Pooja Jain

Pooja Jain, Ph.D.

Assistant Professor, Microbiology and Immunology

Ph.D., 2001, Central Drug Research Institute, Lucknow, UP, India

245 N. 15th Street
Mail Stop 1013A, Room 18311
Philadelphia, PA 19102
Tel: 215-762-8586
Fax: 215-762-1955
Email: pjain@drexemed.edu

Keywords:

Dendritic cells, neuroinflammation, Human T cell leukemia virus type 1 (HTLV-1), toll-like receptors and c-type lectin pathways, HIV-1/HCV-1 co-infection, tight junction proteins

Research Interests:

Dendritic cells (DCs) are the most potent antigen presenting cells and have long been recognized as key regulators of the immune system, linking both stimulatory and inhibitory components of normal immunity. While DCs are well characterized with respect to primary and secondary immune responses, their unique role in coordinating central and peripheral tolerance is not fully delineated.
It is increasingly evident that the failure of DCs’ ability to maintain tolerance can lead to autoimmune and/or inflammatory diseases. For the past few years our efforts have been focused on exploring the participation of DCs in virus-induced neuroinflammation using human T cell leukemia virus type 1 (HTLV-1) as a model pathogen. HTLV-1 is the etiologic agent of two immunologically distinct diseases; adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic debilitating neuroinflammatory disease with similarities to multiple sclerosis. The humoral and cellular immune responses during HAM/TSP are directed to the HTLV-1 transactivator protein Tax that is oncogenic in nature. The molecular mimicry exhibited by anti-Tax antibodies to neuronal antigen (hnRNAP A1) and intense proliferation of chronically activated Tax-specific cytotoxic CD8+ T lymphocytes (CTLs) support the autoimmune nature of the disease. Therefore, HAM/TSP demonstrates a clear link between chronic viral infection and autoimmune disease of the CNS and allows for the direct comparison of the infecting agent with host antigens providing important insights into the pathogenesis of MS and other neuroinflammatory diseases.
Currently three different projects are underway to investigate how DC functions are modulated during the progression of HTLV-1-associated neuroinflammation:

Project 1
deals with defining the role of various DC subsets (myeloid and plasmacytoid) in regulating Tax-specific CTL response and associated neuroinflammation under three different experimental settings: in vitro using primary DC culture systems, ex vivo in HAM/TSP patients, and in vivo in a mouse model of neuroinflammation. Ultimate goal of this project is to determine how DC biology can be harnessed to enhance or silence its function in disease-specific manner.

Project 2 deals with identifying dendritic cell surface molecules that serve as potential receptor for viral binding, entry, and transmission.
One such candidate receptor is DC-SIGN (a C-type lectin) that is currently being exploited in our high throughput screening program as antiviral drug target to identify novel viral binding inhibitors against both HTLV-1 envelope glycoprotein gp46 and HIV-1 gp120.

Project 3 is focused on the processing and presentation (direct and cross) of Tax protein through Class I MHC pathway. We have recently shown that Tax serves as a potential TLR (toll-like receptor) ligand and represents a way to understand TLR involvement in Class I presentation pathway, an area that remained unexplored so far despite the established role of TLRs in Class II antigen presentation pathway. TLRs are the integral component of innate immunity and are becoming increasingly important in vaccine development.

In addition, we recently began to investigate changes in the expression of tight junction proteins on dendritic cells (blood DCs and those in gut biopsies) during HIV-1/HCV-1 co-infection using cohorts of patients that are infected with HIV-1 alone, HCV-1 alone or both. The main goal of this project is to understand how does modulation in DC phenotype and functions during HIV-1 infection increase susceptibility to HCV-1 infection. Finally, migration of DCs across blood-brain barrier also represents an area of our current interest.

