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Therese Wiedmer, Ph.D.

Therese Wiedmer, Ph.D.

About Me

Faculty Appointments

Professor Emeritus - Department of Medicine (SMD)

Credentials

Education

PhD | Switzerland-Univ of Bern. Biochemistry. 1977

BS | Switzerland-Univ of Bern. Chemistry. 1973

Awards

Merrick Award for scientific Research
Oklahoma Medical Research Foundation 1989

Fellow, American Heart Association.

Research

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+....
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 these proteins than their putative role in mediating transbilayer lipid movement. PLSCR1 -- and possibly other members of the PLSCR gene family -- plays a role in modulating the signal transduction through multiple growth factor receptors, and is itself transcriptionally upregulated through these same growth factor receptor pathways. We also 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.

Publications

Journal Articles

Regulation of the tyrosine phosphorylation of Phospholipid Scramblase 1 in mast cells that are stimulated through the high-affinity IgE receptor.

Kassas A, Moura IC, Yamashita Y, Scheffel J, Guérin-Marchand C, Blank U, Sims PJ, Wiedmer T, Monteiro RC, Rivera J, Charles N, Benhamou M

PloS one.. 2014 9 (10):e109800. Epub 10/07/2014.

Identification of key regulatory pathways of myeloid differentiation using an mESC-based karyotypically normal cell model.

Li D, Yang H, Nan H, Liu P, Pang S, Zhao Q, Karni R, Kamps MP, Xu Y, Zhou J, Wiedmer T, Sims PJ, Wang F

Blood.. 2012 December 6120 (24):4712-9. Epub 10/18/2012.

Nuclear phospholipid scramblase 1 prolongs the mitotic expansion of granulocyte precursors during G-CSF-induced granulopoiesis.

Chen CW, Sowden M, Zhao Q, Wiedmer T, Sims PJ

Journal of leukocyte biology.. 2011 August 90 (2):221-33. Epub 03/29/2011.

Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors.

Bateman A, Finn RD, Sims PJ, Wiedmer T, Biegert A, Söding J

Bioinformatics.. 2009 January 1525 (2):159-62. Epub 11/13/2008.

Expression of the phospholipid scramblase (PLSCR) gene family during the acute phase response.

Lu B, Sims PJ, Wiedmer T, Moser AH, Shigenaga JK, Grunfeld C, Feingold KR

Biochimica et biophysica acta.. 2007 September 1771 (9):1177-85. Epub 05/26/2007.

Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice.

Mutch DM, O'Maille G, Wikoff WR, Wiedmer T, Sims PJ, Siuzdak G

Genome biology.. 2007 8 (3):R38. Epub 1900 01 01.

Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cells.

Huang Y, Zhao Q, Zhou CX, Gu ZM, Li D, Xu HZ, Wiedmer T, Sims PJ, Zhao KW, Chen GQ

Oncogene.. 2006 October 2625 (50):6618-27. Epub 05/15/2006.

Phospholipid scramblase 1 binds to the promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene to enhance its expression.

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

The Journal of biological chemistry.. 2005 October 14280 (41):35062-8. Epub 08/09/2005.

Protein kinase Cdelta mediates retinoic acid and phorbol myristate acetate-induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation.

Zhao KW, Li X, Zhao Q, Huang Y, Li D, Peng ZG, Shen WZ, Zhao J, Zhou Q, Chen Z, Sims PJ, Wiedmer T, Chen GQ

Blood.. 2004 December 1104 (12):3731-8. Epub 08/12/2004.

Adiposity, dyslipidemia, and insulin resistance in mice with targeted deletion of phospholipid scramblase 3 (PLSCR3).

Wiedmer T, Zhao J, Li L, Zhou Q, Hevener A, Olefsky JM, Curtiss LK, Sims PJ

Proceedings of the National Academy of Sciences of the United States of America.. 2004 September 7101 (36):13296-301. Epub 08/24/2004.

Phospholipid scramblase 1 potentiates the antiviral activity of interferon.

Dong B, Zhou Q, Zhao J, Zhou A, Harty RN, Bose S, Banerjee A, Slee R, Guenther J, Williams BR, Wiedmer T, Sims PJ, Silverman RH

Journal of virology.. 2004 September 78 (17):8983-93. Epub 1900 01 01.

