Assistant Professor of Neurology
Dr. Bright earned his B.Sc. (1980), M.Sc. (1985) and M.Phil. (1986) degrees in Zoology while at Madurai Kamaraj University in Tamil Nadu, India. In 1993, he received a Ph.D. in Biochemistry from University of Kerala in Trivandrum, India. Following two years as a post-doctoral fellow at the Centre for Cellular and Molecular Biology in Hyderabad, India, Bright immigrated to America and spent two years as a post-doctoral fellow in the Neurology department at Vanderbilt.
From 1996-98, he worked as a Research Associate in the Neurology department, supported by an advanced postdoctoral fellowship from the National Multiple Sclerosis Society. From 1998-99 Bright served on the faculty as Instructor of Neurology, and in 1999 he was made Assistant Professor of Neurology.
Bright is also an assistant professor of Pharmacology and a member of the American Association of Immunologists and the American Association for Cancer Research.
Bright’s laboratory investigates the molecular mechanisms in the regulation of neuro-immune signaling relevant to autoimmune diseases, cancer biology and immunology and stem cell biology of the brain. We use a combination of state-of-the-art cell biology, biochemistry, immunology and molecular biology techniques in vitro and in relevant transgenic and knockout mouse in vivo. Research in Bright’s laboratory has been funded by grants from National Institutes of Health and National Multiple Sclerosis Society.
The immune system has evolved to discriminate self from non-self antigens thereby protecting the host from microbial pathogens and malignant tumor. Nevertheless, a breakdown in this fundamental immunoregulatory process often results in the pathogenesis of chronic infectious diseases, malignant tumors and organ-specific autoimmune diseases. The CD4+ T helper 1 cells play critical roles in mediating protection against infection and cancer or the pathogenesis of autoimmune diseases. We investigate the role of JAK-STAT and other neuro-immune signaling pathways in the pathogenesis of inflammatory autoimmune diseases. Using the EAE model of multiple sclerosis, we study the molecular mechanisms in the regulation of JAK-STAT signaling pathways by nuclear receptor transcription factors including, PPARgamma, estrogen receptor and vitamin D receptor in Th1 cell-mediated autoimmune diseases. We also examine the use and mode of action of nutraceuticals and phytochemicalson the treatment of autoimmune diseases.
Stem cell biology
The spontaneous recovery of CNS disorders such as multiple sclerosis, spinal cord injury, stroke and trauma is hindered by limited ability of the vertebrate CNS to regenerate lost cells, replace damaged myelin and re-establish the functional neuronal connections. Stem cells with self-renewal and multilineage differentiation properties, have the potential to replace or repair damaged tissue. We investigate the presence of neural progenitor cells in adult brain and their ability to differentiate into oligodendrocyte, astrocyte and neuron. We also study the neuro-glial differentiation of embryonic stem cells in culture. We examine the specific signaling pathways and transcription factors associated with the proliferation and neuro-glial differentiation of adult and embryonic stem cells. We determine the mechanisms in the engraftment, proliferation, migration, and neuro-glia differentiation of stem cells in the brain. We test the use of nuclear receptors in the regulation of neuro-glial differentiation and their use in stem cell t transplantation therapy for multiple sclerosis and other neurodegenerative diseases.
Cancer biology and immunology
The tight regulation of growth factor-dependent cell proliferation, cell survival and programmed cell death are important phenomenon in the maintenance of homeostasis in animals. The spontaneous or microbial pathogen-induced changes in cells can lead to dysregulated growth and resistance to apoptosis, resulting in the pathogenesis of malignant tumors. We investigate the constitutive activation of growth signaling pathways and their contribution to the dysregulated growth and resistance to apoptosis in HTLV-1 transformed T cell leukemia and glioma. We study the regulation of constitutively active JAK-STAT signaling pathway by PPARgamma agonists and nutraceuticals in leukemia and glioma. We also determine the mechanisms in the induction of protective immunity to cancer in animal models.
