Joseph Schlessinger

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.

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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. ^[1] 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.^[2]

Academic Positions

Joseph 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^[3]. He is a member of the editorial boards of numerous prestigious journals, including Cell (journal)^[4], Molecular Cell.^[5], the Journal of Cell Biology^[6], and the Science (journal) magazine Signal Transduction Knowledge Environment (STKE)^[7].

He has also been the recipient of numerous prizes, including the Michael Landau Prize (1973),^[8] the Sara Leady Prize (1980),^[9][10] the Hestrin Prize (1983)^[11][12][13] the Levinson Prize (1984)^[14], a Ciba-Drew Award (1995)^[15], the Antoine Lacassagne Prize (1995)^[16], the Taylor Prize (2000)^[17][18], and the Dan David Prize (2006).^[19][20] In 2002, he was granted an honorary Doctorate of Philosophy from the University of Haifa,^[21] and has given a long list of named lectures at many institutions^[22], including the Harvey Society (in the 1993-1994 Harvey Lectures series)^[23], and the 2006 Keith R. Porter Lecture of the American Society for Cell Biology^[24].

Before joining Yale, Schlessinger was the Director of the Skirball Institute for Biomolecular Medicine at NYU Medical Center from 1998–2001 and the Milton and Helen Kimmelman Professor and Chairman of the Department of Pharmacology at NYU Medical School from 1990–2001. He 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 at the Weizmann Institute from 1985–1991.^[25]

Publications and Research

According to PubMed, Joseph Schlessinger has authored over 400 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.^[26] 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. 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. ^[27]. His papers have been cited a total of 72,216 times.^[28] A September 2003 article in the UK newspaper 'The Guardian' listed Schlessinger as number 14 in the "Giants of Science."^[29]

Personal life

Joseph Schlessinger was born March 26, 1945, in the village of Topusko in [Yugoslavia]].^[30] Schlessinger is married to Irit Lax, now Associate Research Scientist 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, an area in which Pubmed searches show that she has authored approximately 130 publications, many of them in collaboration with Joseph Schlessinger. Lax has been working for Joseph Schlessinger since she was a graduate student in Israel in the early 1980s. They are married and each has two children from a previous marriage.^[31]

A sexual harassment lawsuit was initiated by Joseph Schlessinger's former secretary, (Mary Beth Garceau v. Yale University). Mary Beth Garceau alleged numerous episodes of sexual harassment by Joseph Schlessinger during her employment at Yale. ^[32],^[33],^[34],^[35]. Mary Beth Garceau claimed that Yale University did nothing to stop Schlessinger's sexual harassment despite her frequent complaints, forcing her to resign. The case was settled out of court in mid-2007, and the terms of the settlement were not disclosed.^[36]

Sugen

Joseph Schlessinger co-founded (with Axel Ullrich and Steven Evans-Freke) the biotechnology company Sugen 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 marketed by Pfizer as Sutent. ^[37] After a priority review, Sutent was FDA approved 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. ^[38] Sugen was acquired by Pharmacia in 1999, which merged with a part of Monsanto 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 ^[39]. 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 withRoche Pharmaceuticals to develop PLX4032 as a targeted anti-cancer therapeutic ^[40]. Plexxikon is also collaborating with Wyeth Pharmaceuticals on several products (centered on PPAR inhibitors) for use in type II diabetes and other metabolic disorders ^[41]. The most advanced of these agents is PLX204, which is currently in Phase 2 clinical trials for type II diabetes ^[42].

Yeda/Aventis/Imclone

Yeda Research and Development Co, Ltd a company set up to commercialize and market the products of research at the Weizmann Institute of Science in Israel^[43], have recently challenged the Aventis-owned patent, licensed by Imclone, for the use of anti-Epidermal growth factor receptor antibodies in combination with chemotherapy, to slow the growth of certain tumors. This is the so-called '866' patent^[44] which was filed in 1989 by Rhone-Poulenc-Rorer, on which Joseph Schlessinger is listed as first-named inventor, although he receives no royalties. ^[45].

Joseph Schlessinger's former colleagues at the Weizmann Institute, in particular Michael Sela, claimed to have come up with this concept alongside Schlessinger when they worked together there there years earlier, and challenged the Aventis patent in the United States. Schlessinger gave court testimony that the idea of combining the anti-EGFR antibody that his lab had developed with chemotherapy was his own idea. However, scientists at the Weizmann Institute provided extensive documentation that they had also been developing this idea with the antibody that Schlessinger had given them^[46][47]. Schlessinger claims to have initiated the idea but had not documented his research and ideas as thoroughly, leaving him forced to rely on his recollections of the patent filing some 17 years before Yeda mounted their challenge.^[48].

According to a Money Magazine article, Judge Naomi Reice Buchwald, the presiding federal judge in this case^[49] dismissed Joseph Schlessinger's testimony. Judge Buchwald was quoted as saying that "The Weizmann scientists have presented documentary evidence substantiating each step of the inventive process, in stark contrast to the dearth of evidence supporting the named inventors' version of events." She went on to describe the Weizmann Institute's corroborating evidence for patent rights as "overwhelming," and of "extraordinary breadth." Judge Buchwald also stated that "...Schlessinger's explanation... (for patent rights) can most generously be described as strained."^[50].

Imclone Systems filed a countersuit in 2006^[51], claiming that the '866' patent is invalid due to the removal by Yeda of the originally named inventors. Imclone is vigorously pursuing this appeal.

References

• Yale School of Medicine appoints Joseph Schlessinger, formerly of NYU, Pharmacology Chair., M2 Presswire, 05-JUN-01.
• Yale Researcher Shares $1 Million Prize
• http://www.med.yale.edu/pharm/chairman/biography.htm

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