Phospholipid scramblase 1 is imported into the nucleus by a receptor-mediated pathway and interacts with DNA.

Ben-Efraim I, Zhou Q, Wiedmer T, Gerace L, Sims PJ

Biochemistry.. 2004 March 3043 (12):3518-26. Epub 1900 01 01.

Plasma membrane phospholipid scramblase 1 promotes EGF-dependent activation of c-Src through the epidermal growth factor receptor.

Nanjundan M, Sun J, Zhao J, Zhou Q, Sims PJ, Wiedmer T

The Journal of biological chemistry.. 2003 September 26278 (39):37413-8. Epub 07/18/2003.

Caspase-independent exposure of aminophospholipids and tyrosine phosphorylation in bicarbonate responsive human sperm cells.

de Vries KJ, Wiedmer T, Sims PJ, Gadella BM

Biology of reproduction.. 2003 June 68 (6):2122-34. Epub 01/22/2003.

Palmitoylation of phospholipid scramblase 1 controls its distribution between nucleus and plasma membrane.

Wiedmer T, Zhao J, Nanjundan M, Sims PJ

Biochemistry.. 2003 February 1142 (5):1227-33. Epub 1900 01 01.

Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1.

Zhou Q, Zhao J, Wiedmer T, Sims PJ

Blood.. 2002 June 199 (11):4030-8. Epub 1900 01 01.

Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and interacts with the epidermal growth factor receptor.

Sun J, Nanjundan M, Pike LJ, Wiedmer T, Sims PJ

Biochemistry.. 2002 May 2141 (20):6338-45. Epub 1900 01 01.

Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1.

Silverman RH, Halloum A, Zhou A, Dong B, Al-Zoghaibi F, Kushner D, Zhou Q, Zhao J, Wiedmer T, Sims PJ

Cancer research.. 2002 January 1562 (2):397-402. Epub 1900 01 01.

c-Abl tyrosine kinase binds and phosphorylates phospholipid scramblase 1.

Sun J, Zhao J, Schwartz MA, Wang JY, Wiedmer T, Sims PJ

The Journal of biological chemistry.. 2001 August 3276 (31):28984-90. Epub 06/04/2001.

Unraveling the mysteries of phospholipid scrambling.

Sims PJ, Wiedmer T

Thrombosis and haemostasis.. 2001 July 86 (1):266-75. Epub 1900 01 01.

Identification of three new members of the phospholipid scramblase gene family.

Wiedmer T, Zhou Q, Kwoh DY, Sims PJ

Biochimica et biophysica acta.. 2000 July 311467 (1):244-53. Epub 1900 01 01.

Sphingomyelin hydrolysis to ceramide during the execution phase of apoptosis results from phospholipid scrambling and alters cell-surface morphology.

Tepper AD, Ruurs P, Wiedmer T, Sims PJ, Borst J, van Blitterswijk WJ

The Journal of cell biology.. 2000 July 10150 (1):155-64. Epub 1900 01 01.

Transcriptional control of the human plasma membrane phospholipid scramblase 1 gene is mediated by interferon-alpha.

Zhou Q, Zhao J, Al-Zoghaibi F, Zhou A, Wiedmer T, Silverman RH, Sims PJ

Blood.. 2000 April 1595 (8):2593-9. Epub 1900 01 01.

Phosphatidylserine exposure during apoptosis is a cell-type-specific event and does not correlate with plasma membrane phospholipid scramblase expression.

Fadeel B, Gleiss B, Högstrand K, Chandra J, Wiedmer T, Sims PJ, Henter JI, Orrenius S, Samali A

Biochemical and biophysical research communications.. 1999 December 20266 (2):504-11. Epub 1900 01 01.

Complement Biology

Sims, PJ and Wiedmer, T (R. Hoffman, E.J. Benz, H.J. Cohen, S.J. Shattil, B. Furie, L.E. Silberstein, P. McGlave, eds).

Hematology: Basic Principles and Practice. 1999; : 651-667.

Change in conformation of plasma membrane phospholipid scramblase induced by occupancy of its Ca2+ binding site.

Stout JG, Zhou Q, Wiedmer T, Sims PJ

Biochemistry.. 1998 October 2037 (42):14860-6. Epub 1900 01 01.

