Associate Professor and AHFMR/AI-HS Senior Scholar, Division of Surgical-Medical Research Institute, Department of Surgery
Immunoregulation, vaccines, T cells and dendritic cells
The general research interests of my lab are in the area of T-cell responses and their regulation in context of hepatitis C virus infection, cancer and autoimmune diseases.
Current Research Activities
We are studying the components of T-cell immune responses important in clearing hepatitis C virus (HCV) infection, and the correlates associated with chronic disease progression, viral clearance and/or protection against disease progression. The ultimate goal of these studies is to identify the role of cellular immune responses in protecting or combating chronic HCV infection, in order to design and study novel vaccine and immunotherapeutic strategies.
In the second project we strive to understand the exact role of MUC1 on T-cell activation and their connection with tumors and/or tumor immunotherapy. In earlier studies, we have demonstrated that MUC1 mucin, largely considered to be an epithelial antigen and a marker for epithelial tumor cells, is also expressed by activated human T-cells. We are examining the role of MUC1 in regulating T-cell responses and their mechanisms.
In addition, we are working on novel, immunomodulatory agents for use in autoimmune diseases and transplantation.
MSc (Biochemistry), PhD (Immunology)
Konowalchuk J., and Agrawal B. MUC1 is a novel costimulatory molecule of human T cells and functions in a NF-AT-dependent manner. Human Immunology, 2012, 73, 448-455.
Shakya N., Vedi S., Liang C., Agrawal B., Tyrrell DL, and Kumar R. A New Class of Pyrimidine Nucleosides: Inhibitors of Hepatitis B and C Viruses. Bioorg Med Chem Lett. In Press. 2012.
Konowalchuk J., and Agrawal B. MUC1 mucin is expressed on human T regulatory cells: Function in both co-stimulation and co-inhibition. Cellular Immunology, 2012, 272:193-199.
Shakya N, Srivastav NC, Bhavanam S, Tse C, Agrawal B., Kunimoto DY, Kumar R. Discovery of novel 5-(ethyl or hydroxymethyl) analogs of 2’-‘up’ fluoro (or hydroxyl) pyrimidine nucleosides as a new class of Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium inhibitors. Bioorg Med Chem., 2012, 20(13), 4088-97.
Kumar, R., and Agrawal, B. Broader Use of hepatitis B virus vaccine: Efficacy in those who lost Hepatitis B Surface Antigen During Follow-up. Hepat Mon. 2011;11(6):477-478.
Vivithanaporn P. Mangat F. Ma H, Richardson, CD, Agrawal B, Cohen E, Jhamandas J, Power C. HCV core protein induces neuroimmune activation and potentiates HIV mediated neurotoxicity. PLos One. 2010, 5(9):e12856.
Yao Q, Fischer KP, Li L, Agrawal B, Berhane Y, Tyrrell, DL, Gutfreund K, Pasick, J. Immunogenicity and protective efficacy of a DNA vaccine encoding a chimeric protein of avian influenza hemagglutinin subtype H5 fused to CD154 (CD40L) in Pekin ducks. Vaccine. 2010 Nov 29; 28(51):8147-56
Krishnadas DK, Ahn JS, Han J, Kumar R, Agrawal B. Immunomodulation by hepatitis C virus-derived proteins: targeting human dendritic cells by multiple mechanisms. Int Immunol. 2010, 22(6), 491-502.
Krishnadas DK, Li W, Kumar R, Tyrrell DL, Agrawal B. HCV-core and NS3 antigens play disparate role in inducing regulatory or effector T cells in vivo: Implications for viral persistence or clearance. Vaccine. 2010, 28(9), 2104-14.
Srivastav NC, Shakya N, Mak M, Liang C, Tyrrell DL, Agrawal B, Kumar R. Synthesis and in vitro antiviral activities of 3'-fluoro (or chloro) and 2',3'-difluoro 2',3'-dideoxynucleoside analogs against hepatitis B and C viruses. Bioorg Med Chem. 2010, 18, 7542-7547.
Srivastav NC, Mak M, Agrawal B, Tyrrell DL, Kumar R. Antiviral activity of 2,3'-anhydro and related pyrimidine nucleosides against hepatitis B virus. Bioorg Med Chem Lett. 2010, 20, 6790-6793.
