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Marc Monestier, MD, PhDMarc Monestier, MD, PhD

 

Director, Temple Autoimmunity Center

Professor, Microbiology and Immunology

Telephone:  215-707-1744

Fax:  215-707-5149

Email: marc.monestier@temple.edu

 

Temple Autoimmunity Center

Department of Microbiology and Immunology

 

Educational Background:

 

University of Lyon

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Research Interests:

 

Dr. Monestier's research is focused on the elucidation of the mechanisms responsible for the development of autoimmune diseases. Exposure to various drugs and chemicals can elicit autoimmune disease in both humans and experimental animals. For instance, an environmental pollutant such as mercury induces in susceptible mouse strains autoantibodies to nucleolar antigens similar to those seen in human scleroderma. We are investigating the regulation of disease development in this mouse model. Our efforts are focused on the role of co-stimulatory molecules, regulatory T cells and Toll-like receptors in controlling susceptibility to chemical agents. We are also exploring the direct effect of heavy metals on B cells and on dendritic cell function. Studies into the mechanisms of chemically-induced autoimmunity are particularly meaningful since environmental factors have been implicated in the pathogenesis of systemic autoimmunity.

 

Autoantibodies to negatively-charged phospholipids are associated with venous and arterial thrombosis and with spontaneous abortions. In addition, recent evidence suggests that antiphospholipid antibodies are present during atherosclerosis and that they may modulate the disease. We have generated and characterized the binding properties of a large panel of anti-phospholipid mouse monoclonal antibodies. We have observed that one of these monoclonal antibodies decreases plaque formation when passively administered into atherosclerosis-prone mice. We are investigating the mechanisms responsible for the protective effects of this antibody as well as the possibility of actively manipulating the immune system to prevent atherosclerosis.

 

The autoimmune response to chromatin is at the core of systemic autoimmune syndromes such as lupus. We have shown that autoantibodies recognize a variety of three-dimensional determinants that result from the ordered association of chromatin molecules such as histones and DNA. These antibodies to nucleosome epitopes are characterized by the presence of numerous arginines in their variable regions. These cationic residues are important for binding to the acidic DNA component of the nucleosome and are often the result of unusual immunoglobulin heavy chain gene rearrangements.

 

We have recently shown that these unusual immunoglobulin gene rearrangements occur more frequently in autoimmune than in normal mice and we are exploring the mechanisms responsible for this intrinsic B cell defect in autoimmunity.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

25122007. Jha V, Workman CJ, McGaha TL, Li L, Vas J, Vignali DA, Monestier M, Lymphocyte Activation Gene-3 (LAG-3) Negatively Regulates Environmentally-Induced Autoimmunity. PLoS One 9:8(e104484)2014

22942426. Zizzo G, Hilliard BA, Monestier M, Cohen PL, Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. J Immunol 189:7(3508-20)2012 Oct 1

22127758. Jog NR, Frisoni L, Shi Q, Monestier M, Hernandez S, Craft J, Prak ET, Caricchio R, Caspase-activated DNase is required for maintenance of tolerance to lupus nuclear autoantigens. Arthritis Rheum 64:4(1247-56)2012 Apr

19709928. Schiraldi M, Monestier M, How can a chemical element elicit complex immunopathology? Lessons from mercury-induced autoimmunity. Trends Immunol 30:10(502-9)2009 Oct

19076354. Vas J, Monestier M, Immunology of mercury. Ann N Y Acad Sci 1143:(240-67)2008 Nov

18981095. Vas J, Mattner J, Richardson S, Ndonye R, Gaughan JP, Howell A, Monestier M, Regulatory roles for NKT cell ligands in environmentally induced autoimmunity. J Immunol 181:10(6779-88)2008 Nov 15

17127454. Nicolo D, Varadhachary AS, Monestier M, Atherosclerosis, antiphospholipid syndrome, and antiphospholipid antibodies. Front Biosci 12:(2171-82)2007 Jan 1

16237113. Zheng Y, Gallucci S, Gaughan JP, Gross JA, Monestier M, A role for B cell-activating factor of the TNF family in chemically induced autoimmunity. J Immunol 175:9(6163-8)2005 Nov 1

15829271. Rowley B, Monestier M, Mechanisms of heavy metal-induced autoimmunity. Mol Immunol 42:7(833-8)2005 May

15728528. Zheng Y, Jost M, Gaughan JP, Class R, Coyle AJ, Monestier M, ICOS-B7 homologous protein interactions are necessary for mercury-induced autoimmunity. J Immunol 174:5(3117-21)2005 Mar 1

15240162. Nicolo D, Monestier M, Antiphospholipid antibodies and atherosclerosis. Clin Immunol 112:2(183-9)2004 Aug

14558104. Nicolo D, Goldman BI, Monestier M, Reduction of atherosclerosis in low-density lipoprotein receptor-deficient mice by passive administration of antiphospholipid antibody. Arthritis Rheum 48:10(2974-8)2003 Oct