Expression of proteins controlling transbilayer movement of plasma membrane phospholipids in the B lymphocytes from a patient with Scott syndrome.

Zhou Q, Sims PJ, Wiedmer T

Blood.. 1998 September 192 (5):1707-12. Epub 1900 01 01.

Palmitoylation of phospholipid scramblase is required for normal function in promoting Ca2+-activated transbilayer movement of membrane phospholipids.

Zhao J, Zhou Q, Wiedmer T, Sims PJ

Biochemistry.. 1998 May 537 (18):6361-6. Epub 1900 01 01.

Level of expression of phospholipid scramblase regulates induced movement of phosphatidylserine to the cell surface.

Zhao J, Zhou Q, Wiedmer T, Sims PJ

The Journal of biological chemistry.. 1998 March 20273 (12):6603-6. Epub 1900 01 01.

Identity of a conserved motif in phospholipid scramblase that is required for Ca2+-accelerated transbilayer movement of membrane phospholipids.

Zhou Q, Sims PJ, Wiedmer T

Biochemistry.. 1998 February 2437 (8):2356-60. Epub 1900 01 01.

Molecular cloning of human plasma membrane phospholipid scramblase. A protein mediating transbilayer movement of plasma membrane phospholipids.

Zhou Q, Zhao J, Stout JG, Luhm RA, Wiedmer T, Sims PJ

The Journal of biological chemistry.. 1997 July 18272 (29):18240-4. Epub 1900 01 01.

Production and characterization of a mutant cell line defective in aminophospholipid translocase.

Zhao J, Sims PJ, Wiedmer T

Biochimica et biophysica acta.. 1997 June 51357 (1):57-64. Epub 1900 01 01.

Scott syndrome erythrocytes contain a membrane protein capable of mediating Ca2+-dependent transbilayer migration of membrane phospholipids.

Stout JG, Bassé F, Luhm RA, Weiss HJ, Wiedmer T, Sims PJ

The Journal of clinical investigation.. 1997 May 199 (9):2232-8. Epub 1900 01 01.

Isolation of an erythrocyte membrane protein that mediates Ca2+-dependent transbilayer movement of phospholipid.

Bassé F, Stout JG, Sims PJ, Wiedmer T

The Journal of biological chemistry.. 1996 July 19271 (29):17205-10. Epub 1900 01 01.

Induction of cellular procoagulant activity by the membrane attack complex of complement.

Sims PJ, Wiedmer T

Seminars in cell biology. 1995 October 6 (5):275-82. Epub 1900 01 01.

The complex of phosphatidylinositol 4,5-bisphosphate and calcium ions is not responsible for Ca2+-induced loss of phospholipid asymmetry in the human erythrocyte: a study in Scott syndrome, a disorder of calcium-induced phospholipid scrambling.

Bevers EM, Wiedmer T, Comfurius P, Zhao J, Smeets EF, Schlegel RA, Schroit AJ, Weiss HJ, Williamson P, Zwaal RF, Sims PJ

Blood.. 1995 September 186 (5):1983-91. Epub 1900 01 01.

Production and characterization of transformed B-lymphocytes expressing the membrane defect of Scott syndrome.

Kojima H, Newton-Nash D, Weiss HJ, Zhao J, Sims PJ, Wiedmer T

The Journal of clinical investigation.. 1994 December 94 (6):2237-44. Epub 1900 01 01.

Identity of a peptide domain of human C9 that is bound by the cell-surface complement inhibitor, CD59.

Chang CP, Hüsler T, Zhao J, Wiedmer T, Sims PJ

The Journal of biological chemistry.. 1994 October 21269 (42):26424-30. Epub 1900 01 01.

Immunology: Complement Biology

Sims PJ and Wiedmer T (E. Benz, H. Cohen, B. Furie, R. Hoffman, S. Shattil, eds). Churchill Livingstone, New York.

Hematology: Basic Principles and Practice. 1994; Chapter 12.

Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria.

Wiedmer T, Hall SE, Ortel TL, Kane WH, Rosse WF, Sims PJ

Blood.. 1993 August 1582 (4):1192-6. Epub 1900 01 01.

Contribution of platelet microparticle formation and granule secretion to the transmembrane migration of phosphatidylserine.

Chang CP, Zhao J, Wiedmer T, Sims PJ

The Journal of biological chemistry.. 1993 April 5268 (10):7171-8. Epub 1900 01 01.

