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Joseph Schlessinger (born Josip Schlessinger; 26 March 1945) is a Yugoslav-born Israeli- American
biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...
and biophysician. He is chair of the
Pharmacology Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...
Department at
Yale University Yale University is a Private university, private Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the List of Colonial Colleges, third-oldest institution of higher education in the United Stat ...
School of Medicine in
New Haven New Haven is a city of the U.S. state of Connecticut. It is located on New Haven Harbor on the northern shore of Long Island Sound. With a population of 135,081 as determined by the 2020 U.S. census, New Haven is the third largest city in Co ...
, 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 conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...
, 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 Municipalities of Croatia, municipality and settlement in Sisak-Moslavina County, Croatia. Topusko is an underdeveloped municipality which is statistically classified as the Areas of Special State Concern (Croatia), First Category Are ...
to Jewish parents. His father Imre came from Szalatnok,
Kingdom of Hungary The Kingdom of Hungary was a monarchy in Central Europe that existed for nearly a millennium, from 1000 to 1946 and was a key part of the Habsburg monarchy from 1526-1918. The Principality of Hungary emerged as a Christian kingdom upon the Coro ...
,
Kingdom of Hungary The Kingdom of Hungary was a monarchy in Central Europe that existed for nearly a millennium, from 1000 to 1946 and was a key part of the Habsburg monarchy from 1526-1918. The Principality of Hungary emerged as a Christian kingdom upon the Coro ...
, since 1920 Slatina; Imre's first wife and child had been deported to
Auschwitz Auschwitz, or Oświęcim, was a complex of over 40 concentration and extermination camps operated by Nazi Germany in occupied Poland (in a portion annexed into Germany in 1939) during World War II and the Holocaust. It consisted of Auschw ...
. Schlessinger's mother Rivka was from
Bugojno Bugojno ( sr-cyrl, Бугојно) is a town and municipality in the Central Bosnia Canton of the Federation of Bosnia and Herzegovina, an entity of Bosnia and Herzegovina. It is situated on the river Vrbas, to the northwest of Sarajevo. Accord ...
; her first husband had been murdered by the
Ustaše The Ustaše (), also known by anglicised versions Ustasha or Ustashe, was a Croats, Croatian fascist and ultranationalist organization active, as one organization, between 1929 and 1945, formally known as the Ustaša – Croatian Revolutionar ...
. Imre and Rivka met in a labor camp on the Adriatic island of Rab in 1943 and joined a group of Jewish Partisans. When Schlessinger was born on 26 March 1945 he was wrapped in a
British military The British Armed Forces are the unified military forces responsible for the defence of the United Kingdom, its Overseas Territories and the Crown Dependencies. They also promote the UK's wider interests, support international peacekeeping e ...
parachute. He was named for his grandfather. After World War II the family moved to
Osijek Osijek () is the fourth-largest city in Croatia, with a population of 96,848 in 2021. It is the largest city and the economic and cultural centre of the eastern Croatian region of Slavonia, as well as the administrative centre of Osijek-Baranja ...
, where another son, Darko David, was born. Imre Schlessinger once made a joke at the expense of Tito 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 The 1st "Golani" Brigade (, ''Hativat Golani'') is an Israeli military infantry brigade. It is subordinated to the 36th Division and traditionally associated with the Northern Command. It is one of the five infantry brigades of the regular Is ...
and was commissioned an officer. As part of his reserve duty he participated in the
Six-Day War The Six-Day War, also known as the June War, 1967 Arab–Israeli War or Third Arab–Israeli War, was fought between Israel and a coalition of Arab world, Arab states, primarily United Arab Republic, Egypt, Syria, and Jordan from 5 to 10June ...
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 fought from 6 to 25 October 1973 between Israel and a coalition of Arab world, Arab states led by Egypt and S ...
. Schlessinger received his BSc degree in
Chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...
and
Physics Physics is the scientific study of matter, its Elementary particle, 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 whi ...
in 1968 (magna cum laude), and an MSc degree in chemistry (also magna cum laude) in 1970 from the
Hebrew University of Jerusalem The Hebrew University of Jerusalem (HUJI; ) is an Israeli public university, public research university based in Jerusalem. Co-founded by Albert Einstein and Chaim Weizmann in July 1918, the public university officially opened on 1 April 1925. ...
. 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 ( ''Machon Weizmann LeMada'') is a Public university, public research university in Rehovot, Israel, established in 1934, fourteen years before the State of Israel was founded. Unlike other List of Israeli uni ...
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 university, private Ivy League research university based in Ithaca, New York, United States. The university was co-founded by American philanthropist Ezra Cornell and historian and educator Andrew Dickson W ...
in
Ithaca, New York Ithaca () is a city in and the county seat of Tompkins County, New York, United States. Situated on the southern shore of Cayuga Lake in the Finger Lakes region of New York (state), New York, Ithaca is the largest community in the Ithaca metrop ...
, 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, also a 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 () is a Croatian daily newspaper based in Zagreb. It was published on 6 April 1998 by EPH (Europapress holding, owned by Ninoslav Pavić), which eventually changed its name in Hanza Media after being bought by Marijan Hanžeković. The newspap ...
'', 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 biology and medicine that covers the study of Immune system, immune systems in all Organism, organisms. Immunology charts, measures, and contextualizes the Physiology, physiological functioning of the immune system in ...