Srivastav NC, Shakya N, Mak M, Agrawal B, Tyrrell DL, Kumar R. Antiviral Activity of Various 1-(2'-Deoxy-β-d-lyxofuranosyl), 1-(2'-Fluoro-β-d-xylofuranosyl), 1-(3'-Fluoro-β-d-arabinofuranosyl), and 2'-Fluoro-2',3'-didehydro-2',3'-dideoxyribose Pyrimidine Nucleoside Analogues against Duck Hepatitis B Virus (DHBV) and Human Hepatitis B Virus (HBV) Replication. J Med Chem. 2010, 53, 7156-7166.
Srivastav NC, Rai D, Tse C, Agrawal B, Kunimoto DY, Kumar R. Inhibition of mycobacterial replication by pyrimidines possessing various C-5 functionalities and related 2'-deoxynucleoside analogues using in vitro and in vivo models. J Med Chem. 2010, 53(16), 6180-7.
Shakya N, Srivastav NC, Desroches N, Agrawal B, Kunimoto DY, Kumar R. 3'-bromo analogues of pyrimidine nucleosides as a new class of potent inhibitors of Mycobacterium tuberculosis. J Med Chem. 2010, 53(10), 4130-40.
Krishnadas DK, Li W, Kumar R, Tyrrell LJ, Agrawal B. In vitro activation and differentiation of naïve CD4+ and CD8+ T cells into HCV core- and NS3-specific armed effector cells: a new role for CD4+ T cells. Cell Immunol. 2009, 259(2), 141-9.
Li W, Krishnadas DK, Kumar R, Tyrrell DL, Agrawal B. Priming and stimulation of hepatitis C virus-specific CD4+ and CD8+ T cells against HCV antigens NS4, NS5a or NS5b from HCV-naive individuals: implications for prophylactic vaccine. Int Immunol. 2008, 20(1), 89-104.
D. Rai, M. Johar, N.C. Srivastav, T. Manning, C. Tse, B. Agrawal, D. Kunimoto, and R. Kumar. Inhibition of M. tuberculosis, M. bovis and M. avium by novel dideoxy nucleosides. J Med Chem 50, 4766-4774, 2007.
M. Johar, T. Manning, C. Tse, N. Desroches, B. Agrawal, D. Kunimoto, and R. Kumar. Growth inhibition of M. bovis, M. tuberculosis and M. avium in vitro: Effect of 1--D-2’-arabinofuranosyl and 1-(2’-deoxy-2’-fluoro--D-2’-ribofuranosyl) pyrimidine nucleoside analogs. J Med Chem, 50, 3690-3705, 2007.
J. S. Ahn, D.K. Krishnadas and B. Agrawal. Dendritic Cells Partially Abrogate the Regulatory Activity of CD4+CD25+ T Cells Present in the Human Peripheral Blood. International Immunology, 19, 227-237, 2007.
B Agrawal. Dendritic cells and hepatitis C virus. Current Immunol. Rev., 2006.
W Li, DK Krishnadas, J Li, DLJ Tyrrell, B Agrawal. Induction of primary human T cell responses against hepatitis C virus derived antigens NS3 or core by autologous dendritic cells expressing HCV antigens: Potential for vaccine and immunotherapy. Journal of Immunology, 176, 6065-6075, 2006.
W Li, J Li, DLJ Tyrrell, B Agrawal. Expression of hepatitis C virus (HCV) derived core of NS3 antigens in human dendritic cells leads to induction of pro-inflammatory cytokines and normal T cell stimulation capabilities. Journal of General Virology, 87, 61-72, 2006.
*Pictures of research findings highlighted as cover page on the January 2006 issue.
W Semaine, M Johar, DLJ Tyrrell, R Kumar, B Agrawal. Effect of Various Pyrimidines Poessessing 1-[(2-Hydroxy-1-(hydroxymethyl) ethoxy)methyl] Moiety Able to Mimic Natural 2’-Deoxyribose, on Wild-type and Mutant Hepatitis B Virus Replication. J Med Chem 49, 3693-3700, 2006.
R Kumar, W Semaine, M Johar, DLJ Tyrrell, B Agrawal. Inhibition of Hepatitis B Virus (HBV) Replication by Pyrimidines Bearing Acyclic Moiety: Effect on Wild-type and Mutant HBV, J Med Chem, 49, 2049-2054, 2006.
JS Ahn, B Agrawal. IL-4 is more effective than IL-13 for in vitro differentiation of dendritic cells from peripheral blood mononuclear cells. International Immunology, 17:1337-1346, 2005.
B Agrawal, BM Longenecker. Functional role of MUC1 in human T cell activation. International Immunology, 17, 391-399, 2005.
B Agrawal, J Li, MJ Krantz, BM Longenecker, J Parker. Regulation of human T cell response through MUC1 expression. Immunology, 429-434, 2004.
