Education

• 1992-1993. University of Aarhus, Denmark Visiting Scientist
  
• 1994-1996, Auburn University, AL Sr. Research Fellow
  
• 1997-2003, Institute for Cellular Therapeutics, University of Louisville, KY
  
• Ph. D., 1991. Academy of Sciences, St. Petersburg (Russia) UNESCO

Research

TCDD (Dioxin) induced Immunotoxicity and Molecular Mechanisms
My lab is interested in understanding the molecular pathways through which environmental toxicants alter the immune functions. TCDD (dioxin) is one of the most toxic compounds generated as a byproduct from chlorinated phenols or during combustion of chlorinated materials, and becomes available as an environmental pollutant and a carcinogen. It triggers apoptosis (programmed cell death) of T cells and causes thymic atrophy and peripheral immunosuppression. My lab is investigating how activation of Ah receptor by TCDD on immune cells transcriptionally regulates various apoptotic genes including Fas and Fas ligand (FasL).

Therapeutic efficacy of Resveratrol for treatment of autoimmune diseases (Multiple sclerosis, Lupus, and diabetes)
We are also interested in investigating whether resveratrol, a phytoalexin found in grapes and red wines can be used as an anti-inflammatory agent for the treatment of various autoimmune diseases (multiple sclerosis, lupus, diabetes etc). Resveratrol acts as a ligand for aryl hydrocarbon receptor (AhR) and promotes translocation of AhR from cytosol to the nucleus and induces various transcription factors leading to upregulation of various genes. We have observed resveratrol-induced upregulation of Fas and FasL in T cells and apoptosis. We have also observed that resveratrol interacts with estrogen receptors (ER). We are currently studying anti-inflammatory properties of resveratrol, molecular mechanisms involved, and use of resveratrol as a therapeutic agent to cure various autoimmune diseases (multiple sclerosis, lupus, diabetes etc).

