Joseph Goldstein, M.D.

Joseph L. Goldstein is currently Chairman of the Department of Molecular Genetics at UT Southwestern Medical Center. In 1985, he was named Regental Professor of the University of Texas. He also holds the Paul J. Thomas Chair in Medicine and the Julie and Louis A. Beecherl Distinguished Chair in Biomedical Science. Dr. Goldstein and his colleague, Michael S. Brown, discovered the low density lipoprotein (LDL) receptor and worked out how these receptors control cholesterol homeostasis. At the basic level, this work opened the field of receptor-mediated endocytosis, and at the clinical level it helped lay the conceptual groundwork for development of drugs called statins that lower blood LDL-cholesterol and prevent heart attacks.

Drs. Goldstein and Brown shared many awards for this work, including the Lasker Award in Basic Medical Research (1985), Nobel Prize in Physiology or Medicine (1985), and National Medal of Science (1988). In recent work, Drs. Goldstein and Brown discovered the SREBP family of transcription factors and showed how these membrane-bound molecules control the synthesis of cholesterol and fatty acids through a newly described process of Regulated Intramembrane Proteolysis. For this work, Drs. Brown and Goldstein received the Albany Medical Center Prize in Medicine and Biomedical Research (2003). Dr. Goldstein is currently 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 also serves on the Scientific Advisory Boards of the Welch Foundation, Memorial Sloan-Kettering Cancer Center, Scripps Research Institute, Van Andel Institute, and the Massachusetts General Hospital. He is a member of the US National Academy of Sciences and a Foreign Member of the Royal Society.

 

Undergraduate	Washington and Lee University (1962)
Medical School	University of Texas Southwestern Med Ctr Dallas (1966)

• Cholesterol and Lipoprotein Metabolism
• Genetics of Human Disease

Featured Publications

Protein sensors for membrane sterols.

Goldstein, J.L., DeBose-Boyd, R.A. and Brown, M.S. Cell 2006 124 35-46

Direct binding of cholesterol to the purified membrane region of SCAP: Mechanism for a sterol-sensing domain.

Radhakrishnan, A., Sun, L.-P., Kwon, H.J., Brown, M.S., and Goldstein, J.L. Molecular Cell 2004 15 259-268

Crucial step in cholesterol homeostasis: Sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in the ER.

Yang, T., Espenshade, P.J., Wright, M.E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J.L., and Brown, M.S. Cell 2002 110 489-500

Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.

Shimomura, I., Hammer, R.E., Ikemoto, S., Brown, M.S., and Goldstein, J.L. Nature 1999 401 73-76

The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor.

Brown, M.S. and Goldstein, J.L. Cell 1997 89 331-340

Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis.

Li, S., Brown, M.S. and Goldstein, J.L. Proc. Natl. Acad. Sci. USA 2010 107 3441-3446

Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice.

Zhao, T.-J., Liang, G., Li, R.L., Xie, X., Sleeman, M.W., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Goldstein, J.L., and Brown, M.S. Proc. Natl. Acad. Sci. USA 2010 107 7467-7472

Identification of surface residues on Niemann-Pick C2 (NPC2) essential for hydrophobic handoff of cholesterol to NPC1 in lysosomes.

Wang, M.L., Motamed, M., Infante, R.E., Abi-Moshel, L., Kwon, H.J., Brown, M.S. and Goldstein, J.L. Cell Metab. 2010 12 166-173

HDL miR-d down by SREBP introns.

Brown, M.S., Ye, J., and Goldstein, J.L. Science 2010 328 1495-1496

Ghrelin secretion stimulated by Beta1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.

Zhao, T.-J., Sakata, I., Li, R.L., Liang, G., Richardson, J.A., Brown, M.S., Goldstein, J.L., and Zigman, J.M. Proc. Natl. Acad. Sci. USA 2010 107 15868-15873

• Albany Medical Center Prize in Biomedical Research
  (2003)
• Warren Alpert Foundation Prize
  (2000)
• U.S. National Medal of Science
  (1988)
• Albert D. Lasker Award in Basic Medical Research
  (1985)
• Nobel Prize In Physiology or Medicine
  (1985)

• American Philosophical Society
• Association of American Physicians
• Institute of Medicine
• Royal Society (London)
• U.S. National Academy of Sciences