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

Professor of Pathology and Laboratory Medicine

The biological function of phospholipid scramblases (PLSCRs)

URMC Labs
601 Elmwood Ave., Rm G-2105
Rochester, NY 14642-8626
Tel: (585) 276-3007
Fax: (585) 276-2272

Peter_Sims@urmc.rochester.edu

Qualifications

M.D. Duke University School of Medicine 1980
Ph.D., Physiology and Pharmacology, Duke University School of Medicine 1980
Resident in Pathology, University of Virginia Hospital 1980-82
Fellow in Pathology, University of Virginia Hospital 1982-83

Professional Activities

President, American Heart Association Oklahoma Affiliate 1991-92
Chairman, Veterans Administration Merit Review Board (Hematology) 1991-92
Zyma Foundation Visiting Professor, Institue of Biochemistry, University of Lausanne 1992
Walter H. Schroeder Chair in Research, The Blood Center of Southeastern Wisconsin, 1993-99
NIH (NHLBI) MERIT Award 1995
Chairman, NIH Hematology 1 Study Section 1999-2001
Adjunct Professor, Shanghai Second Medical University, China 2004-present

Research Overview

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. See also Faculty page of collaborating investigator Dr. Therese Wiedmer.

Publications

Li Y, Rogulski K, Zhou Q, Sims PJ, Prochownik EV (2006). The negative c-Myc target onzin affects proliferation and apoptosis via interaction with phospholipid scramblase 1. Mol. Cell. Biol. 3401-3413

Zhao K-W, Li D, Zhao Q, Huang Y, Silverman RH, Sims PJ, Chen G-Q (2005). Interferon-a induced expression of phospholipid scramblase 1 through STAT1 requires the sequential activation of protein kinase Cd & JNK. J. Biol. Chem. 280: 42707 – 42714

Zhou Q, Ben-Efraim I, Bigcas J-L, Wiedmer T, and Sims PJ (2005). Phospholipid scramblase 1 binds to the promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene to enhance its expression. J. Biol. Chem. 280: 35062-35068

Chen M-H, Ben-Efraim I, Mitrousis G, Walker-Kopp N, Sims PJ, and Cingolani G (2005). Phospholipid scramblase 1 (PLSCR1) contains a non-classical nuclear localization signal with unique binding site in importin alpha. J. Biol. Chem. 280: 10599-10606

Wiedmer T, Zhao J, Li L, Zhou Q, Hevener A, Olefsky JM, Curtiss LK, and Sims PJ (2004). Adiposity, dyslipidemia, and insulin resistance in mice with targeted deletion of phospholipid scramblase 3. Proceed. Natl. Acad Sci. USA. 101:13296-13301

Dong B, Zhou Q, Zhao J, Zhou A, Harty RN, Bose S, Banerjee A, Slee R, Guenther J, Williams BRG, Wiedmer T, Sims PJ, and Silverman RH.(2004) Phospholipid scramblase 1 potentiates the antiviral activity of interferon. J. Virology. 78: 8983-8993

Ben-Efraim I, Zhou Q, Wiedmer T, Gerace L, and Sims PJ (2004). Phospholipid scramblase 1 (PLSCR1) is imported into the nucleus by a receptor-mediated pathway and interacts with DNA. Biochemistry . 43: 3518-3526

Nanjundan M, Sun J, Zhao J, Zhou Q, Sims PJ, and Wiedmer T (2003). Plasma membrane phospholipid scramblase 1 promotes EGF-dependent activation of c-Src through the epidermal growth factor receptor. J. Biol. Chem. 278: 37413-37418

Wiedmer T, Zhao J, Nanjundan M, and Sims PJ (2003) Palmitoylation of phospholipid scramblase 1 (PLSCR1) controls its distribution between nucleus and plasma membrane. Biochemistry. 42: 1227-1233

Zhou Q, Zhao J, Wiedmer T, and Sims PJ (2002). Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1. Blood. 99: 4030-4038

Silverman RH, Halloum A, Zhou A, Dong B, Al-Zoghaibi F, Kushner D, Zhou Q, Zhao J, Wiedmer T and Sims PJ (2002). Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1. Cancer Research. 62: 397-402

Sun J, Zhao J, Schwartz MA, Wang JYJ, Wiedmer T, Sims PJ (2001). c-Abl tyrosine kinase binds and phosphorylates phospholipid scramblase 1. J. Biol. Chem. 276:28984-28990

Zhou Q, Zhao J, Al-Zoghaibi F, Zhou A, Wiedmer T, Silverman RH, Sims PJ. (2000). Transcriptional control of the human plasma membrane phospholipid scramblase 1 gene is meditated by interferon alpha. Blood. 95: 2593-2599

Zhou Q, Zhao J, Stout JG, Luhm RA, Wiedmer T, Sims PJ (1997). Molecular cloning of human plasma membrane phospholipid scramblase: a protein mediating transbilayer movement of plasma membrane phospholipids. J. Biol. Chem. 272(29):18240-18244

Bassé F, Stout JG, Sims PJ, and Wiedmer T (1996). Isolation of an erythrocyte membrane protein that mediates Ca2+- dependent transbilayer movement of phospholipid. J. Biol. Chem. 271:17205-17210

All PubMed Publications for Sims PJ