Joseph Schlessinger
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Joseph Schlessinger (born Josip Schlessinger; 26 March 1945) is a Yugoslav-born Israeli- American biochemist and biophysician. He is chair of the Pharmacology Department at
Yale University Yale University is a Private university, private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the List of Colonial Colleges, third-oldest institution of higher education in the United Sta ...
School of Medicine in
New Haven New Haven is a city in the U.S. state of Connecticut. It is located on New Haven Harbor on the northern shore of Long Island Sound in New Haven County, Connecticut and is part of the New York City metropolitan area. With a population of 134,023 ...
, Connecticut, as well as the founding director of the school's new Cancer Biology Institute. His area of research is signaling through
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
phosphorylation, which is important in many areas of cellular regulation, especially growth control and cancer. Schlessinger's work has led to an understanding of the mechanism of transmembrane signaling by receptor
tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...
s and how the resulting signals control cell growth and differentiation.


Biography

Josip Schlessinger was born in
Topusko Topusko is a municipality in Sisak-Moslavina County, Croatia. Topusko is an underdeveloped municipality which is statistically classified as the First Category Area of Special State Concern by the Government of Croatia. Demographics The populati ...
to Jewish parents. His father, Imre, was from Slatina; Imre's first wife and child had been deported to Auschwitz. Schlessinger's mother Rivka was from
Bugojno Bugojno ( sr-cyrl, Бугојно) is a town and municipality located in Central Bosnia Canton of the Federation of Bosnia and Herzegovina, an entity of Bosnia and Herzegovina. It is situated on river Vrbas, to the northwest from Sarajevo. Ac ...
; her first husband had been murdered by the
Ustaše The Ustaše (), also known by anglicised versions Ustasha or Ustashe, was a Croatian fascist and ultranationalist organization active, as one organization, between 1929 and 1945, formally known as the Ustaša – Croatian Revolutionary Move ...
. Imre and Rivka met in a labor camp in 1943 on the Adriatic island of
Rab Rab âːb( dlm, Arba, la, Arba, it, Arbe, german: Arbey) is an island in the northern Dalmatia region in Croatia, located just off the northern Croatian coast in the Adriatic Sea. The island is long, has an area of and 9,328 inhabitants (2 ...
and joined a group of Jewish Partisans. When Schlessinger was born on 26 March 1945 he was wrapped in a British military parachute. He was named for his grandfather. After World War II the family moved to Osijek, where another son, Darko David, was born. Imre Schlessinger once made a joke at the expense of
Tito Tito may refer to: People Mononyms * Josip Broz Tito (1892–1980), commonly known mononymously as Tito, Yugoslav communist revolutionary and statesman * Roberto Arias (1918–1989), aka Tito, Panamanian international lawyer, diplomat, and journ ...
and was sentenced to several months in jail.Ha-Kol (Glasilo Židovske zajednice u Hrvatskoj); Joseph Schlessinger odlikovan visokim Hrvatskim odličjem; stranica 54; broj 111, listopad/rujan 2009. The family moved to Israel in 1948. Schlessinger served his compulsory military service with the Golani Brigade and was commissioned an officer. As part of his reserve duty he participated in the
Six-Day War The Six-Day War (, ; ar, النكسة, , or ) or June War, also known as the 1967 Arab–Israeli War or Third Arab–Israeli War, was fought between Israel and a coalition of Arab states (primarily Egypt, Syria, and Jordan) from 5 to 10 Ju ...
and the
Yom Kippur War The Yom Kippur War, also known as the Ramadan War, the October War, the 1973 Arab–Israeli War, or the Fourth Arab–Israeli War, was an armed conflict fought from October 6 to 25, 1973 between Israel and a coalition of Arab states led by E ...
. Schlessinger received his BSc degree in Chemistry and
Physics Physics is the natural science that studies matter, its fundamental constituents, its motion and behavior through space and time, and the related entities of energy and force. "Physical science is that department of knowledge which r ...
in 1968 (magna cum laude), and an MSc degree in chemistry (also magna cum laude) in 1970 from the Hebrew University of Jerusalem. He obtained his PhD degree in
biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. ...
from the
Weizmann Institute of Science The Weizmann Institute of Science ( he, מכון ויצמן למדע ''Machon Vaitzman LeMada'') is a public research university in Rehovot, Israel, established in 1934, 14 years before the State of Israel. It differs from other Israeli unive ...
in 1974. From 1974 to 1976, he was a postdoctoral fellow in the Departments of Chemistry and Applied Physics at
Cornell University Cornell University is a private statutory land-grant research university based in Ithaca, New York. It is a member of the Ivy League. Founded in 1865 by Ezra Cornell and Andrew Dickson White, Cornell was founded with the intention to tea ...
in
Ithaca, New York Ithaca is a city in the Finger Lakes region of New York, United States. Situated on the southern shore of Cayuga Lake, Ithaca is the seat of Tompkins County and the largest community in the Ithaca metropolitan statistical area. It is named ...
, working with Watt W. Webb, among others. From 1977 to 1978, he was a visiting fellow in the immunology branch of the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
.


