.

Department of Pathology, Microbiology, and Immunology

 

 

  Subramaniam Sriram, M.B., B.S.

 

 

Professor

Dept of Neurology

Dept of Pathology, Microbiology and Immunology

William C. Weaver III Professor of Neurology

 

 

Contact Information

 

 

Office Location:
Stallworth Rehab Hospital Rm 1222
Phone: 615-936-4042

E-mail:  subramaniam.sriram@vanderbilt.edu/

 

Lab URL:

http://www.mc.vanderbilt.edu/neurology/neuroimmunology.htm

 

Campus Mail address:

Neurology

Stallworth Rehab 1222 (8500)

 

Mailing Address:
Vanderbilt University School of Medicine
MS Research Laboratory

2201 Children’s Way, St. 1222
Nashville, TN 37212

 

 

 

Education

 

 

Postdoctoral Fellow, Stanford University, Stanford, California
M.D., B.S., University of Madras, Madras, India

 

 

Research Keywords

 

 

Cytokines, Microglia, Autoimmune Diseases, Neuroimmunology

 

 

Research Description

 

 

The neuroimmunology research program is focused on understanding the mechanism of inflammatory demyelination in the central nervous system (CNS). The underpinnings of CNS demyelination appear to depend on the close interactions between T cells that are targeted to CNS antigens and the activation and secretion of proinflammatory cytokines made by microglial cells. In particular, we are interested in defining how the immunoinhibitory cytokines, TGFb and IL-10, affect T cell/microglial activation. Our efforts are currently designed to address the signal transduction pathways that are involved in cytokine signaling and the mechanism by which the signals are altered.

Our laboratory also uses an autoimmune model of CNS demyelination experimental allergic encephalitis to develop therapeutic strategies that may be eventually applicable to treatment of human demyelinating disease such as multiple sclerosis. These include the use of pro-inflammatory cytokine antagonists, cytokine receptor antagonists and compounds that interfere with signal transduction pathways. .

 

 

Publications

 

 

Deng, X, Ljunggren-Rose, A, Maas, K, Sriram, S. Defective ATM-p53-mediated apoptotic pathway in multiple sclerosis. Ann Neurol, 58(4), 577-84, 2005

Sriram, S, Ljunggren-Rose, A, Yao, SY, Whetsell, WO. Detection of chlamydial bodies and antigens in the central nervous system of patients with multiple sclerosis. J Infect Dis, 192(7), 1219-28, 2005

Sriram, S, Steiner, I. Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis. Ann Neurol, 58(6), 939-45, 2005

Deng, X, Sriram, S. Role of microglia in multiple sclerosis. Curr Neurol Neurosci Rep, 5(3), 239-44, 2005

Sriram, S, Yao, SY, Stratton, C, Moses, H, Narayana, PA, Wolinsky, JS. Pilot study to examine the effect of antibiotic therapy on MRI outcomes in RRMS. J Neurol Sci, 234(1-2), 87-91, 2005

Natarajan, Chandramohan, Sriram, Subramaniam, Muthian, Gladson, Bright, John J. Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of microglia. Glia, 45(2), 188-96, 2004

Stratton, Charles W, Sriram, Subramaniam. Association of Chlamydia pneumoniae with central nervous system disease. Microbes Infect, 5(13), 1249-53, 2003

Du, Caigan, Yao, Song-Yi, Ljunggren-Rose, Asa, Sriram, Subramaniam. Chlamydia pneumoniae infection of the central nervous system worsens experimental allergic encephalitis. J Exp Med, 196(12), 1639-44, 2002

Sriram, Subramaniam, Yao, Song-Yi, Stratton, Charles, Calabresi, Peter, Mitchell, William, Ikejima, Hideaki, Yamamoto, Yoshimasa. Comparative study of the presence of Chlamydia pneumoniae in cerebrospinal fluid of Patients with clinically definite and monosymptomatic multiple sclerosis. Clin Diagn Lab Immunol, 9(6), 1332-7, 2002

Kaufman, M, Gaydos, C A, Sriram, S, Boman, J, Tondella, M L, Norton, H J. Is Chiamydia pneumoniae found in spinal fluid samples from multiple sclerosis patients? Conflicting results. Mult Scler, 8(4), 289-94, 2002

Du, Caigan, Sriram, Subramaniam. Increased severity of experimental allergic encephalomyelitis in lyn-/- mice in the absence of elevated proinflammatory cytokine response in the central nervous system. J Immunol, 168(6), 3105-12, 2002

Moses, H, Sriram, S. An infectious basis for multiple sclerosis: perspectives on the role of Chlamydia pneumoniae and other agents. BioDrugs, 15(3), 199-206, 2001

