many areas of cellular regulation, especially growth control and cancer. Schlessinger is best known for his pioneering studies that have led to an understanding of the mechanism of transmembrane signaling by receptor tyrosine kinases and how the resulting signals are transmitted within the cell to control cell growth and differentiation.

Education and Training

Schlessinger received his B.Sc. degree in Chemistry and Physics in 1968 (magna cum laude), plus an M.Sc. degree in chemistry (also magna cum laude) in 1970 from the Hebrew University in Jerusalem. He obtained his Ph.D. degree in biophysics from the Weizmann Institute of Science in 1974. From 1974–1976, he was a postdoctoral fellow in the Departments of Chemistry and Applied Physics at Cornell University, in Ithaca, New York (working with Elliot Elson and Watt W. Webb). From 1977–1978, he was a visiting fellow in the immunology branch of the NIH National Cancer Institute.

Academic Positions

Schlessinger was a member of the faculty of the Weizmann Institute from 1978–1991, and was the Ruth and Leonard Simon Professor of Cancer Research in the Department of Immunology there from 1985 till 1991. In addition, he was a Research Director for Rorer Biotechnology in King of Prussia, Pennsylvania from 1985-1990. In 1990, Schlessinger was appointed as the Milton and Helen Kimmelman Professor and Chairman of the Department of Pharmacology at NYU Medical School. While at NYU School of Medicine, he served as Director of the Skirball Institute for Biomolecular Medicine at NYU Medical Center from 1998–2001 .

Schlessinger has been the William H. Prusoff Professor and Chairman of the Department of Pharmacology at Yale University School of Medicine since 2001. He was elected to the National Academy of Sciences in 2000, and to the American Academy of Arts and Sciences in 2001, and was elected as a Member of the Institute of Medicine in 2005. He is a member of the editorial boards of several journals, including Cell, Molecular Cell., the Journal of Cell Biology, and the new Science magazine 'Science Signaling' journal .

He has also been the recipient of numerous prizes, including the Michael Landau Prize (1973), the Sara Leady Prize (1980), the Hestrin Prize (1983) the Levinson Prize (1984), a Ciba-Drew Award (1995), the Antoine Lacassagne Prize (1995), the Taylor Prize (2000), and the Dan David Prize (2006). In 2002, he was granted an honorary Doctorate of Philosophy from the University of Haifa, and has given a long list of named lectures at many institutions, including the Harvey Society (in the 1993-1994 Harvey Lectures series), and the 2006 Keith R. Porter Lecture of the American Society for Cell Biology. In 2009, Joseph Schlessinger was elected as a Member of the Croatian Academy of Sciences and Arts

Publications and Research

According to PubMed, Joseph Schlessinger has authored over 450 scientific original and review articles in the area of pharmacology, molecular biology, biochemistry, and structural biology. Joseph Schlessinger is an expert in the area of tyrosine kinase signaling. Tyrosine kinase signaling plays a critical role in the control of many cellular processes including cell proliferation, differentiation, metabolism, as well as cell survival and migration. Tyrosine kinases play a particularly important role in cancer, and several agents that block their activity are now used as anti-cancer drugs, such as Imatinib, or Gleevec. Among Schlessinger's contributions are the findings that cell surface receptors with tyrosine kinase activity signal across membrane by forming dimers when they bind to their growth factor activators. He discovered this in studies of the epidermal growth factor receptor (EGFR). He was also instrumental in understanding how the SH2 domain controls tyrosine kinase signaling by binding to phosphorylated tyrosines in activated receptors. One of the seminal findings in this work was the Schlessinger laboratory's cloning of Grb2 and other Adaptor proteins. Another is the lab's cloning of FRS2, which is critical for signaling by the Fibroblast growth factor receptor. In 2001, Schlessinger was ranked by the ISI as one of the world's top 30 most cited scientists (across all fields) in the 1990s. . His papers have been cited a total of 76,699 times. A September 2003 article in the UK newspaper 'The Guardian' listed Schlessinger as number 14 in the "Giants of Science."

