Peter J. Sims, M.D., Ph.D.

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We 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. Our 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 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.

Current Appointments

• Professor - Department of Pathology and Laboratory Medicine (SMD)

Education
MD Medicine	Duke University Sch Medicine	1980
PhD Pharmacology	Duke University Sch Medicine	1980
BA Biophysics	Amherst College	1974

Board Certifications
Diplomate of National Board of Medical Examiners

Lab Description

Regulation of immune and thrombo-embolic events by phospholipids and other components of the plasma membrane; structure and function of the phospholipid scramblase gene family.

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Recent Journal Articles
Showing the 5 most recent journal articles. (120 available)
Bateman A; Finn RD; Sims PJ; Wiedmer T; Biegert A; Söding J. "Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors." Bioinformatics (Oxford, England). 2009; 25(2):159-62. Epub 2008 Nov 13.
Mutch DM; O'Maille G; Wikoff WR; Wiedmer T; Sims PJ; Siuzdak G. "Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice." Genome biology. 2007; 8(3):R38.
Lu B; Sims PJ; Wiedmer T; Moser AH; Shigenaga JK; Grunfeld C; Feingold KR. "Expression of the phospholipid scramblase (PLSCR) gene family during the acute phase response." Biochimica et biophysica acta. 2007; 1771(9):1177-85. Epub 2007 May 26.
Li Y; Rogulski K; Zhou Q; Sims PJ; Prochownik EV. "The negative c-Myc target onzin affects proliferation and apoptosis via its obligate interaction with phospholipid scramblase 1." Molecular and cellular biology. 2006; 26(9):3401-13.
Huang Y; Zhao Q; Zhou CX; Gu ZM; Li D; Xu HZ; Wiedmer T; Sims PJ; Zhao KW; Chen GQ. "Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cells." Oncogene. 2006; 25(50):6618-27. Epub 2006 May 15.