Binding of anticoagulant vitamin K-dependent protein S to platelet-derived microparticles.

Dahlbäck B, Wiedmer T, Sims PJ

Biochemistry.. 1992 December 2931 (51):12769-77. Epub 1900 01 01.

Regulation of glycoprotein IIb-IIIa receptor function studied with platelets permeabilized by the pore-forming complement proteins C5b-9.

Shattil SJ, Cunningham M, Wiedmer T, Zhao J, Sims PJ, Brass LF

The Journal of biological chemistry.. 1992 September 15267 (26):18424-31. Epub 1900 01 01.

Inhibition of the complement membrane attack complex by the galactose-specific adhesion of Entamoeba histolytica.

Braga LL, Ninomiya H, McCoy JJ, Eacker S, Wiedmer T, Pham C, Wood S, Sims PJ, Petri WA

The Journal of clinical investigation.. 1992 September 90 (3):1131-7. Epub 1900 01 01.

Defective Ca(2+)-induced microvesiculation and deficient expression of procoagulant activity in erythrocytes from a patient with a bleeding disorder: a study of the red blood cells of Scott syndrome.

Bevers EM, Wiedmer T, Comfurius P, Shattil SJ, Weiss HJ, Zwaal RF, Sims PJ

Blood.. 1992 January 1579 (2):380-8. Epub 1900 01 01.

Inhibition of the complement membrane attack complex by the galactose-specific adhesin of Entamoeba histolytica.

Braga LL, Ninomiya H, McCoy JJ, Adal K, Wiedmer T, Pham C, Sims PJ, Petri WA

Archives of medical research.. 1992 23 (2):133. Epub 1900 01 01.

Participation of protein kinases in complement C5b-9-induced shedding of platelet plasma membrane vesicles.

Wiedmer T, Sims PJ

Blood.. 1991 December 178 (11):2880-6. Epub 1900 01 01.

Platelet-derived microparticles express high affinity receptors for factor VIII.

Gilbert GE, Sims PJ, Wiedmer T, Furie B, Furie BC, Shattil SJ

The Journal of biological chemistry.. 1991 September 15266 (26):17261-8. Epub 1900 01 01.

The response of human platelets to activated components of the complement system.

Sims PJ, Wiedmer T

Immunology today.. 1991 September 12 (9):338-42. Epub 1900 01 01.

Identification of a platelet dense granule membrane protein that is deficient in a patient with the Hermansky-Pudlak syndrome.

Gerrard JM, Lint D, Sims PJ, Wiedmer T, Fugate RD, McMillan E, Robertson C, Israels SJ

Blood.. 1991 January 177 (1):101-12. Epub 1900 01 01.

Role of calcium and calpain in complement-induced vesiculation of the platelet plasma membrane and in the exposure of the platelet factor Va receptor.

Wiedmer T, Shattil SJ, Cunningham M, Sims PJ

Biochemistry.. 1990 January 2329 (3):623-32. Epub 1900 01 01.

Regulatory control of complement on blood platelets. Modulation of platelet procoagulant responses by a membrane inhibitor of the C5b-9 complex.

Sims PJ, Rollins SA, Wiedmer T

The Journal of biological chemistry.. 1989 November 15264 (32):19228-35. Epub 1900 01 01.

Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity.

Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ

The Journal of biological chemistry.. 1989 October 15264 (29):17049-57. Epub 1900 01 01.

The secretory release reaction initiated by complement proteins C5b-9 occurs without platelet aggregation through glycoprotein IIb-IIIa.

Ando B, Wiedmer T, Sims PJ

Blood.. 1989 February 73 (2):462-7. Epub 1900 01 01.

Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity.

Sims PJ, Faioni EM, Wiedmer T, Shattil SJ

The Journal of biological chemistry.. 1988 December 5263 (34):18205-12. Epub 1900 01 01.

Complement proteins C5b-9 initiate secretion of platelet storage granules without increased binding of fibrinogen or von Willebrand factor to newly expressed cell surface GPIIb-IIIa.

Ando B, Wiedmer T, Hamilton KK, Sims PJ

The Journal of biological chemistry.. 1988 August 25263 (24):11907-14. Epub 1900 01 01.