from 1985 to 1991. In addition, he was a research director for Rorer Biotechnology in
King of Prussia, Pennsylvania King of Prussia (nicknamed K.O.P.) is a census-designated place in Upper Merion Township, Pennsylvania, Upper Merion Township in Montgomery County, Pennsylvania, United States. The community took its unusual name in the 18th century from a loca ...
, from 1985 to 1990. In 1990, he was appointed as the Milton and Helen Kimmelman Professor and chairman of the department of
pharmacology Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...
at the
New York University School of Medicine The New York University 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, the other being the NYU G ...
. 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 Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...
at
Yale School of Medicine The Yale School of Medicine is the medical school of 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. It is the sixth-oldest m ...
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 (The Academy) 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, and other ...
in 2001, and to the
Institute of Medicine The National Academy of Medicine (NAM), known as the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Engineerin ...
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 * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
'', '' Molecular Cell'', 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 e ...
'', and the ''
Science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...
'' 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 an international group of awards that recognize and support outstanding contributions to the study of history and other disciplines that shed light on the human past. Nine prizes of $300,000 are awarded each year to outstand ...
(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 (, ) is a public research university located on Mount Carmel in Haifa, Israel. Founded in 1963 as a branch of the Hebrew University of Jerusalem, the University of Haifa received full academic accreditation as an inde ...
. 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 (; , HAZU) is the national academy of Croatia. HAZU was founded under the patronage of the Croatian bishop Josip Juraj Strossmayer under the name Yugoslav Academy of Sciences and Arts (, JAZU) since its ...
. 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 Croatia, Croatian lawyer and politician who served as the president of Croatia from 2000 to 2010. Before serving two five-year terms as president, he was Prime Minister of Croatia, prime minis ...
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 Manchester in 1821 as ''The Manchester Guardian'' and changed its name in 1959, followed by a move to London. Along with its sister paper, ''The Guardian Weekly'', ''The Guardi ...
'' listed him as number 14 in the "Giants of Science". He received, along with Charles Sawyers 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 an openly accessible, free database which includes 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 Institute ...
, 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 Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...
, differentiation,
metabolism Metabolism (, from ''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 cellular processes; the co ...
, 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 Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases ...
or Gleevec. 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 (biochemistry), receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligand (biochemistry ...
(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 bind to phosphorylated tyrosine residues on other proteins, ...
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 Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/ cell communication. In humans, the GRB2 protein is encoded by the ''GRB2'' gene. The protein encoded by this gene binds recepto ...
and other Adaptor proteins. Another is the lab's cloning of FRS2, which is critical for signaling by the
Fibroblast growth factor receptor The fibroblast growth factor receptors (FGFR) are, as their name implies, receptors that bind to members of the fibroblast growth factor (FGF) family of proteins. Some of these receptors are involved in pathological conditions. For example, a po ...
. In 2001, he was ranked by the
ISI Highly Cited The Institute for Scientific Information (ISI) was an academic publishing service, founded by Eugene Garfield in Philadelphia in 1956. ISI offered scientometric and bibliographic database services. Its specialty was citation indexing and analysis ...
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.


Select publications

* * *


Controversy

In 2006, a
sexual harassment Sexual harassment is a type of harassment based on the sex or gender of a victim. It can involve offensive sexist or sexual behavior, verbal or physical actions, up to bribery, coercion, and assault. Harassment may be explicit or implicit, wit ...
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 Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the List of Colonial Colleges, third-oldest institution of higher education in the United Stat ...
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 pri ...
and Steven Evans-Freke) the biotechnology company SUGEN 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 Grönfel ...
was acquired by
Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...
. One of the pipeline products (SU11248) was ultimately developed by Pfizer as Sutent (
Sunitinib Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imat ...
), 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 university, public Land-grant university, land-grant research university in Berkeley, California, United States. Founded in 1868 and named after t ...
). 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 1,278 billion in revenue in 2022. The company owns the American pharmaceutical company American Regent. Daiichi Sankyo, Inc. (DSI) began ...
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. 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 American atheists American biochemists Croatian Jews Croatian atheists 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