PERSONNEL IN BRIGHT’S LABORATORY
Gladson Muthian, Ph.D. is a postdoctoral fellow in Bright’s laboratory, who works on determining the mechanisms in the regulation of growth, immune and inflammatory signaling pathways by PPAR and ER agonists in the CNS.
Himanshu P. Raikwar, Ph.D. is a postdoctoral fellow in Bright’s laboratory, who works on defining the role of PPAR in the regulation of CNS inflammation and demyelination.
Rajasingh Johnson, Ph.D. is a postdoctoral fellow in Bright’s laboratory, who works on examining the mechanisms in the regulation of JAK-STAT pathway in growth and differentiation of immune, stem and cancer cells.
Caroline Johnson, M.Sc. is a research assistant in Bright’s laboratory, who works on culture and maintenance of immune and stem cells.
Muthian, G., and Bright, J. J. 2003. Quercetin ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte. J. Clin. Immunol . 24: 541-551.
Bright, J. J., 2004. Targeting autoimmune diseases through nutraceuticals. Nutrition. 20: 39-43.
Natarajan, C., Muthian, G., Barak, Y., Evans, R. M., and Bright, J. J. 2003. Peroxisome proliferator-activated receptor-gamma deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis. J. Immunol. 171, 5743-5750.
Natarajan, C., Sriram, S., Muthian, G., and Bright, J. J. 2004. Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of microglia. GLIA. 45: 188-196.
Natarajan, C., and Bright, J. J. 2002. PPAR-gamma agonists inhibit EAE by blocking IL-12 production, IL-12 signaling and Th1 differentiation. Gene. Immunity. 3: 59-70.
Natarajan, C., and Bright, J. J. 2002. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J. Immunol. 169, 6506-6513.
Bright, J. J., and Sriram, S. 2001. Immunotherapy of inflammatory demyelinating diseases of the central nervous system. Immunol. Res. 23: 245-52.
Du, C., Bright, J. J. and Sriram, S. 2001. 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: 69-79.
Bright, J. J., Xin, Z. and Sriram, S. 1999. Superantigens augment antigen specific Th1 responses by inducing IL-12 production from macrophages. J. Leuc. Biol. 65: 665-670.
Bright, J. J., Rodriguez, M. and Sriram, S. 1999. Differential influence of IL-12 in the pathogenesis of autoimmune and virus induced CNS demyelination. J. Virol. 73: 1637-1639.
Bright, J. J. and Sriram, S. 1999. Tyrphostin B42 inhibits IL-12-induced tyrosine phosphorylation and activation of JAK-2 kinase and prevent experimental allergic encephalomyelitis. J. Immunol. 162: 6255-6262.
Bright, J. J., Du, C., Coon, M., Sriram, S. and Klaus, S. J. 1998. 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: 7015-7022.
Bright, J. J. and Sriram, S. 1998. TGF-b inhibits IL-12-induced activation of Jak-STAT pathway in T lymphocytes. J. Immunol. 161: 1772-1777.
Bright, J. J., Musuro, B. F., Du, C. and Sriram, S. 1998. Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic encephalomyelitis. J. Neuroimmunol. 82: 22 30.
Bright, J.J., Kerr, L. D. and Sriram, S. 1997. TGF-b inhibits IL-2-induced phosphorylation and activation of Jak-1 and Stat5 in T lymphocytes. J. Immunol. 159: 175-183.
Miller, D. J., Bright, J. J., Sriram, S. and Rodriguez, M. 1997. Successful treatment of established relapsing experimental autoimmune encephalomyelitis with a monoclonal natural autoantibody. J. Neuroimmunol. 75: 204-209.
Bright, J. J., Topham, D. J., Lodge, P. A. and Sriram, S. 1996. Vaccination with peptides from MHC class II beta chain hypervariable region causes allele specific suppression of EAE. J. Neuroimmunol. 67: 119-124.
John J. Bright, Ph.D
Assistant Professor of Neurology and Pharmacology
Department of Neurology
Vanderbilt University Medical Center
1222F VSRH, 2201 Children's Way
Nashville, TN 37212 , USA .
Tel 615-963-4423, Fax 615-321-5247