Personal life

He is married to Irit Lax, an associate professor in the Pharmacology Department at Yale. They each have two children by previous marriages. In a 2009 interview with a Croatian daily newspaper '' Jutarnji list'', he said, "Basically I am atheist. I grew up Jewish and I truly belong to the Jewish culture, but I'm not a follower of any world religion. Religion does not interest me at all."


Academic career

Schlessinger was a member of the faculty of the Weizmann Institute from 1978 to 1991 and was the Ruth and Leonard Simon Professor of Cancer Research in the Department of
Immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see the ...
from 1985 to 1991. In addition, he was a Research Director for Rorer Biotechnology in
King of Prussia, Pennsylvania King of Prussia (also referred to as KOP) is a census-designated place in Upper Merion Township in Montgomery County, Pennsylvania, United States. As of the 2020 census, its population was 22,028. The community took its unusual name in the 18th ...
, from 1985 to 1990. In 1990, he was appointed as the Milton and Helen Kimmelman Professor and Chairman of the Department of Pharmacology at the
New York University School of Medicine NYU Grossman School of Medicine is a medical school of New York University, a private research university in New York City. It was founded in 1841 and is one of two medical schools of the university, with the other being the Long Island School of ...
. He served as Director of NYU Medical Center's Skirball Institute for Biomolecular Medicine, from 1998 to 2001. He has been the William H. Prusoff Professor and Chairman of the Department of Pharmacology at
Yale School of Medicine The Yale School of Medicine is the graduate medical school at Yale University, a private research university in New Haven, Connecticut. It was founded in 1810 as the Medical Institution of Yale College and formally opened in 1813. The primary te ...
since 2001. He was elected to the
United States National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
in 2000, to the
American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, a ...
in 2001, and to the Institute of Medicine in 2005. He is a member of the editorial boards of several journals, including ''
Cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
'', ''
Molecular Cell ''Molecular Cell'' is a peer-reviewed scientific journal that covers research on cell biology at the molecular level, with an emphasis on new mechanistic insights. It was established in 1997 and is published two times per month. Its 2021 impa ...
'', the ''
Journal of Cell Biology The ''Journal of Cell Biology'' is a peer-reviewed scientific journal published by Rockefeller University Press. History In the early 1950s, a small group of biologists began to explore intracellular anatomy using the emerging technology of ele ...
'', and the ''
Science Science is a systematic endeavor that Scientific method, builds and organizes knowledge in the form of Testability, testable explanations and predictions about the universe. Science may be as old as the human species, and some of the earli ...
'' magazine ''Science Signaling''.