12874254. Zheng Y, Monestier M, Inhibitory signal override increases susceptibility to mercury-induced autoimmunity. J Immunol 171:3(1596-601)2003 Aug 1

11975753. Monestier M, Zouali M, Receptor revision and systemic lupus. Scand J Immunol 55:5(425-31)2002 May

11882027. Bagenstose LM, Class R, Salgame P, Monestier M, B7-1 and B7-2 co-stimulatory molecules are required for mercury-induced autoimmunity. Clin Exp Immunol 127:1(12-9)2002 Jan

11747355. Varadhachary AS, Monestier M, Salgame P, Reciprocal induction of IL-10 and IL-12 from macrophages by low-density lipoprotein and its oxidized forms. Cell Immunol 213:1(45-51)2001 Oct 10

11737666. Bagenstose LM, Mentink-Kane MM, Brittingham A, Mosser DM, Monestier M, Mercury enhances susceptibility to murine leishmaniasis. Parasite Immunol 23:12(633-40)2001 Dec

11429325. Klonowski KD, Monestier M, Ig heavy-chain gene revision: leaping towards autoimmunity. Trends Immunol 22:7(400-5)2001 Jul

11035088. Klonowski KD, Monestier M, Heavy chain revision in MRL mice: a potential mechanism for the development of autoreactive B cell precursors. J Immunol 165:8(4487-93)2000 Oct 15

10788471. Monestier M, Decker P, Briand JP, Gabriel JL, Muller S, Molecular and structural properties of three autoimmune IgG monoclonal antibodies to histone H2B. J Biol Chem 275:18(13558-63)2000 May 5

10502547. Bagenstose LM, Salgame P, Monestier M, Cytokine regulation of a rodent model of mercuric chloride-induced autoimmunity. Environ Health Perspect 107 Suppl 5:(807-10)1999 Oct

10467984. Bagenstose LM, Salgame P, Monestier M, Murine mercury-induced autoimmunity: a model of chemically related autoimmunity in humans. Immunol Res 20:1(67-78)1999

9973414. Klonowski KD, Primiano LL, Monestier M, Atypical VH-D-JH rearrangements in newborn autoimmune MRL mice. J Immunol 162:3(1566-72)1999 Feb 1

9764596. Bagenstose LM, Salgame P, Monestier M, Mercury-induced autoimmunity in the absence of IL-4. Clin Exp Immunol 114:1(9-12)1998 Oct

9469417. Bagenstose LM, Salgame P, Monestier M, IL-12 down-regulates autoantibody production in mercury-induced autoimmunity. J Immunol 160:4(1612-7)1998 Feb 15

9016614. Salgame P, Varadhachary AS, Primiano LL, Fincke JE, Muller S, Monestier M, An ELISA for detection of apoptosis. Nucleic Acids Res 25:3(680-1)1997 Feb 1

9182875. Monestier M, Stemmer C, Ong GL, Muller S, Induction of anti-polycation antibodies in H-2s mice by immunization with nuclear antigens. Mol Immunol 34:1(39-51)1997 Jan

8990087. Monestier M, Autoantibodies to nucleosomes and histone-DNA complexes. Methods 11:1(36-43)1997 Jan

8786329. Monestier M, Kandiah DA, Kouts S, Novick KE, Ong GL, Radic MZ, Krilis SA, Monoclonal antibodies from NZW x BXSB F1 mice to beta2 glycoprotein I and cardiolipin. Species specificity and charge-dependent binding. J Immunol 156:7(2631-41)1996 Apr 1

8604228. Monestier M, Novick KE, Specificities and genetic characteristics of nucleosome-reactive antibodies from autoimmune mice. Mol Immunol 33:1(89-99)1996 Jan

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graduate students :

Vibha Jha

Sun-Ah Kang

Liping Li

Eduardo Piaggio

Michael Schiraldi

Jaya Vas

Certain Recent Graduates:


Lee M. Bagenstose, PhD

TRI, Inc.

Bethesda, MD


Kimberly D. Klonowski, PhD

Assistant Professor

University of Georgia

Athens, GA


Danielle M. Nicolo, MD, PhD

Internal Medicine Resident

Temple University


Benjamin M. Rowley, PhD

Assistant Professor

University of Central Arkansas

Conway, AR


Arun S. Varadhachary, MD, PhD

Neurology Resident

Washington University

St. Louis, MO


Yan Zheng, PhD

Postdoctoral Fellow

Genentech

South San Francisco, CA


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grant support :

 

Current or Recent Grant Support of Active Projects:

 

Marc Monestier, MD, PhD as Principal Investigator:

National Institutes of Health, R01 ES09409
Immunotoxicology of Mercury in Genetically Susceptible Mice

 

National Institutes of Health, R01 ES12464
Immunotoxicologic Effects of Mercury on B Cells

Marc Monestier, MD, PhD as Co-Investigator:

National Institutes of Health, T32 A107101, C. D. Platsoucas, PhD, Principal Investigator/Program Director; Microbiology and Immunology Training Program

 

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