Du, C, Bright, J J, Sriram, S. Inhibition of CD40 signaling pathway by tyrphostin A1 reduces secretion of IL-12 in macrophage, Th1 cell development and experimental allergic encephalomyelitis in SJL/J mice. J Neuroimmunol, 114(1-2), 69-79, 2001

Yao, S Y, Ljunggren-Rose, A, Stratton, C W, Mitchell, W M, Sriram, S. Regulation by IFN-beta of inducible nitric oxide synthase and interleukin-12/p40 in murine macrophages cultured in the presence of Chlamydia pneumoniae antigens. J Interferon Cytokine Res, 21(3), 137-46, 2001

Yao, S Y, Stratton, C W, Mitchell, W M, Sriram, S. CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens. Neurology, 56(9), 1168-76, 2001

Yucesan, C, Sriram, S. Chlamydia pneumoniae infection of the central nervous system. Curr Opin Neurol, 14(3), 355-9, 2001

Bright, J J, Sriram, S. Immunotherapy of inflammatory demyelinating diseases of the central nervous system. Immunol Res, 23(2-3), 245-52, 2001

Du, C, Khalil, M W, Sriram, S. Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice. J Immunol, 167(12), 7094-101, 2001

Du, C, Guan, Q, Khalil, M W, Sriram, S. Stimulation of Th2 response by high doses of dehydroepiandrosterone in KLH-primed splenocytes. Exp Biol Med (Maywood), 226(11), 1051-60, 2001

Singh, A K, Wilson, M T, Hong, S, Olivares-Villag??mez, D, Du, C, Stanic, A K, Joyce, S, Sriram, S, Koezuka, Y, Van Kaer, L. Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J Exp Med, 194(12), 1801-11, 2001

Du, C, Sriram, S. Induction of interleukin-12/p40 by superantigens in macrophages is mediated by activation of nuclear factor-kappaB. Cell Immunol, 199(1), 50-7, 2000

Stratton CW, Mitchell WM, Sriram S. Does Chlamydia pneumoniae play a role in the pathogenesis of multiple sclerosis? . J Med Microbiol, 49(1), 1-3, 2000

Du, C, Cooper, J C, Klaus, S J, Sriram, S. Amelioration of CR-EAE with lisofylline: effects on mRNA levels of IL-12 and IFN-gamma in the CNS. J Neuroimmunol, 110(1-2), 13-9, 2000

Sriram, S, Stratton, C W, Yao, S, Tharp, A, Ding, L, Bannan, J D, Mitchell, W M. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann Neurol, 46(1), 6-14, 1999

Bright, J J, Xin, Z, Sriram, S. Superantigens augment antigen-specific Th1 responses by inducing IL-12 production in macrophages. J Leukoc Biol, 65(5), 665-70, 1999

Bright, J J, Du, C, Sriram, S. Tyrphostin B42 inhibits IL-12-induced tyrosine phosphorylation and activation of Janus kinase-2 and prevents experimental allergic encephalomyelitis. J Immunol, 162(10), 6255-62, 1999

Bright, J J, Rodriguez, M, Sriram, S. Differential influence of interleukin-12 in the pathogenesis of autoimmune and virus-induced central nervous system demyelination. J Virol, 73(2), 1637-9, 1999

Moses H, Jr and SriramS. Interferon beta and the cytokine trail: where are we going?. Neurology , 52(9), 1729-1730, 1999

Bright, J J, Du, C, Coon, M, Sriram, S, Klaus, S J. Prevention of experimental allergic encephalomyelitis via inhibition of IL-12 signaling and IL-12-mediated Th1 differentiation: an effect of the novel anti-inflammatory drug lisofylline. J Immunol, 161(12), 7015-22, 1998

Bright, J J, Sriram, S. TGF-beta inhibits IL-12-induced activation of Jak-STAT pathway in T lymphocytes. J Immunol, 161(4), 1772-7, 1998

Du, C, Sriram, S. Mechanism of inhibition of LPS-induced IL-12p40 production by IL-10 and TGF-beta in ANA-1 cells. J Leukoc Biol, 64(1), 92-7, 1998

Bright, J J, Musuro, B F, Du, C, Sriram, S. Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic encephalitis. J Neuroimmunol, 82(1), 22-30, 1998

Sriram, S, Mitchell, W, Stratton, C. Multiple sclerosis associated with Chlamydia pneumoniae infection of the CNS. Neurology, 50(2), 571-2, 1998

Xin, Z, Sriram, S. Vasoactive intestinal peptide inhibits IL-12 and nitric oxide production in murine macrophages. J Neuroimmunol, 89(1-2), 206-12, 1998