Awards and recognition

Schlessinger is 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 The Dan David Prize is a major international award that recognizes and supports outstanding contributions to the study of history and other disciplines that shed light on the human past. It awards nine prizes of $300,000 each year to outstanding ...
(2006). In 2002, he was granted an
honorary doctorate An honorary degree is an academic degree for which a university (or other degree-awarding institution) has waived all of the usual requirements. It is also known by the Latin phrases ''honoris causa'' ("for the sake of the honour") or ''ad hon ...
from the
University of Haifa The University of Haifa ( he, אוניברסיטת חיפה Arabic: جامعة حيفا) is a university located on Mount Carmel in Haifa, Israel. Founded in 1963, the University of Haifa received full academic accreditation in 1972, becoming ...
. He has lectured 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, he was elected as a Member of the
Croatian Academy of Sciences and Arts The Croatian Academy of Sciences and Arts ( la, Academia Scientiarum et Artium Croatica, hr, Hrvatska akademija znanosti i umjetnosti, abbrev. HAZU) is the national academy of Croatia. HAZU was founded under patronage of the Croatian bishop J ...
. In 2012, the Hope Funds for Cancer Research selected Schlessinger to receive its Award of Excellence for Clinical Development. In 2009, Schlessinger was given an award by then-President of Croatia
Stjepan Mesić Stjepan "Stipe" Mesić (; born 24 December 1934) is a Croatian lawyer and politician who served as President of Croatia from 2000 to 2010. Before serving two five-year terms as president, he was prime minister of SR Croatia (1990) after the fir ...
for outstanding service in promoting Croatia in the international scientific community and for the contribution within Croatian biomedical sciences. In September 2003, ''
The Guardian ''The Guardian'' is a British daily newspaper. It was founded in 1821 as ''The Manchester Guardian'', and changed its name in 1959. Along with its sister papers ''The Observer'' and ''The Guardian Weekly'', ''The Guardian'' is part of the Gu ...
'' listed him as number 14 in the "Giants of Science". He received, along with
Charles Sawyers Charles L. Sawyers (born 1959) is a Howard Hughes Medical Institute (HHMI) investigator who holds the Marie-Josée and Henry R. Kravis Chair of the Human Oncology and Pathogenesis Program (HOPP) at Memorial Sloan Kettering Cancer Center (MSK) ...
and Tony Hunter, the 2014
BBVA Foundation Frontiers of Knowledge Award The BBVA Foundation Frontiers of Knowledge Awards () are an international award programme recognizing significant contributions in the areas of scientific research and cultural creation. The categories that make up the Frontiers of Knowledge Awards ...
in the Biomedicine category for "carving out the path that led to the development of a new class of successful cancer drugs."


Publications and research

According to
PubMed PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain t ...
, Schlessinger has authored over 450 scientific original and review articles in the areas of pharmacology, molecular biology, biochemistry, and structural biology, mostly on
tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...
signaling. Tyrosine kinase signaling plays a critical role in the control of many cellular processes including cell proliferation, differentiation,
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...
, as well as cell survival and
migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
. 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 Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral chemotherapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple receptor tyrosine kin ...
. Among his 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 The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor rece ...
(EGFR). He was also instrumental in understanding how the
SH2 domain The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphor ...
controls tyrosine kinase signaling by binding to phosphorylated tyrosines in activated receptors. One of the seminal findings in this work was his laboratory's cloning of Grb2 and other Adaptor proteins. Another is the lab's cloning of
FRS2 Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the ''FRS2'' gene. FRS2 is an 80 kDa membrane-anchored signal transducing adaptor protein (STAP) that links specific activated Receptor Tyrosine Kinases (RTKs) ...
, which is critical for signaling by the Fibroblast growth factor receptor. In 2001, he was ranked by the ISI Highly Cited as one of the world's top 30 most cited scientists (across all fields) in the 1990s. According to ISI, his papers have been cited a total of 76,699 times.


