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Therese Wiedmer, Ph.D.

Associate Professor of Pathology and Laboratory Medicine

Role of phospholipid scramblases (PLSCRs)
in cell response to growth factors

URMC Labs
601 Elmwood Ave., Rm G-2117
Rochester, NY 14642-8626
Tel: (585) 276-3009
Fax: (585) 276-2272

Therese_Wiedmer@urmc.rochester.edu

Co-Director of Pathways of Human Disease graduate program in Pathology

Qualifications

Ph.D., Biochemistry, University of Bern, Switzerland 1977
Postdoctoral Fellow, Physiology, Duke University Medical Center 1979-80

Professional Activities

Member, Hematology I Study Section, NIH-NHLBI 1991-95
Member, NIH Reviewers Reserve 1995 - present

Adjunct Professor, Soochow University Suzhou, China 2009-present

Research Overview

Our laboratory is focusing on a family of proteins called phospholipid scramblases. We originally cloned phospholipid scramblase 1 (PLSCR1), a Ca2+-binding, endofacial plasma membrane protein, based on its capacity to promote rapid transbilayer movement of phospholipids in response to elevated Ca2+. Such redistribution of phospholipids is normally observed upon platelet activation, and in injured or apoptotic cells. We subsequently identified three additional members of this gene family. Recent data from our laboratory suggest a considerably more complex biology for this protein than its putative role in mediating transbilayer lipid movement. We have accumulated evidence that PLSCR1 -- and possibly other members of the PLSCR gene family -- plays a role in modulating the signaling through multiple growth factor receptors, and have shown that PLSCR1 is itself transcriptionally upregulated through these same growth factor receptor pathways. We also recently discovered that when transcriptionally induced, a portion of the newly synthesized PLSCR1 translocates to the nucleus, in addition to its usual location at the plasma membrane, where it can increase gene transcription. One such gene identified to be upregulated in presence of PLSCR1 is the IP3-receptor type 1. Our current efforts are aimed at elucidating the role of PLSCRs in diverse signaling pathways underlying proliferation, differentiation, and apoptosis. See also Faculty page of collaborating investigator Dr. Peter J. Sims .

Publications

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. 2009 Jan; 25(2):159-162.

Mutch, DM, O’Maille G, Wikoff W, 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. Biochim Biophys Acta. 2007 Sept;1771(9):1177–1185.

Huang Y, Zhao Q, Zhou C-X, Gu Z-M, Li D, Xu H-Z, Wiedmer T, Sims PJ, Zhao K-W, Chen G-Q . Anti-leukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cells. Oncogene. 2006 Oct;25(50):6618-6627.

Zhou Q, Ben-Efraim, I, Bigcas JL, Junqueira, D, Wiedmer T, 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

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 (PLSCR3). Proc. 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

Zhao KW, Li X, Zhao Q, Huang Y, Li D, Peng ZG, Shen WZ, Zhao J, Zhou Q, Chen Z, Sims PJ, Wiedmer T, and Chen GQ (2004) Protein kinase Cd mediates retinoic acid and phorbol myristate acetate-induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation. Blood 104:3731-3738

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 nuclear 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 controls its distribution betweeen nucleus and plasma membrane. Biochemistry 42:1227-1233

Sun J, Nanjundan M, Pike LJ, Wiedmer T, and Sims PJ (2002). Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and interacts with the epidermal growth factor receptor. Biochemistry 41:6338-6345

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

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

Sims PJ and Wiedmer T (2001). Unraveling the mysteries of phospholipid scrambling. Thromb. Haemost. 86:266-275

Wiedmer T, Zhou Q, Kwoh DY, and Sims PJ (2000). Identification of three new members of the phospholipid scramblase gene family. Biochim. Biophys. Acta 1467:244-253

Zhou Q, Sims PJ, and Wiedmer T (1998). Identity of a conserved motif in phospholipid scramblase that is required for Ca2+-accelerated transbilayer movement of membrane phospholipids.. Biochemistry 37:2356-2360

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