Joseph L. Goldstein
Encyclopedia
Joseph L. Goldstein from Kingstree, South Carolina
is a Nobel Prize
winning biochemist
and geneticist
, and a pioneer in the study of cholesterol metabolism.
in 1962 and his M.D. from the University of Texas Southwestern Medical Center
in 1966. In 1985 he received the Nobel Prize in Physiology or Medicine
(together with Michael S. Brown) for his research on the metabolism of low density lipoprotein
(LDL), and has won numerous other awards for his contributions related to genetic disease
s.
Returning to the University of Texas Health Science Center in Dallas in 1972 (now called UT Southwestern Medical Center) Goldstein and his close colleague Brown researched cholesterol metabolism and discovered that human cells have low-density lipoprotein (LDL) receptors that extract cholesterol from the bloodstream. The lack of sufficient LDL receptors is the cause of familial hypercholesterolemia
, which predisposes heavily for cholesterol-related diseases. In addition to explaining the underlying pathology of the widely-observed link between high levels of circulating cholesterol
as LDL and coronary artery disease, their work uncovered a previously-unappreciated fundamental aspect of cell biology - Receptor-mediated endocytosis
.
Goldstein and Brown's findings led to better understanding the mechanism of action of statin
drugs, the cholesterol-lowering compounds that today are used by 16 million Americans and are the most widely prescribed medications in the United States. New federal cholesterol guidelines are expected to triple the number of Americans taking statin drugs to lower their cholesterol, reducing the risk of heart disease and stroke for countless people. Subsequently the team led by Drs. Brown and Goldstein elucidated the role of lipid modification of proteins (protein prenylation
) in cancer
.
In 1993, their postdoctoral trainees Wang Xiaodong
and Michael Briggs purified the Sterol Regulatory Element-Binding Proteins (SREBPs
), a family of membrane-bound transcription factors. Since 1993, Drs. Goldstein, Brown, and their colleagues have described the unexpectedly complex machinery
that proteolytically releases the SREBPs from membranes, thus allowing their migration to the nucleus where they activate all the genes involved in the synthesis of cholesterol and fatty acids. The machinery for generating active SREBPs is tightly regulated by a negative feedback mechanism, which explains how cells maintain the necessary levels of fats and cholesterol in the face of varying environmental circumstances.
Goldstein is a Regental Professor of the University of Texas Southwestern Medical Center at Dallas
, holds the Julie and Louis A. Beecherl Distinguished Chair in Biomedical Science, and the Paul J. Thomas Chair in Medicine. Frequently mentioned as a candidate for nationally-prominent positions in scientific administration, Goldstein, like his colleague Michael S. Brown, elects to continue hands-on involvement with research. Together, they lead a research team that typically includes a dozen doctoral and postdoctoral trainees. He and his colleague are among the most highly cited scientists in the world.
Goldstein currently serves as Chairman of the Albert Lasker Medical Research Awards Jury
and is a member of the Boards of Trustees of the Howard Hughes Medical Institute
and The Rockefeller University. He is also a member of the U.S. National Academy of Sciences and a Foreign Member of The Royal Society.
Kingstree, South Carolina
Kingstree is a town in and the county seat of Williamsburg County, South Carolina, United States. The population was 3,328 at the 2010 census.-History:...
is a Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
winning biochemist
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
and geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
, and a pioneer in the study of cholesterol metabolism.
Biography
Dr. Goldstein received a BS in chemistry from Washington and Lee UniversityWashington and Lee University
Washington and Lee University is a private liberal arts college in Lexington, Virginia, United States.The classical school from which Washington and Lee descended was established in 1749 as Augusta Academy, about north of its present location. In 1776 it was renamed Liberty Hall in a burst of...
in 1962 and his M.D. from the University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
The University of Texas Southwestern Medical Center is one of the biomedical research institutions of the University of Texas System, incorporating three degree-granting institutions, four affiliated hospitals, including Parkland Memorial, the teaching hospital, and biomedical research...
in 1966. In 1985 he received the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
(together with Michael S. Brown) for his research on the metabolism of low density lipoprotein
Low density lipoprotein
Low-density lipoprotein is one of the five major groups of lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, that enable transport of cholesterol within the water-based bloodstream...
(LDL), and has won numerous other awards for his contributions related to genetic disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
s.
Returning to the University of Texas Health Science Center in Dallas in 1972 (now called UT Southwestern Medical Center) Goldstein and his close colleague Brown researched cholesterol metabolism and discovered that human cells have low-density lipoprotein (LDL) receptors that extract cholesterol from the bloodstream. The lack of sufficient LDL receptors is the cause of familial hypercholesterolemia
Familial hypercholesterolemia
Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein , in the blood and early cardiovascular disease...
