Raphael Clynes, M.D., Ph.D.
Raphael Clynes, M.D., Ph.D.
Dr. Clynes is a physician-scientist and cellular immunologist who studies the contributions of immunoreceptors to dendritic cell regulation in health and disease. Murine models provide the foundation for his funded work but translational clinical studies are a significant focus as well.
Dr. Clynes studies demonstrated that Fc receptor engagement on effector cells was critical to immune complex pathogenesis in hemolytic anemia, alveolitis and lupus nephritis. His work in antitumor antibodies established the genetic evidence supporting the paradigm that engineered therapeutic antibodies should engage activatory over inhibitory Fc receptors.
His research on the immunoregulation of dendritic cells inimmunity and inflammation has demonstrated that autoantibodies participate in pathogenesis via Fc receptors on dendritic cells by driving T cell responses to islet antigens. In therapeutic maneuvers attempting to block this pathogenic pathway, Dr. Clynes has demonstrated by both genetic and pharmacologic approaches that the Syk kinase is an attractive and effective target in the treatment of Type I diabetes.
Dr. Clynes’ clinical research has provided evidence for the relevance of FcR engagement to antitumor antibody efficacy by showing that B and T cell antitumor immunity develop in Trastuzumab-treated patients in a manner correlating with favorable clinical outcome. Dr. Clynes is PI or co-PI on three NIH funded clinical research programs, investigating relevant immunological mechanisms underlying Type I diabetes, asthma and breast cancer.
- D. Desai, S. Harbers, L. Colonna, M. Downie, A. Bergtold, S. Jung, and R. Clynes Fc Receptor IIB on Dendritic Cells Enforces Peripheral Tolerance by Inhibiting Effector T Cell Responses J Immunol 178: 6217-6226 (2007) . PMID: 17475849
- S. Harbers, A. Crocker, G. Catalano, V. D’Agati, S. Jung, D. D. Desai, and R. Clynes Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance J. Clin. Invest. 117: 1361-1369 (2007). PMCID: PMC1849985
- L. He, A. Crocker, J. Lee, J. Ramirez, X. Wang, L.Vitale, T. O’Neill, C. Petromilli, H. Zhang, J. Lopez, D. Rohrer, T. Keler, and R. Clynes Antigenic Targeting of the Human Mannose Receptor Induces Tumor Immunity J Immunol 178: 6259-6267 (2007). PMID: 17475854
- C. Taylor, D. Hershman, N. Shah, N. Suciu-Foca, M. Pegram, K. L. Knutson, and R. Clynes Augmented HER-2–Specific Immunity during Treatment with Trastuzumab and Chemotherapy, Clin Cancer Res 13: 5133-43 (2007). PMID: 17785568
- Clynes R., Protective mechanisms of IVIG., Curr Opin Immunol. (6):646-51 (2007) PMID: 18032008
- Moser B, Desai DD, Downie MP, Chen Y, Yan SF, Herold K, Schmidt AM, Clynes R., Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo .J Immunol. 79(12):8051-8 (2007) PMID: 18056345
- Liang, B., Vignali, D. and R. Clynes, Regulatory T cells inhibit dendritic cells by LAG-3 engagement of MHC Class II, J Immunol. 180(9):5916-26 (2008). PMID: 18424711
- Flores M, Desai DD, Downie M, Liang B, Reilly MP, McKenzie SE, Clynes R. Dominant expression of the inhibitory FcgammaRIIB prevents antigen presentation by murine plasmacytoid dendritic cells. J Immunol,183:7129-39 (2009) PMID: 19917701
- Clynes, R B cell therapy is beta-tested: Rituximab puts a pause on beta cell destruction, Islets, 2:2 (2010)
- Colonna, L., R. Clynes, Targeting Syk in Type I diabetes, J Immunol,(2010) PMID: 20601600