Sims / Wiedmer Lab Peter J. Sims, M.D., Ph.D. View Dr. Sims' profile M.D. 1980 Duke University School of Medicine Ph.D. 1980 Duke University School of Medicine Professor, Department of Pathology and Laboratory Medicine Therese Wiedmer, Ph.D. View Dr. Wiedmer's profile Ph.D. 1977 Switzerland - University of Bern Associate Professor, Department of Pathology and Laboratory Medicine Research Overview The Sims/Wiedmer Laboratory originally discovered and cloned phospholipid scramblase as a membrane protein with capacity to promote rapid transbilayer movement of phospholipids in response to Ca2+. This protein turned out to be the first of four that together form the phospholipid scramblase (PLSCR) gene family. The lab’s research during the last few years has revealed that PLSCRs may have functions beyond their putative role as membrane phospholipid scramblases. Taking advantage of gene knockout technology, we discovered that mice with a targeted deletion of PLSCR1 display perinatal granulocytopenia due to defective response to (should this be “of”?) hematologic precursors to granulocyte colony-stimulating factor and stem cell factor. Interestingly, PLSCR3-/- mice have a phenotype reminiscent of metabolic syndrome in man: they display aberrant accumulation of abdominal fat, accompanied by the development of insulin resistance, glucose intolerance and dyslipidemia. These observations and our in vitro data suggest that PLSCRs are involved in signal transduction through growth factor receptors and may be required for normal cell maturation. Furthermore, we have shown that aberrant expression of PLSCR1 may play a role in tumor formation and increased susceptibility to viral infection. Current efforts are focused on unraveling the molecular mechanisms by which PLSCRs mediate these diverse functions.