Personal life

Joseph Schlessinger was born March 26, 1945, in the village of Topusko, now in Croatia, when it was occupied by Nazi Germany. The family moved to Israel in 1948. . Schlesinger served his compulsory military service with the Golani infantry brigade and was commissioned an officer. As part of his reserve duty he participated in the Six Day War and the Yom Kippur War.

Schlessinger is married to Irit Lax, an Associate Professor in the Pharmacology Department at Yale. She was previously an Assistant Professor in the Pharmacology Department at NYU Medical Center. The focus of her research is on the fibroblast growth factor (FGF) receptor. Lax has been working together with Joseph Schlessinger since she was a graduate student in Israel in the early 1980s. They each have two children from a previous marriage.

In 2006, a sexual harassment lawsuit was initiated against Yale University by Joseph Schlessinger's former secretary, Mary Beth Garceau. Garceau alleged numerous episodes of harassment by Joseph Schlessinger during her employment at Yale, ,,,. and claimed that Yale University failed to act upon her frequent complaints, thus causing Garceau to resign. The case was settled out of court in mid-2007, and the terms of the settlement were not publicly disclosed.

SUGEN

Joseph Schlessinger co-founded (with Axel Ullrich and Steven Evans-Freke) the biotechnology company SUGEN (later acquired by Pfizer in 1991, with the idea of developing anti-cancer therapeutics. In particular, the focus was on ATP-like molecules that would compete with ATP for binding to the catalytic site of receptor tyrosine kinases. This concept has led to the development of an important small-molecule tyrosine kinase inhibitor called Sunitinib. This drug is now marketed by Pfizer as Sutent. After a priority review, Sutent was approved by the FDA in 2006 (in less than 6 months) for use in treating renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). The FDA approval of Sutent marked the first time that the agency had ever approved a new oncology product for two indications simultaneously. SUGEN was acquired by Pharmacia in 1999, which merged with a part of Monsanto Company in 2000, and was finally acquired by Pfizer in 2003.

Sutent/Sunitinib (formerly SU11248) is a small-molecule tyrosine kinase inhibitor that inhibits several receptor tyrosine kinases including the platelet derived growth factor receptor (PDGFR), vascular endothelial growth factor receptors (VEGF-R), c-Kit (the receptor for stem cell factor), and others. Its mechanism of action in cancer treatment involves simultaneous inhibition of angiogenesis and tumor cell proliferation, reducing tumor vascularization and promoting cell death.

Plexxikon

Following his involvement in SUGEN, Schlessinger co-founded Plexxikon with Professor Sung-Hou Kim of the University of California, Berkeley. Plexxikon, founded in 2001, uses a pioneering structural biology-based platform to drive the rapid discovery of novel drugs for several different targets . Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform is now being applied to build a pipeline of product opportunities in multiple therapeutic areas. This discovery process integrates multiple state-of-the-art technologies, including structural screening as one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds in varied disease areas addressing significant unmet needs in each therapeutic category. One of the most advanced drugs under development at Plexxikon is an inhibitor of an activated form of the B-Raf kinase. A V600E mutant of the B-Raf kinase is found in approximately 70% of malignant melanomas, a large percentage of colorectal and thyroid cancers and many other tumor types. PLX4032 selectively inhibits this form of the kinase, and is currently in clinical trials. Plexxikon has entered into a partnership with Roche Pharmaceuticals to develop PLX4032 as a targeted anti-cancer therapeutic , which has shown particular promise for treating melanoma . Plexxikon is also collaborating with Wyeth Pharmaceuticals on several products (centered on PPAR inhibitors) for use in type II diabetes and other metabolic disorders . The most advanced of these agents is PLX204, which is currently in Phase 2 clinical trials for type II diabetes .

References

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