, which predisposes heavily for cholesterol-related diseases. In addition to explaining the underlying pathology of the widely-observed link between high levels of circulating cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
as LDL and coronary artery disease, their work uncovered a previously-unappreciated fundamental aspect of cell biology - Receptor-mediated endocytosis
Receptor-mediated endocytosis
Receptor-mediated endocytosis , also called clathrin-dependent endocytosis, is a process by which cells internalize molecules by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.-Process:After the binding of a...
.
Goldstein and Brown's findings led to better understanding the mechanism of action of statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
drugs, the cholesterol-lowering compounds that today are used by 16 million Americans and are the most widely prescribed medications in the United States. New federal cholesterol guidelines are expected to triple the number of Americans taking statin drugs to lower their cholesterol, reducing the risk of heart disease and stroke for countless people. Subsequently the team led by Drs. Brown and Goldstein elucidated the role of lipid modification of proteins (protein prenylation
Prenylation
Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...
) in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
In 1993, their postdoctoral trainees Wang Xiaodong
Wang Xiaodong
Xiaodong Wang is an American biochemist best known for his work with cytochrome c. His laboratory developed an in-vitro assay for the activation of the apoptosis related proteinase Caspase-3. This allowed the biochemical purification a complex of Cytochrome c, Caspase-9 and the Apoptotic Protease...
and Michael Briggs purified the Sterol Regulatory Element-Binding Proteins (SREBPs
Sterol regulatory element binding protein
Sterol Regulatory Element-Binding Proteins are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors...
), a family of membrane-bound transcription factors. Since 1993, Drs. Goldstein, Brown, and their colleagues have described the unexpectedly complex machinery
Sterol regulatory element binding protein
Sterol Regulatory Element-Binding Proteins are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors...
that proteolytically releases the SREBPs from membranes, thus allowing their migration to the nucleus where they activate all the genes involved in the synthesis of cholesterol and fatty acids. The machinery for generating active SREBPs is tightly regulated by a negative feedback mechanism, which explains how cells maintain the necessary levels of fats and cholesterol in the face of varying environmental circumstances.
Goldstein is a Regental Professor of the University of Texas Southwestern Medical Center at Dallas
University of Texas Southwestern Medical Center at Dallas
The University of Texas Southwestern Medical Center is one of the biomedical research institutions of the University of Texas System, incorporating three degree-granting institutions, four affiliated hospitals, including Parkland Memorial, the teaching hospital, and biomedical research...
, holds the Julie and Louis A. Beecherl Distinguished Chair in Biomedical Science, and the Paul J. Thomas Chair in Medicine. Frequently mentioned as a candidate for nationally-prominent positions in scientific administration, Goldstein, like his colleague Michael S. Brown, elects to continue hands-on involvement with research. Together, they lead a research team that typically includes a dozen doctoral and postdoctoral trainees. He and his colleague are among the most highly cited scientists in the world.
Goldstein currently serves as Chairman of the Albert Lasker Medical Research Awards Jury
Lasker Award
The Lasker Awards have been awarded annually since 1946 to living persons who have made major contributions to medical science or who have performed public service on behalf of medicine. They are administered by the Lasker Foundation, founded by advertising pioneer Albert Lasker and his wife Mary...
and is a member of the Boards of Trustees of the Howard Hughes Medical Institute
Howard Hughes Medical Institute
Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...
and The Rockefeller University. He is also a member of the U.S. National Academy of Sciences and a Foreign Member of The Royal Society.
Awards
- In 1981, Goldstein was awarded the Gairdner Foundation International Award together with Michael S. Brown (Co-winner of 1985 Nobel Prize in Physiology or MedicineNobel Prize in Physiology or MedicineThe Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
).
- In 1984, he was awarded the Louisa Gross Horwitz PrizeLouisa Gross Horwitz PrizeLouisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers that have made an outstanding contribution in basic research in the fields of biology or biochemistry....
from Columbia UniversityColumbia UniversityColumbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
(shared with Michael S. Brown).
- In 1985, he received the Albert D. Lasker Award in Basic Medical ResearchLasker AwardThe Lasker Awards have been awarded annually since 1946 to living persons who have made major contributions to medical science or who have performed public service on behalf of medicine. They are administered by the Lasker Foundation, founded by advertising pioneer Albert Lasker and his wife Mary...
(shared with Michael S. Brown).
- In 1988, he received the National Medal of ScienceNational Medal of ScienceThe National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social sciences, biology, chemistry, engineering, mathematics and...
.
- In 2003, he was awarded the Albany Medical Center PrizeAlbany Medical Center PrizeThe is the United States' highest value prize in medicine and biomedical research. Among prizes for medicine, the Albany Medical Center Prize is second only to the $1.4 million Nobel Prize in Medicine and the $1 million Shaw Price in life science and medicine....
(shared with Michael S. Brown).