Complement C5b-9-stimulated platelet secretion is associated with a Ca2+-initiated activation of cellular protein kinases.

Wiedmer T, Ando B, Sims PJ

The Journal of biological chemistry.. 1987 October 5262 (28):13674-81. Epub 1900 01 01.

On the mechanism by which complement proteins C5b-9 increase platelet prothrombinase activity.

Wiedmer T, Esmon CT, Sims PJ

The Journal of biological chemistry.. 1986 November 5261 (31):14587-92. Epub 1900 01 01.

Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase.

Wiedmer T, Esmon CT, Sims PJ

Blood.. 1986 October 68 (4):875-80. Epub 1900 01 01.

Repolarization of the membrane potential of blood platelets after complement damage: evidence for a Ca++ -dependent exocytotic elimination of C5b-9 pores.

Sims PJ, Wiedmer T

Blood.. 1986 August 68 (2):556-61. Epub 1900 01 01.

Single-channel analysis of the conductance fluctuations induced in lipid bilayer membranes by complement proteins C5b-9.

Benz R, Schmid A, Wiedmer T, Sims PJ

The Journal of membrane biology.. 1986 94 (1):37-45. Epub 1900 01 01.

Effect of complement proteins C5b-9 on blood platelets. Evidence for reversible depolarization of membrane potential.

Wiedmer T, Sims PJ

The Journal of biological chemistry.. 1985 July 5260 (13):8014-9. Epub 1900 01 01.

Fluorescence resonance energy transfer study of the associative state of membrane-bound complexes of complement proteins C5b-8.

Cheng KH, Wiedmer T, Sims PJ

The Journal of immunology : official journal of the American Association of Immunologists.. 1985 July 135 (1):459-64. Epub 1900 01 01.

Characterization of the complement sensitivity of paroxysmal nocturnal hemoglobinuria erythrocytes.

Parker CJ, Wiedmer T, Sims PJ, Rosse WF

The Journal of clinical investigation.. 1985 June 75 (6):2074-84. Epub 1900 01 01.

Cyanine dye fluorescence used to measure membrane potential changes due to the assembly of complement proteins C5b-9.

Wiedmer T, Sims PJ

The Journal of membrane biology.. 1985 84 (3):249-58. Epub 1900 01 01.

Electron spin resonance and steady-state fluorescence polarization studies of lipid bilayers containing integral proteins.

Pink DA, Chapman D, Laidlaw DJ, Wiedmer T

Biochemistry.. 1984 August 2823 (18):4051-8. Epub 1900 01 01.

Kinetics of polymerization of a fluoresceinated derivative of complement protein C9 by the membrane-bound complex of complement proteins C5b-8.

Sims PJ, Wiedmer T

Biochemistry.. 1984 July 323 (14):3260-7. Epub 1900 01 01.

The influence of electrochemical gradients of Na+ and K+ upon the membrane binding and pore forming activity of the terminal complement proteins.

Sims PJ, Wiedmer T

The Journal of membrane biology.. 1984 78 (2):169-76. Epub 1900 01 01.

Properties of the M antigen solubilized from genetically high potassium sheep red cells.

Wiedmer T, Lauf PK

Membrane biochemistry. 1981 4 (1):31-47. Epub 1900 01 01.

Effects of amphiphiles on structure and activity of human erythrocyte membrane acetylcholinesterase.

Wiedmer T, Di Francesco C, Brodbeck U

European journal of biochemistry. 1979 December 102 (1):59-64. Epub 1900 01 01.

Interactions of acetylcholine receptor and acetylcholinesterase with lipid monolayers.

Wiedmer T, Brodbeck U, Zahler P, Fulpius BW

Biochimica et biophysica acta.. 1978 January 19506 (2):161-72. Epub 1900 01 01.

Electrophorus Electricus

Brodbeck, U.; Ott, P. and Wiedmer, T.

Croat.Chem.Acta. 1975; 47: 201, 210.

Binding of acetylcholinesterases to concanavalin A.

Wiedmer T, Gentinetta R, Brodbeck U

FEBS letters.. 1974 October 1547 (2):260-3. Epub 1900 01 01.

Chlamydomonas Reinhardi

Boschetti, A.; Niggli, V.; Otz U. and Wiedmer, T.

Physiologia P1. 1974; 31: 169-174.