Brown and Goldstein (U Texas Southwestern): Molecular Basis of Familial Hypercholesterolemia

Joseph Goldstein and Michael Brown describe how studying familial hypercholesterolemia led to the discovery of LDL receptors and receptor-mediated endocytosis.

ibiology.org/cell-biology/familial-hypercholesterolemia/ While post-doctoral fellows at the NIH, Joe Goldstein and Michael Brown were presented with a young patient with familial hypocholesterolemia (FH), a disease characterized by high LDL cholesterol and atherosclerosis. Scientific curiosity along with a desire to help these patients led Brown and Goldstein to dedicate themselves to understand the biological basis for FH. In their first talk, Brown and Goldstein describe the excitement of discovering that cells from an FH patient could not take up LDL cholesterol, which then led to the discovery of LDL receptors and the mechanism of receptor-mediated endocytosis. Biographies Joseph Goldstein is Chair of the Department of Molecular Genetics at the University of Texas Southwestern Medical Center and Michael Brown is Professor of Molecular Genetics and Director of the Jonsson Center for Molecular Genetics at UTSW. For over 40 years, Drs. Brown and Goldstein have directed a lab together and worked to understand the genetics and regulation of cholesterol metabolism. Together, they discovered that a defect in the uptake of LDL is a major cause of the human disease familial hypercholesterolemia. This work led to the discovery of the LDL receptor, receptor-mediated endocytosis, and mechanisms for regulating cholesterol synthesis and provided the foundation for the development of statins, drugs taken by millions to control elevated cholesterol levels. Their research has been recognized with the Albert Lasker Basic Medical Research Award, the Nobel Prize in Physiology or Medicine, and the National Medal of Science. Currently, Brown and Goldstein’s research focuses on the SREBP family of transcription factors and their role in regulating lipid metabolism.