Subramaniam Sriram, M.B.B.S.


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Faculty Appointments
Professor of Neurology William C. Weaver III Chair in NeurologyProfessor of Pathology, Microbiology and Immunology
M.B.B.S., Medicine, Madras University, Madras, India
Office Address
2201 Capers Ave. #1222
Vanderbilt Stallworth Rehabilitation Hospital
USA, TN 37212
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. .
Research Keywords
Mechanism of CNS demyelination
Sriram S, Steiner I. Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis. Ann. Neurol. 2005 Dec; 58(6): 939-45. PMID: 16315280, DOI: 10.1002/ana.20743, ISSN: 0364-5134.

Deng X, Ljunggren-Rose A, Maas K, Sriram S. Defective ATM-p53-mediated apoptotic pathway in multiple sclerosis. Ann. Neurol. 2005 Oct; 58(4): 577-84. PMID: 16178012, DOI: 10.1002/ana.20600, ISSN: 0364-5134.

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 [print-electronic]. 2005 Oct 10/1/2005; 192(7): 1219-28. PMID: 16136465, PII: JID34005, DOI: 10.1086/431518, ISSN: 0022-1899.

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. 2005 Jul 7/15/2005; 234(1-2): 87-91. PMID: 15935383, PII: S0022-510X(05)00123-1, DOI: 10.1016/j.jns.2005.03.042, ISSN: 0022-510X.

Deng X, Sriram S. Role of microglia in multiple sclerosis. Curr Neurol Neurosci Rep. 2005 May; 5(3): 239-44. PMID: 15865890, ISSN: 1528-4042.

Natarajan C, Sriram S, Muthian G, Bright JJ. Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of microglia. Glia. 2004 Jan 1/15/2004; 45(2): 188-96. PMID: 14730712, DOI: 10.1002/glia.10316, ISSN: 0894-1491.

Stratton CW, Sriram S. Association of Chlamydia pneumoniae with central nervous system disease. Microbes Infect. 2003 Nov; 5(13): 1249-53. PMID: 14623021, PII: S1286457903002363, ISSN: 1286-4579.

Du C, Yao SY, Ljunggren-Rose A, Sriram S. Chlamydia pneumoniae infection of the central nervous system worsens experimental allergic encephalitis. J. Exp. Med. 2002 Dec 12/16/2002; 196(12): 1639-44. PMID: 12486106, PMCID: PMC2196067, ISSN: 0022-1007.

Sriram S, Yao SY, Stratton C, Calabresi P, Mitchell W, Ikejima H, Yamamoto Y. Comparative study of the presence of Chlamydia pneumoniae in cerebrospinal fluid of Patients with clinically definite and monosymptomatic multiple sclerosis. Clin. Diagn. Lab. Immunol. 2002 Nov; 9(6): 1332-7. PMID: 12414770, PMCID: PMC130123, ISSN: 1071-412X.

Kaufman M, Gaydos CA, Sriram S, Boman J, Tondella ML, Norton HJ. Is Chlamydia pneumoniae found in spinal fluid samples from multiple sclerosis patients? Conflicting results. Mult. Scler. 2002 Aug; 8(4): 289-94. PMID: 12166498, ISSN: 1352-4585.

Du C, Sriram S. Increased severity of experimental allergic encephalomyelitis in lyn-/- mice in the absence of elevated proinflammatory cytokine response in the central nervous system. J. Immunol. 2002 Mar 3/15/2002; 168(6): 3105-12. PMID: 11884485, ISSN: 0022-1767.

Singh AK, Wilson MT, Hong S, Olivares-Villagómez D, Du C, Stanic AK, Joyce S, Sriram S, Koezuka Y, Van Kaer L. Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J. Exp. Med. 2001 Dec 12/17/2001; 194(12): 1801-11. PMID: 11748281, PMCID: PMC2193577, ISSN: 0022-1007.

Du C, Khalil MW, Sriram S. Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice. J. Immunol. 2001 Dec 12/15/2001; 167(12): 7094-101. PMID: 11739531, ISSN: 0022-1767.

