Affiliations

Distinguished Professor, Medicine

Professor, Human Genetics

Member, Biochemistry, Biophysics & Structural Biology GPB Home Area, Genetics & Genomics GPB Home Area, Molecular, Cellular & Integrative Physiology GPB Home Area

Faculty, Cardiology

We identified a GPI-anchored endothelial cell protein, GPIHBP1, that is required for the processing of triglyceride-rich lipoproteins (TRLs). We went on to show that GPIHBP1 binds lipoprotein lipase (LPL) in the interstitial spaces and shuttles it across endothelial cells to its site of action in the capillary lumen. In the absence of GPIHBP1, LPL remains mislocalized in the interstitial spaces and never reaches the capillary lumen. The mislocalization of LPL severely impairs the processing of TRLs in the plasma, causing severe hypertriglyceridemia. We have identified many GPIHBP1 mutations causing hypertriglyceridemia in humans; all of those interfere with the binding of LPL. Currently, we are working on mechanisms by which the fatty acid products of TRL processing move across capillary endothelial cells to vital tissues such as the heart. We also study the role of the nuclear lamin proteins in health and disease. Nuclear lamins are building blocks for the nuclear lamina, a structural scaffolding for the cell nucleus. Over the past few years, we elucidated the in vivo importance of the B-type lamins, lamin B1 and lamin B2, two key proteins of the nuclear lamina. We showed that both lamin B1 and lamin B2 are essential for the migration of neurons in the developing brain. We have also worked to develop strategies for treating genetic diseases caused by defective biogenesis of lamin A, another protein of the nuclear lamina.

Stephen Young grew up in Kansas and obtained an undergraduate degree in history from Princeton University. Following medical school at Washington University-St. Louis, he did internal medicine training at UCSF and cardiology training at UCSD. He then embarked on a career in basic science. He did postdoctoral research training in lipid metabolism at UCSD with Dr. Joseph Witztum and then worked at a UCSF-affiliated research institute for 17 years. Along the way, he became an expert in using genetically modified mice to investigate the gene function in health and disease. Currently, his laboratory studies an endothelial cell protein required for plasma triglyceride metabolism and diseases of the nuclear envelope. His laboratory has a strong track record in developing the careers of young scientists. Dr. Young has received multiple awards and is a member of the National Academy of Sciences.

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