Selected Publications:

Jain P., I. Akula and T. D. Edlind. The cyclic AMP signaling pathway modulates susceptibility of Candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors. Antimicrobial Agents and Chemotherapy, 47: 3195-3201, 2003.
Mostoller, K., C. Norbury, P. Jain, and B. Wigdahl. Human T cell leukemia virus type I Tax induces the expression of dendritic cell markers associated with maturation and activation. Journal of Neurovirology, 10: 358-371, 2004.
Alefantis, T., P. Jain, J. Ahuja, K. Mostoller, and B. Wigdahl. HTLV-1 Tax nucleocytoplasmic shuttling, interaction with the secretory pathway, extracellular signaling, and implications for neurologic disease. Journal of Biomedical Science, 12: 961-974, 2005.
Alefantis, T., K. Mostoller, P. Jain, E. Harhaj, C. Grant, and B. Wigdahl. Secretion of the human T cell leukemia virus type I transactivator protein Tax. Journal of Biological Chemistry, 280: 17353-17362, 2005.
Grant, C., P. Jain, M. Nonnemacher, B. Irish, K. E. Flaig, J. Ahuja, A. Alexaki, T. Alefantis, and B. Wigdahl. AP-1-directed human T cell leukemia virus type 1 viral gene expression during monocytic differentiation. Journal of Leukocyte Biology, 80: 640-650, 2006.
Ahuja, J., K. Kampani, B. Wigdahl, S. Datta, K. E. Flaig, and P. Jain. Use of human antigen presenting cell gene array profiling to examine the effect of human T cell leukemia virus type 1 Tax on primary human dendritic cells. Journal of Neurovirology, 12: 47-59, 2006.
Jing, Y., C. Grant, E. Harhaj, M. Nonnemacher, T. Alefantis, J. Martin, P. Jain, and B. Wigdahl. Regulation of human T cell leukemia virus type 1 gene expression by Sp1 and Sp3 interaction with TRE-1 repeat III. DNA and Cell Biology, 25: 262-276, 2006.
Grant, C., M. Nonnemacher, P. Jain, D. Pandya, B. Irish, S. C. Williams, and B. Wigdahl. CCAAT/Enhancer-binding proteins modulate human T cell leukemia virus type 1 long terminal repeat activation. Virology 348: 354-369, 2006.
Jain, P., J. Ahuja, Z. K. Khan, S. Shimizu, O. Meucci, S. Jennings, and B. Wigdahl. Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1. Journal of Leukocyte Biology, 82: 44-56, 2007.
Alefantis, T., K. E. Flaig, B. Wigdahl, and P. Jain. Interaction of HTLV-1 Tax protein with calreticulin: Implication for Tax nuclear export and secretion. Biomedicine and Pharmacotherapy, 61: 194-200, 2007.
Kampani, K., K. Quann, J. Ahuja, B. Wigdahl, Z. K. Khan, and P. Jain. A novel high throughput quantum dot-based fluorescence assay for quantitation of virus binding and attachment. Journal of Virological Methods, 141: 125-132, 2007.
Ahuja, J., V. Lepoutre, B. Wigdahl, Z. K. Khan, and P. Jain. Induction of proinflammatory cytokines by human T cell leukemia virus type 1 Tax protein as determined by multiplexed cytokine protein array analyses of human dendritic cells. Biomedicine and Pharmacotherapy, 61: 201-208, 2007.
Manuel, S., S. Rahman, B. Wigdahl, Z. K. Khan, and P. Jain. Dendritic cells in autoimmune diseases and neuroinflammatory disorders. Frontiers in Bioscience, 12: 4315-4335, 2007.
Pandya, D., S. Rahman, B. Wigdahl, Z. K. Khan, and P. Jain. New insights into the pathogenesis, diagnosis, and treatment of human T cell leukemia virus type 1-induced disease. Future Virology, 2:481-493, 2007.
Jain, P., Mostoller, K., Flaig, K. E., Pandya, D., Alefantis, T., and B. Wigdahl. Identification of HTLV-1 Tax amino acid signals and cellular factors involved in secretion of the viral oncoprotein. Journal of Biological Chemistry, 282: 34581-34593, 2007.

Patent:

Lakshmi V., K. Pandey, A. Saxena, K. P. Madhusudanan, M. N. Srivastava, Z. K. Khan, P. Jain, G. Gupta, and J. D. Dhar (2004). Isolation of bivittoside D from sea cucumber and activity thereof. US patent no. U015092-8.