Controversy

In 2006, a sexual harassment lawsuit was initiated against Yale University by Schlessinger's former secretary, Mary Beth Garceau, who alleged numerous episodes of harassment during her employment at Yale and claimed
Yale University Yale University is a Private university, private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the List of Colonial Colleges, third-oldest institution of higher education in the United Sta ...
failed to act upon her frequent complaints, causing her to resign. The case was settled out of court in mid-2007 and the terms of the settlement were not publicly disclosed.


SUGEN

In 1991, Schlessinger co-founded (with
Axel Ullrich Axel Ullrich (born 19 October 1943) is a German cancer researcher and has been the director of the molecular biology department at the Max Planck Institute of Biochemistry in Martinsried, Germany since 1988. This department's research has primar ...
and Steven Evans-Freke) the biotechnology company
SUGEN SUGEN (Sugen) was a drug discovery company focused on development of protein kinase inhibitors. It was founded in 1991, and shut down in 2003, after pioneering protein kinases as therapeutic targets and developing the successful cancer therapy suni ...
to develop ATP-like molecules that would compete with ATP for binding to the catalytic site of receptor tyrosine kinases in cancer treatment. In 1999, Sugen was acquired by Pharmacia & Upjohn for $650 million and in 2003,
Pharmacia Pharmacia was a pharmaceutical and biotechnological company in Sweden that merged with the American pharmaceutical company Upjohn in 1995. History Pharmacia company was founded in 1911 in Stockholm, Sweden by pharmacist Gustav Felix Grönfeldt ...
was acquired by
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
. One of the pipeline products (SU11248) was ultimately developed by Pfizer as Sutent ( Sunitinib), approved by the FDA for treating gastrointestinal stromal tumors and renal cell carcinoma.


Plexxikon

In 2001, Schlessinger co-founded Plexxikon with Sung-Hou Kim (
University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...
). Plexxikon, uses a pioneering structural biology-based platform for drug discovery. In April 2011, Plexxikon was acquired by the Japanese pharmaceutical company
Daiichi Sankyo is a global pharmaceutical company and the second-largest pharmaceutical company in Japan. It achieved JPY 981.8 billion in revenue in 2019. The company owns the American biotechnology company Plexxikon, American pharmaceutical company American R ...
for $805 million and an additional $130 m in potential milestone payments.


Kolltan Pharmaceuticals

In 2007, Schlessinger co-founded Kolltan Pharmaceuticals with
Arthur Altschul Jr. Arthur is a common male given name of Brythonic origin. Its popularity derives from it being the name of the legendary hero King Arthur. The etymology is disputed. It may derive from the Celtic ''Artos'' meaning “Bear”. Another theory, more wi ...
Kolltan Pharmaceuticals is an early-stage biotech that develops antibodies to treat solid tumors. In April 2014, Kolltan received $60 million in equity financing. In September 2014, Kolltan filed for an
IPO An initial public offering (IPO) or stock launch is a public offering in which shares of a company are sold to institutional investors and usually also to retail (individual) investors. An IPO is typically underwritten by one or more investment ...
and in January 2015, they withdrew the IPO. In November 2016, Celldex Therapeutics acquired Kolltan for $235 million.Genetic Engineering and Biotechnology News: "Celldex to Acquire Kolltan for Up to $235M"
2 November 2016


References


External links

*
Yale School of Medicine appoints Joseph Schlessinger, formerly of NYU, Pharmacology Chair.
{{DEFAULTSORT:Schlessinger, Joseph 1945 births People from Topusko Living people Croatian Jews Croatian atheists American biochemists Israeli biochemists Jewish chemists Jewish American atheists Yale School of Medicine faculty Members of the United States National Academy of Sciences Foreign Members of the Russian Academy of Sciences Croatian emigrants to Israel Yugoslav emigrants to Israel Israeli atheists Israeli people of Croatian-Jewish descent Members of the National Academy of Medicine