David Clark

, PhD, MD, FRCPC, FRCP(Edin)

Associate Member
Pathology and Molecular Medicine

Professor, Medicine
Associate Member, Obstetrics & Gynecology

Medical Oncology Consultant, Juravinski Cancer Center

McMaster University
3V39 Health Sciences Centre
905-521-2100 ext. 76376/76375
clarkd@mcmaster.ca

Education and Professional Standing

FRCP(Edin) Internal Medicine, 2001
PhD (Univ. Toronto), Medical Sciences, 1977
FRCP(C) Internal Medicine, 1974
Dipl ABIM, Internal Medicine, 1972
MD (Univ Western Ontario) 1967

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Interests

Research Focus

• Immunology of Reproduction
• Immunology of pregnancy. Fetus rejection in recurrent miscarriage and infertility. Prevention of pregnancy failure. The fetus as a model of a successful tumor.
• Characterization of molecules expressed by fetal trophoblast and maternal decidual cells that determine success or failure in pregnant mice and humans; FGL2, (CD200), MD-1 and toll receptors.
• Role of FGL2 and CD200 in autoimmune arthritis and viral hepatitis
• Role of gd T and NK-gd T cells. In vitro and in vivo studies in cellular and molecular immunology.
• Alteration of pregnancy outcome by vaccines and recombinant cytokines: analysis of mechanism. Mechanism determining susceptibility of cancer cells to rejections and analysis of parallel strategies of evasion as defined by studies of pregnancy.
• Cell culture, killer cell assays, in situ hybridization, immunohistochemistry, northern and western blotting, subtractive hybridization, ELISA and colony assays.

Clinical Focus

Dr. Clark’s clinical focus is in the areas of:

• Solid tumor treatment
• Monoclonal antibodies and small molecular inhibitors in cancer therapy.
• Primary gastrointestinal cancers and breast cancers

Academic Interests

Dr. Clark is involved in several areas of teaching within the Faculty of Health Science including:

• Undergraduate Medical Program, Tutor and Clinical Preceptor
• Post-graduate Medical Residency Program, Clinical Preceptor
• Medical Sciences Graduate Program, MS715: Reproductive Immunology
• Bachelor of Health Sciences Undergraduate Program , HTH SCI 4II3: Advanced Topics in Immunology

Dr. Clark serves on a PhD Program Committee, the FHS/HHS REB, and on editorial boards.

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Team Members

• Petra C. Arck, Canada Research Chair in Neuroimmunology, McMaster University, and Associate Prof. Medicine
• Gary A. Levy, Director, Multiorgan Transplant Program and Novartis Chair, Professor of Medicine, Dept. Medicine, Univ. Toronto.
• Reginald M. Gorczynski, Professor of Surgery, Univ. Toronto
• Gerard Chaouat, Maitre de Recherche, INSERM U, Clamart, France

Selected Publications

• Clark DA. Tolerance Signaling Molecules. 2005. Chemical Immunol. Allergy 89: 36-48.
• Clark DA. 2005. Altered fertility as seen as a problem in immunoregulation. In: Gorczynski, RM (ed). Altered Immunoregulation and Human Disease.   Research Signpost; Kerala (India), pp 353-368.
• Clark DA. 2008. Commentary: Should anti-TNF-α therapy be offered to patients with infertility and recurrent spontaneous abortion? Amer. J. Reprod. Immunol. 2009; 61: 107-112. Doi: 10.1111/j.1600-0897.2008.00680.x
• Terness P, Kallikourdis M, Betz AG, Rabinovich G, Saito S, Clark DA. 2007. Tolerance signalling molecules and pregnancy: IDO, galectins, and the renaissance of regulatory T cells. Amer. J. Reprod. Immunol. 58: 238-254.
• Van den Heuvel MJ, Peralta CG, Hatta K, Han VK, Clark DA. 2007. Decline in number of elevated blood CD3+ CD56+ NKT cells in response to IVIG treatment correlates with successful pregnancy. Amer. J. Reprod. Immunol. 58: 447-457.
• Shalev I, Liu H, Koscik C, Bartczak A, Javadi M, Wong KM, Maknojia A, Hr W, Liu MF, Dia J, Winter EW, Manuel J, McCarthy D, Cattral M, Gommerman J, Clark DA, Phillips MJ, Gorczynski RR, Zhang L, Downey G, Grant D, Cybulski, MI, Levy G. 2008. Targeted deletion of fg12 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis. J. Immunol. 180: 249-260.
• Clark DA, Gorczynski RM, Blajchman MA. 2008. Transfusion-related immunomodulation due to peripheral blood dendritic cells expressing the CD200 tolerance signalling molecule and alloangiten: stimulation of tumor nodule formation and growth by TGF-β in a murine model. Transfusion 48: 814-821.
• Clark DA. 2008. Immunological factors in pregnancy wastage: Fact or Fiction. Amer. J. Reprod Immunol. 59: 277-300.
• Clark DA, Wong K, Banwatt D, Chen Z, Liu J, Gorczynski RM, Blajchman MA. 2008. CD200-dependent and non-CD200 dependent pathways of NK cell suppression by human IVIG. J. Assist. Rreprod. Genet. 25: 67-72 (on line Feb 7, 2008 doi 10.1007/s10815-008-9202-9)
• Clark DA, Fernandez J, Banwatt D. 2008. Prevention of sponsaneous abortion in the CBAxDBA/2 mouse model by intravaginal TGF- β and local recruitment od CD4+8+FOXP3+ cells. Amer. J. Reprod. Immunol. 59: 525-534.
• Yu G, Sun Y, Foerster K, Manuel J, Molina H, Levy GA, Gorczynski, RM, Clark DA.2008. LPS-induced murine abortions require C5 but not C3, and are prevented by upregulating expression of the CD200 tolerance signalling molecule. Amer. J. Reprod. Immunol. 60:135-140.
• Liu H, Shavell I, Manuel J, He W, Leung E, Crookshank J, Liu M-F, Diao J, Cattral M, Clark DA, Isenman DE, Gorczynski RM, Grant DR, Zhang L,  Phillips M, Cybulsky MI, Levy GA. 2008. The FGL2-FcγRIIB pathway: a novel mechanism leading to immunosuppression. Eur. J. Immunol. 38: 3114-3126.
• Clark DA. 2009. An observational study on the role of cell surface CD200 in efficacy of paternal mononuclear leukocyte immunotherapy in recurrent pregnancy loss. Amer. J. Reprod. Immunol. 61: 75-84. doi: 10.1111/j.1600-0897.2008.00665.x
• Clark DA, Chaouat G, Banwatt D, Friebe A, Arck PC. 2008. Ecology of danger-dependent cytokine-boosted spontaneous abortion in the BDA x DBA/2 mouse model. II. Fecal LPS levels in colonies with different basal abortion rates. Amer. J. Reprod. Immunol. 60: 529-533.
• Shalev I, Wong KM, Foerster K, Zhu Y, Chan C, Maknojia A, Liu MF, Zhang J. Ma X-Z, Zang J, Gao JF, Liu H, “Selzner N, Clark DA, Adeyi O, Phillips MJ, Gorczynski RM, Grant D, McGilvary I, Levy G. 2009. FGL2 the novel Treg effector molecule plays a critical role in the outcome of murine fulminant viral hepatitis. Heptology. 49: 387-397. doi: 10.1002/hep.2264 (Oct 2008)