Miller DJ, Bright JJ, Sriram S and Rodriguez M. Successful treatment of established relapsing experimental autoimmune encephalomyelitis in mice with a monoclonal natural autoantibody. J Neuroimmunol, 75, 204-209, 1997

Sriram, S, Rodriguez, M. Indictment of the microglia as the villain in multiple sclerosis. Neurology, 48(2), 464-70, 1997

Bright, J J, Kerr, L D, Sriram, S. TGF-beta inhibits IL-2-induced tyrosine phosphorylation and activation of Jak-1 and Stat 5 in T lymphocytes. J Immunol, 159(1), 175-83, 1997

Lodge, P A, Sriram, S. Regulation of microglial activation by TGF-beta, IL-10, and CSF-1. J Leukoc Biol, 60(4), 502-8, 1996

Bright, J J, Topham, D J, Nag, B, Lodge, P A, Sriram, S. Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE. J Neuroimmunol, 67(2), 119-24, 1996

Broad SA, Marshall GD, Henninger EM, Sriram S, Khan M and Wolinsky JS. Interferon Beta treatment decreases tumor necrosis factor alpha and increases IL-6 production in MS patients. Neurology, 44, 1633-1638, 1996

Nag B, Kendrick T, Arimilli S, Yu CT and Sriram S. Soluble MHC II-peptide complexes induce antigen-specific apoptosis in T cells. Cell Immunol, 170, 25-33, 1996

Lodge, P A, Johnson, C, Sriram, S. Frequency of MBP and MBP peptide-reactive T cells in the HPRT mutant T-cell population of MS patients. Neurology, 46(5), 1410-5, 1996

Fabry Z, Topham DJ, Fee D, Herlein J, Carlino J, Hart MN and Sriram S. TGF_ decreases the migration of lymphocytes across capillary endothelium in vitro and homing of cells into brain in vivo. J Immunol, 155, 325-332, 1995

Owens T and Sriram S. The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis (Review). Neurol Clin NA, 13(11), 51-73, 1995

, 1995

Lodge, P A, Allegretta, M, Steinman, L, Sriram, S. Myelin basic protein peptide specificity and T-cell receptor gene usage of HPRT mutant T-cell clones in patients with multiple sclerosis. Ann Neurol, 36(5), 734-40, 1994

Topham, D J, Nag, B, Arimilli, S, Sriram, S. A synthetic peptide from the third hypervariable region of major histocompatibility complex class II beta chain as a vaccine for treatment of experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A, 91(17), 8005-9, 1994

Sriram, S. Longitudinal study of frequency of HPRT mutant T cells in patients with multiple sclerosis. Neurology, 44(2), 311-5, 1994

Sriram S and Owens T . Neuro-immunology . Neurology in Clinical Practice, 1994

Allegretta M, Albertini RA, Howell MD, Martin R, McFarland HF, Brostoff S, Sriram S and Steinman L. Homologies between TcR junction sequences unique to MS and T cells mediating EAE. J Clin Invest , 94, 105-109, 1994

Johns LD and Sriram S. Neutralizing antibody to TGF_1 enhances the clinical severity of EAE. J Neuroimmunol, 47, 1-9, 1993

Racke M, Sriram S, Carlino J, Canellal B, Raine CS and McFarlin DE. Long term treatment of CR-EAE with TGF_2. J Neuroimmunol, 46, 175-184, 1993

Sharma K, Fries T, Sriram S and Bradley WG. EB virus associated plexopathy. Neurology, 43, 2550-2554, 1993

Su XM and Sriram S. Analysis of TCR V_ gene usage of MBP p91-103 reactive T cell clones in SJL mice; Lack of evidence for V gene hypothesis. Cell Immunol, 141, 485-495, 1992

Sriram S, Pendlebury W, Johns L and Flanders K. Identification and localization of TGF__in brains of patients with Multiple Sclerosis. Neurology, 41, 219, 1992

Johns LD, Babcock G, Green D, Freedman M, Sriram S and Ransohoff R. TGF__differentially regulates proliferation and MHC class II antigen expression in forebrain and brainstem astrocytes primary cultures. Brain Res, 585, 229-236, 1992

Topham DJ, Adekunle A, Shenoy M, Craighead JE and Sriram S. The indirect role of T cells in the development of polioencephalitis and encephalomyelitis induced by EMC virus. J Virol, 65, 3238-3245, 1991

Johns LJ, Flanders K, Ranges G and Sriram S. Successful therapy of experimental allergic encephalitis with TG_1. J Immunol, 147, 1742-1746, 1991