Publications

• Kotakadi1, VS, Jin, Y, Hofseth, AB., Ying, L, Cui, X, Wood, PA, Price, RL., McFadden, A, Singh, UP, N. P. Singh, Nagarkatti, M, Nagarkatti, PS., Matesic, LE., Auclair, K, Wargovich, MJ., and Hofseth, LJ.. 2008. Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis. Carcinogenesis. 29(9):1799-1806.
• Hegde, V. L., N. P. Singh, Prakash Nagarkatti, and Mitzi Nagarkatti. 2008. CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation. J Leukoc Biol. 84(1):134-142.
• Singh, N.P., Mitzi Nagarkatti, and Prakash S. Nagarkatti. 2008. Primary peripheral T cells become susceptible to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)-mediated apoptosis in vitro upon activation and in the presence of dendritic cells. Mol Pharmacol. 73: 1722-1735.
• Singh NP, Hegde, V., Hofseth, L.J., Nagarkatti, M. and Nagarkatti, P. 2007. Resveratrol (trans-3,5,4'-trihydroxystilbene) Ameliorates Experimental Allergic Encephalomyelitis (EAE) Primarily via Induction of Apoptosis in T cells Involving Activation of AhR and ER. Mol Pharmacol. 72:1508-1521.
• Eplek, K.G., Chantale Lacelle, N. P. Singh, Esma S. Yolcu, and Haval Shirwan. 2007. CD4+CD25+ T Regulatory Cells Dominate Multiple Immune Evasion Mechanisms in Early but Not Late Phases of Tumor Development in a B Cell Lymphoma Model. Journal of Immunology. 178(11):6840-6848.
• Singh, N.P., Mitzi Nagarkatti, and Prakash S. Nagarkatti. 2007. Role of dioxin response element (DRE) and NF-kappaB (NF-kB) motifs in TCDD (2,3,7,8-Tetrachlorodibenzo-p-Dioxin)-mediated regulation of Fas and Fas Ligand expression. Molecular Pharmacology. 71.145-157.
• Wentao Jia, Venkatesh L. Hegde, N. P. Singh, Daniel Sisco, Steven Grant, Mitzi Nagarkatti, and Prakash S. Nagarkatti. 2006. Delta 9-tetrahydrocannabinol-induced apoptosis in leukemic cells is regulated by translocation of Bad to mitochondria through disruption of RAF/MEK/ERK/RSK pathway. Molecular Cancer Research. 4(8):549-562.
• Singh, N.P., R.W. Miller, E. Yolcu, M.O. Kilinc, M. Oechsli, R. Huseby, D.D. Taylor, M.T. Perry, R.V. LaRocca, and Haval Shirwan. 2006. Primary tumor cells from cancer patients decorated with a novel form of CD80 protein serve as effective antigen-presenting cells for the induction of autologous T-cell immune responses ex vivo. Human Gene Therapy. 17:334-346.
• Kilinc, M.O., L. Mukundan, E.S. Yolcu, N.P. Singh, J. Suttles, and H. Shirwan. 2006. Generation of multimeric form of CD40L with potent immunomodulatory activity using streptavidin as a chepron. Experimental and Molecular Pathology. 80:252-261.
• Singh, N.P., E.S. Yolcu, N. Askenasy, Haval Shirwan. 2005. ProtEx^TM: A novel technology to display exogenous proteins on the cell surface and its use in immunomodulation for the treatment of cancer. Annals of New York Academy of Sciences. 1056:344-358.
• Camacho, I. A., N.P. Singh, Venkatesh L. Hegde, Mitzi Nagarkatti, and Prakash S. Nagarkatti. 2005. Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin leads to AhR-dependent nuclear translocation of NF-κB and expression of FasL in thymic stromal cells and consequent apoptosis in T cells. Journal of Immunology. 175(1): 90-103. Received “Best Paper of the Year Award” by Society of Toxicology. 2007.
• Singh, N. P., Luping Guo, Xingyi Que, and Haval Shirwan. 2004. Blockade of the indirect recognition pathway mediated by CD4+ T cells leads to prolonged cardiac xenograft survival. Xenotransplantation. 10, 33-42.
• Singh, N. P., Esma S. Yolcu, Douglas D. Taylor, Cicek Gercel-Taylor, Daniel S. Metzinger, Stephen K. Dreisbach and Haval Shirwan. 2003. A novel approach to cancer immunotherapy: tumor cells decorated with CD80 generate effective antitumor immunity. Cancer Research. 63,4067-4073.
• Singh, N. P., Luping Guo, Anna Mhoyan, and Haval Shirwan. 2003. Predominant expression of Th2 cytokines and IFN-g in acutely rejected xenografts. Transplantation. 75, 586-590.
• Yolcu, E. S., N. Askenasy*. N.P. Singh.* Equal contribution, Lamhamedi Cherradi, H. Shirwan. 2002. Modification of the cell membrane for rapid display of exogenous proteins as a novel means of immunomodulation: FasL-decorated splenocytes prevent islet allograft rejection. Immunity, 17: 795-808.
• Singh, N. P. and Haval Shirwan. 2000. Immunobiology of xenotransplantation. In S. G. Pandalai (ed.), Recent Research Developments in Immunology (Part-I). 2, 347-373.
• Lawrence, C. B., N.P. Singh, J. Qiu, R. G. Gardner, and Sadik Tuzun. 2000. Constitutive hydrolytic enzymes are associated with polygenic resistance of tomato to Alternaria solani and may function as an elicitor release mechanism. Physiological and Molecular Plant Pathology. 57, 211-220.
• Singh, N. P. and Haval Shirwan. 2000. Indirect recognition and Th2 response play critical roles in cardiac xenograft rejection. Transplantation. 69, No 8: 257.
• Singh, N. P., X. Que, and H. Shirwan. 1999. Contribution of the Indirect Recognition Pathway to Cardiac Graft Rejection in the Rat-to-Mouse Xenograft Model. Transplantation. S 555.
• Singh, N. P. and A. O. Zalensky. 1997. Changes in structural organization of bacterial Sym-plasmid during Pisum sativum-rhizobium leguminosarum bv viciae symbiosis. The Nucleus. 40 (1,2): 13-21.
• Singh, N. P., J. A. Brennan, D. Niemeyer, K. J. Shuler, G. H. Veltri, J. C. Egan, and V. G. DelVecchio. 1997. Novel detection methods for rare malignant cells and histologically benign surgical margins and lymph nodes. Otolaryngology-Head and Neck Surgery. 117 (2): P30.
• Shaw, J. J., J. Wu, N.P. Singh, W. Mahaffee, F. Dane, and A. E. Brown. 1996. Bioluminescent, Antibiotic and Chromogenic markers for bacteria. In Linda S. Thomashow (ed.), The Manual of Environment Microbiology, 1st ed. ASM Press, Washington D. C., USA, PP 466-472.
• Singh, N. P., M. Moore, D. Niemeyer, J. Brennan, and V. G. DelVecchio. 1996. Detection of mutations in p53 gene by a rapid non-isotopic PCR-based method. Clinical Chemistry. 42: 1894.
• Peteroziello, J. M., N.P. Singh, T. Scialla, J. Brennan, and V. G. DelVecchio. 1996. Detection of p53 gene mutations via analysis of fluorophore enhanced PCR-generated DNA and cleavage assay length polymorphism assay. Clinical Chemistry. 42: 1894.
• Singh, N. P., A. O. Zalensky, and Erik O. Jensen. 1996. Nucleosomal structure of Soybean (Glycine max.L.) root nodules and seedling chromatin. The Nucleus. 38: 85-90.
• Bers, E. P., N. P. Singh, V. A. Pardenen, L. A. Lutova, and A. O. Zalensky. 1992. Nucleosomal structure and Histone H1 Subfractional composition of Pea (Pisum sativum) root nodules, radicles and callus chromatin. Plant Molecular Biology. 20: 1089-1096.
• Singh, N. P., A. O. Zalensky, and V. I. Vorobev. 1991. Easy and fast method of isolating intact nuclei from Pea seedlings and nodules and analysis of nuclear proteins. The Nucleus. 34 (3): 155-157.
• Singh, N. P. and A. O. Zalensky. 1991. Plant nodulins and their role in Symbiotic Nitrogen Fixation. Symposium on Plant-Pathogen Interactions of Indian Society of Plant Pathology, Ranchi, India. PP: 16-17.
• Singh, N. P., A. O. Zalensky and V. I. Vorobev. 1991. Changes in sub-fractional composition of linker histone (H1) during development of nodules in Pisum sativum. Proceedings of the Golden Jubilee Symposium of Indian Society of Genetics and Plant Breeding, New Delhi, India. PP872-873.
• Singh, N. P. and A. O. Zalensky. 1990. Comparative characteristics of chromatin of nodule and seedling of Pea. Nucleosomal organization of Promoter region of Leg-hemoglobin gene. Research journal of Agricultural Microbiology. 53: 33-35.
• Singh, N. P., E. P. Bers and A. O. Zalensky. 1990. Nuclear Proteins and Chromatin structure of Pea (Pisum sativum L.) root nodule. The Nucleus. 33 (3): 124-128.