R Kumar, B Agrawal. Novel treatment options for hepatitis viruses’ infection. Current Opinion in Investigational Drugs, 5, 171-178, 2004.
P Mukherjee, CS Madsen, AR Ginardi, TL Tinder, F Jacobs, J Parker, B Agrawal, M. Longenecker, S.J. Gendler. Anti-MUC1 immunotherapy elicits strong cellular immune response in mice with spontaneous tumors of breast and pancreas. Journal of Immunotherapy, 26, 47-62, 2003.
P Mukherjee, AR Ginardi, CS Madsen, TL Tinder, F Jacobs, J Parker, B Agrawal, M Longenecker, SJ Gendler. MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment. Glycoconjugate Journal, 18, 931-942, 2003.
R Mukherjee, P Chaturvedi, B Agrawal, B Singh. Regulation of type-1 diabetes by a self-MHC class II peptide: role of transforming growth factor beta (TGF-beta). Cell Mol Biol, 49, 159-169, 2003.
P Chaturvedi, B Agrawal, MA Zechel, E. Lee-Chan, B Singh. A self MHC class II ß chain peptide prevents diabetes in NOD mice. Journal of Immunology, 164, 6610-6620, 2000.
B Agrawal, MJ Krantz, M Reddish, BM Longenecker. Adenocarcinoma associated MUC-1 mucin molecules inhibit human T cell responses. Nature Medicine, 4, 43-49, 1998.
*Received press coverage as Research News in “BioCentury”, 6(5), B13, Jan 1998.
B Agrawal, MA Reddish, A van Heel, B Christian, L Tang, RR Koganty, BM Longenecker. Use of BCP8 monoclonal antibody to isolate MHC class I associated MUC1 derived peptides from the surface of adenocarcinoma cells. Cancer Research, 58, 5151-5156, 1998.
B Agrawal, MJ Krantz, J Parker, BM Longenecker. Expression of MUC1 mucin on activated human T cells: Implications for a role of MUC1 in normal immune regulation. Cancer Research, 58, 4079-4081, 1998.
*Received press coverage as basic science Research News in “Applied Genetics News”, Vol. 20, No. 5, pp.1-2, Dec 1999.
B Agrawal, MJ Krantz, M Reddish, BM Longenecker. Rapid generation of human CD4+ and CD8+ T cells against cancer associated MUC1 mucin. International Immunology, 10, 1907-1916, 1998.
B Agrawal, SJ Gendler, BM Longenecker. The biological role of mucins in cellular interactions and immune regulation: Prospects for cancer immunotherapy. Molecular Medicine Today, 4, 397-403, 1998.
B Agrawal, MA Reddish, BM Longenecker. CD30 expression on human CD8+ T cells isolated from peripheral blood lymphocytes of normal donors. Journal of Immunology, 157, 3229-3234, 1996.
B Agrawal, M Reddish, BM Longenecker. In vitro induction of MUC-1 peptide specific type-1 T lymphocyte and cytotoxic T lymphocyte responses from healthy multiparous donors. Journal of Immunology, 157, 2089-2095, 1996.
B Agrawal, M Reddish, MJ Krantz, BM Longenecker. Does pregnancy prime against breast cancer? Cancer Research, 55, 2257-2261, 1995.
B Agrawal, E Fraga, K Kane, B Singh. Up-regulation of the MHC class II molecules on B cells by peptide ligands. Journal of Immunology, 152, 965-975, 1994.
B Singh, B Rider, B Agrawal, Q Yu, E Fraga. A novel role for immunogenic peptides in the assembly and expression of class II MHC molecules on B lymphocytes. Peptides Chemistry, Structure & Biology, 709-711, 1993.
B Agrawal, M Manickasundari, E Fraga, B Singh. T cells which recognize peptides of self MHC class II molecules exist in syngeneic mice. Journal of Immunology, 147, 383-390, 1991.
B Agrawal, BM Longenecker. Telomerase specific cancer vaccine. Australian patent #781376, May 2005.
B Agrawal, BM Longencker. Methods of detecting T cell activation. U.S. patent #6,602,660, August 2003.
B Agrawal, M Krantz, MR Reddish and BM Longenecker. Modified MUC1 derivatives. U.S. patent #6,600,012, July 2003.
B Agrawal, BM Longenecker. Methods of detecting T cell activation. Australian patent #755017, March 2003.
BM Longenecker. Methods of detecting T cell activation and treating disorders associated with T-cell dysfunction. U.S. patent
#6,114,129, September 2000.