Du C, Guan Q, Khalil MW, Sriram S. Stimulation of Th2 response by high doses of dehydroepiandrosterone in KLH-primed splenocytes. Exp. Biol. Med. (Maywood). 2001 Dec; 226(11): 1051-60. PMID: 11743142, ISSN: 1535-3702.

Yucesan C, Sriram S. Chlamydia pneumoniae infection of the central nervous system. Curr. Opin. Neurol. 2001 Jun; 14(3): 355-9. PMID: 11371760, ISSN: 1350-7540.

Yao SY, Stratton CW, Mitchell WM, Sriram S. CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens. Neurology. 2001 May 5/8/2001; 56(9): 1168-76. PMID: 11342681, ISSN: 0028-3878.

Yao SY, Ljunggren-Rose A, Stratton CW, Mitchell WM, 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. 2001 Mar; 21(3): 137-46. PMID: 11331036, DOI: 10.1089/107999001750133131, ISSN: 1079-9907.

Du C, Bright JJ, 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. 2001 Mar 3/1/2001; 114(1-2): 69-79. PMID: 11240017, PII: S0165572800004343, ISSN: 0165-5728.

Bright JJ, Sriram S. Immunotherapy of inflammatory demyelinating diseases of the central nervous system. Immunol. Res. 2001; 23(2-3): 245-52. PMID: 11444389, PII: IR:23:2-3:245, DOI: 10.1385/IR:23:2-3:245, ISSN: 0257-277X.

Moses H, Sriram S. An infectious basis for multiple sclerosis: perspectives on the role of Chlamydia pneumoniae and other agents. BioDrugs. 2001; 15(3): 199-206. PMID: 11437685, PII: 150306, ISSN: 1173-8804.

Du C, Cooper JC, Klaus SJ, Sriram S. Amelioration of CR-EAE with lisofylline: effects on mRNA levels of IL-12 and IFN-gamma in the CNS. J. Neuroimmunol. 2000 Oct 10/2/2000; 110(1-2): 13-9. PMID: 11024530, PII: S0165-5728(00)00348-9, ISSN: 0165-5728.

Du C, Sriram S. Induction of interleukin-12/p40 by superantigens in macrophages is mediated by activation of nuclear factor-kappaB. Cell. Immunol. 2000 Jan 1/10/2000; 199(1): 50-7. PMID: 10675275, PII: S0008-8749(99)91595-2, DOI: 10.1006/cimm.1999.1595, ISSN: 0008-8749.

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

Sriram S, Stratton CW, Yao S, Tharp A, Ding L, Bannan JD, Mitchell WM. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann. Neurol. 1999 Jul; 46(1): 6-14. PMID: 10401775, ISSN: 0364-5134.

Bright JJ, 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. 1999 May 5/15/1999; 162(10): 6255-62. PMID: 10229872, ISSN: 0022-1767.

Bright JJ, Xin Z, Sriram S. Superantigens augment antigen-specific Th1 responses by inducing IL-12 production in macrophages. J. Leukoc. Biol. 1999 May; 65(5): 665-70. PMID: 10331496, ISSN: 0741-5400.

Bright JJ, Rodriguez M, Sriram S. Differential influence of interleukin-12 in the pathogenesis of autoimmune and virus-induced central nervous system demyelination. J. Virol. 1999 Feb; 73(2): 1637-9. PMID: 9882371, PMCID: PMC103990, ISSN: 0022-538X.

Moses H, Jr and SriramS. Interferon beta and the cytokine trail: where are we going?. Neurology. 1999; 52((9)): 1729-30.

Bright JJ, Du C, Coon M, Sriram S, Klaus SJ. 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. 1998 Dec 12/15/1998; 161(12): 7015-22. PMID: 9862738, ISSN: 0022-1767.

Bright JJ, Sriram S. TGF-beta inhibits IL-12-induced activation of Jak-STAT pathway in T lymphocytes. J. Immunol. 1998 Aug 8/15/1998; 161(4): 1772-7. PMID: 9712043, ISSN: 0022-1767.

