MARTES 22 DE MARZO, 17 HRS

AUDITORIO DEL HOSPITAL DE ONCOLOGIA, CENTRO MEDICO XXI

Chander Raman, Ph.D.
Associate Professor
Department of Medicine

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Research Focus:  Lymphocyte activation, immune
tolerance and autoimmunity

Lab Research Focus

The major research interest of my laboratory is to elucidate the molecular mechanism/s by which lymphocyte co-receptors regulate lymphocyte activation and selection with focus on development of autoimmunity.
Currently, our studies focus on the co-receptor CD5 that is expressed on all T cells and a subset of B cells, also described as B1a or CD5+ B cells. The B1a B cell B cell population is the major B cell population responsible for the neonatal repertoire and the natural antibody repertoire in human and mice. CD5 expressing B cell are also the major B cell population from which most B cell leukemias develop. In many autoimmune diseases, including rheumatoid arthritis and Sjögren's syndrome, CD5 expressing B cells are expanded and are responsible for the production of pathogenic autoantibodies. Using CD5-transgenic and CD5-knock out mice, bred into experimentally derived murine autoimmunity animal models, we have now demonstrated that signals transduced by CD5 have a direct effect on B cell selection and development of autoimmunity. Parallel studies from other laboratories and ours also show that CD5 is a key regulator of T cell selection and differentiation. The goal now is to elucidate the molecular mechanisms by which CD5 is able to exert its activity in T and B cells. To address these questions we are developing animal models that express mutant forms of CD5 as a transgene. These mutant CD5-transgenic mice will be used as a source of normal T and B cells to define signal transduction pathways recruited by CD5. Additionally we are also developing models that will enable us to transduce primary B and T cells in vivo and ex vivo using a virus-mediated gene transfer approach.

We predict that by these approaches we will be elucidate molecular mechanisms that are important in regulating lymphocyte selection, activation and differentiation and provide novel approaches to control and treat autoimmune diseases and neoplasias.

Publicaciones recientes.

T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis.Axtell RC, de Jong BA, Boniface K, van der Voort LF, Bhat R, De Sarno P, Naves R, Han M, Zhong F, Castellanos JG, Mair R, Christakos A, Kolkowitz I, Katz L, Killestein J, Polman CH, de Waal Malefyt R, Steinman L, Raman C.Nat Med. 2010 Apr;16(4):406-12. Epub 2010 Mar 28.

Increased antigen responsiveness of naive CD8 T cells exposed to IL-7 and IL-21 is associated with decreased CD5 expression. Gagnon J, Chen XL, Forand-Boulerice M, Leblanc C, Raman C, Ramanathan S, Ilangumaran S. Immunol Cell Biol. 2010 May-Jun;88(4):451-60. Epub 2010 Jan 12.PMID: 20065997

Marginal zone precursor B cells as cellular agents for type I IFN-promoted antigen transport in autoimmunity.

Wang JH, Li J, Wu Q, Yang P, Pawar RD, Xie S, Timares L, Raman C, Chaplin DD, Lu L, Mountz JD, Hsu HC.J Immunol. 2010 Jan 1;184(1):442-51. Epub 2009 Nov 30.

Increased numbers of thymic and peripheral CD4+ CD25+Foxp3+ cells in the absence of CD5 signaling.Ordoñez-Rueda D, Lozano F, Sarukhan A, Raman C, Garcia-Zepeda EA, Soldevila G.Eur J Immunol. 2009 Aug;39(8):2233-47.PMID: 19609976

CD5 plays an inhibitory role in the suppressive function of murine CD4(+) CD25(+) T(reg) cells. Dasu T, Qualls JE, Tuna H, Raman C, Cohen DA, Bondada S.Immunol Lett. 2008 Aug 15;119(1-2):103-13. Epub 2008 Jun 23.PMID: 18573278

CD5-CK2 binding/activation-deficient mice are resistant to experimental autoimmune encephalomyelitis: protection is associated with diminished populations of IL-17-expressing T cells in the central nervous system. Axtell RC, Xu L, Barnum SR, Raman C.J Immunol. 2006 Dec 15;177(12):8542-9.PMID: 17142752

Cutting edge: critical role for CD5 in experimental autoimmune encephalomyelitis: inhibition of engagement reverses disease in mice. Axtell RC, Webb MS, Barnum SR, Raman C. J Immunol. 2004 Sep 1;173(5):2928-32.

Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas(lpr) mice from autoimmune disease. Kevil CG, Hicks MJ, He X, Zhang J, Ballantyne CM, Raman C, Schoeb TR, Bullard DC.

Am J Pathol. 2004 Aug;165(2):609-16.

CD5, an important regulator of lymphocyte selection and immune tolerance. Raman C. Immunol Res. 2002;26(1-3):255-63. Review.PMID: 12403363

AP2 adaptor complex-dependent internalization of CD5: differential regulation in T and B cells. Lu X, Axtell RC, Collawn JF, Gibson A, Justement LB, Raman C.J Immunol. 2002 Jun 1;168(11):5612-20.PMID: 12023358

CD45 function is regulated by an acidic 19-amino acid insert in domain II that serves as a binding and phosphoacceptor site for casein kinase 2. Greer SF, Wang Y, Raman C, Justement LB. J Immunol. 2001 Jun 15;166(12):7208-18.PMID: 11390469