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.

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. He is a member of the Editorial Boards of numerous prestigious journals, including Cell and Molecular Cell. Schlessinger 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 top institutions.

Prior to joining Yale University, Joseph Schlessinger was the Director of the Skirball Institute for Biomolecular Medicine at New York University (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.

Education and Training

Joseph 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 Webb). From 1977–1978, Schlessinger was a visiting fellow in the immunology branch of the National Cancer Institute of NIH.

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.. 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. . His papers have been cited a total of 72,216 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 in Yugoslavia. Schlessinger is married to Irit Lax who was recently promoted to 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.

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 . 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 . 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, Joseph Schlessinger co-founded Plexxikon with Professor Sung-Hou Kim of the University of California, Berkeley. Plexxikon was founded in 2001, and uses a pioneering structural biology-based platform to drive the rapid discovery of novel drugs for several different targets . 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 . 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 .

Yeda/Aventis/Imclone Patent Controversy

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, 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 which was filed in 1989 by Rhone-Poulenc-Rorer, on which Joseph Schlessinger is listed as first-named inventor, although he receives no royalties from Imclone or Aventis .

Joseph Schlessinger's former colleagues at the Weizmann Institute in Israel, in particular Michael Sela, claimed to have come up with this concept alongside Joseph Schlessinger when he worked there years ago, and challenged the Aventis patent at district court in the United States. Joseph Schlessinger gave testimony in court that stated the idea of the drug was his idea alone. However, scientists at the Weizmann Institute provided extensive scientific documentation and testimony that they had also been developing the idea for years prior. Joseph Schlessinger claims to have had 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.

According to a Money Magazine article, Judge Naomi Reice Buchwald, the presiding federal judge in this case, dismissed Joseph Schlessinger's testimony as "'not credible,' 'contorted,' 'incredible' and 'wholly unsubstantiated by any contemporaneous records.'" . The article continued on to quote Judge Buchwald as stating 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 as "overwhelming," and of "extraordinary breadth." "...Schlessinger's explanation... can most generously be described as strained," Judge Buchwald wrote in her opinion..

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

Sexual Harassment Lawsuit

The complaint, initiated by Joseph Schlessinger's former secretary, (Mary Beth Garceau v. Yale University) alleged Joseph Schlessinger initiated numerous conversations with her about sex, bragged to her about the number of women he had slept with, claiming the number came to 46, told jokes about penis size and commented on the size of her breasts and style of her underwear.

Mary Beth Garceau also claimed during her first months at the department of pharmacology, according to the complaint, Joseph Schlessinger told her about his sexual infidelity during his business travels. In several incidents over the next year, Joseph Schlessinger showed Mary Beth Garceau pictures of naked women and, on one occasion, a hard-core pornography Web site, the complaint alleged.

Garceau claims that Yale University did nothing to stop the sexual harassment despite her frequent complaints, forcing her to resign because of the situation. A spokesperson for Yale University initially told the Yale Daily News in an interview that "they'll fight the suit in court." Several months later on however, the case between Yale and Garceau was settled out of court for an undisclosed dollar amount, indicating that neither party wished to take the issue to trial