Xin Z, Sriram S. Vasoactive intestinal peptide inhibits IL-12 and nitric oxide production in murine macrophages. J. Neuroimmunol. 1998 Aug 8/14/1998; 89(1-2): 206-12. PMID: 9726844, ISSN: 0165-5728.

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. 1998 Jul; 64(1): 92-7. PMID: 9665281, ISSN: 0741-5400.

Bright JJ, Musuro BF, Du C, Sriram S. Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic encephalitis. J. Neuroimmunol. 1998 Feb; 82(1): 22-30. PMID: 9526842, PII: S0165-5728(97)00184-7, ISSN: 0165-5728.

Sriram S, Mitchell W, Stratton C. Multiple sclerosis associated with Chlamydia pneumoniae infection of the CNS. Neurology. 1998 Feb; 50(2): 571-2. PMID: 9484408, ISSN: 0028-3878.

Bright JJ, Kerr LD, Sriram S. TGF-beta inhibits IL-2-induced tyrosine phosphorylation and activation of Jak-1 and Stat 5 in T lymphocytes. J. Immunol. 1997 Jul 7/1/1997; 159(1): 175-83. PMID: 9200453, ISSN: 0022-1767.

Sriram S, Rodriguez M. Indictment of the microglia as the villain in multiple sclerosis. Neurology. 1997 Feb; 48(2): 464-70. PMID: 9040740, ISSN: 0028-3878.

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. 1997; 75: 204-9.

Lodge PA, Sriram S. Regulation of microglial activation by TGF-beta, IL-10, and CSF-1. J. Leukoc. Biol. 1996 Oct; 60(4): 502-8. PMID: 8864135, ISSN: 0741-5400.

Bright JJ, Topham DJ, Nag B, Lodge PA, Sriram S. Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE. J. Neuroimmunol. 1996 Jul; 67(2): 119-24. PMID: 8765334, PII: S0165572896000574, ISSN: 0165-5728.

Lodge PA, Johnson C, Sriram S. Frequency of MBP and MBP peptide-reactive T cells in the HPRT mutant T-cell population of MS patients. Neurology. 1996 May; 46(5): 1410-5. PMID: 8628491, ISSN: 0028-3878.

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. 1996; 170: 25-33.

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. 1996; 44: 1633-8.

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

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. 1995; 155: 325-32.

Lodge PA, 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. 1994 Nov; 36(5): 734-40. PMID: 7526775, DOI: 10.1002/ana.410360508, ISSN: 0364-5134.

Topham DJ, 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. 1994 Aug 8/16/1994; 91(17): 8005-9. PMID: 8058747, PMCID: PMC44533, ISSN: 0027-8424.

Sriram S. Longitudinal study of frequency of HPRT mutant T cells in patients with multiple sclerosis. Neurology. 1994 Feb; 44(2): 311-5. PMID: 8309581, ISSN: 0028-3878.

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. 1994; 94: 105-9.

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

Sharma K, Fries T, Sriram S and Bradley WG. EB virus associated plexopathy. Neurology. 1993; 43: 2550-4.

Racke M, Sriram S, Carlino J, Canellal B, Raine CS and McFarlin DE. Long term treatment of CR-EAE with TGF_2. J Neuroimmunol. 1993; 46: 175-84.

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

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. 1992; 585: 229-36.

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

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. 1992; 141: 485-95.

Johns LJ, Flanders K, Ranges G and Sriram S. Successful therapy of experimental allergic encephalitis with TG_1. J Immunol. 1991; 147: 1742-6.

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. 1991; 65: 3238-45.

Available Postdoctoral Position Details
Posted: 5/27/2008
A two year post doctoral position is available in the laboratory of Neuroimmunology. The field of study will be to examine the role of DNA damage pathway in human demyelinating disorders that are thougt to have either an autoimmune or infectious basis. The study will examine the role of ATM-P53 pathway and the ATR-p53 pathway in the regulation of immune function in human blood lymphocytes, spinal fluid and from CNS tissue obtained from surgical specimens. The position will require familiarity working with human samples including blood and spinal fluid and brain tissue. Candidates should have a strong background in biochemistry, neurochemistry and immunology. Only candidates who have strong academic grounding and have completed their PhD within the last two years need apply.