Department of Microbiology and Immunology
Azizul Haque, PhD
1997-2003 Postdoctoral Fellow, Indiana University School of Medicine
1997 Ph.D., Saga Medical School, Japan
Dr. Haque's laboratory conducts research in the areas of tumor immunology, transplantation immunology and autoimmunity. In tumor immunology, we are investigating the mechanisms by which malignant tumors such as lymphoma, prostate and melanoma evade immune recognition via MHC class I and II pathways. Lymphoid malignancies such as B-cell lymphomas arise at distinct stages of cellular development and maturation, potentially influencing immune recognition and the functional interaction of these cells with other components of the immune system. Burkitt lymphoma (BL) is a highly malignant B-cell tumor characterized by chromosomal translocation that constitutively activates the c-myc oncogene. Epstein-Barr virus (EBV) transforms primary B-cells in vitro, and results in the establishment of lymphoblastoid cell lines (B-LCL). While B-LCL efficiently process and present antigens to T cells in the context of both MHC class I and class II molecules, BL cells have been shown to be deficient in their ability to process and present antigens by both pathways, and the mechanisms remain unknown. Studies in Dr. Haque's laboratory are probing the factors responsible for defective antigen processing and immune recognition in the context of MHC class II molecules. While MHC class I-restricted CD8+ T cells are effector cells in anti-tumor immune responses, MHC class II-restricted CD4+ T cells can also destroy tumors by direct killing. CD4+ T cells can also play critical roles in initiating, regulating, and maintaining anti-tumor immune responses. Because most B-cell tumors express MHC class II molecules, these tumors can be potential target for CD4+ T cells. Elucidating the mechanisms of loss of immune recognition in the context of MHC class II molecules will contribute to the development of effective immunotherapeutics against B-cell lymphomas.
In transplantation immunology, we are investigating the regulation of immune responses in lung allograft rejection using a rat model of lung transplantation. In collaboration with Dr. Wilkes (Indiana University), we have found that the immune responses during lung allograft rejection may be directed against certain connective tissue proteins such as type V collagen. Ongoing studies in the laboratory are actively investigating the implications of collagen V-reactive T cells in the immunopathogenesis of chronic lung allograft rejection. Dr. Haque's laboratory is also investigating the role of small molecules in the suppression of autoimmune diseases.
Recent Publications | Additional Publications
God JM, Haque A. (2010) Burkitt lymphoma: pathogenesis and immune evasion. J Oncololy doi: 10.1155/2010/516047. Epub 2010 Oct 5
Norton DL, Haque A. (2009) Insights into the role of GILT in HLA class II antigen processing and presentation by melanoma. J Oncololy 2009:142959.
Younger AR, Amria S, Jeffrey WA, Mahdy A, Goldstein OG, Norris JS, Haque A. (2008) HLA class II antigen presentation by prostate cancer cells. Prostate Cancer Prostatic Dis 11:334-41.
Amria S, Hajiaghamohseni LM, Harbeson C, Zhao D, Goldstein O, Blum JS, Haque A. (2008) HLA-DM negatively regulates HLA-DR4-restricted collagen pathogenic peptide presentation and T-cell recognition. Eur J Immunol 38:1961-1970.
Amria S, Cameron CA, Stuart RK, Haque A. (2008) Defects in HLA class II antigen presentation in B-cell lymphomas. Leuk Lymphoma 49:353-5.
Goldstein OG, Hajiaghamohseni LM, Amria S, Sundaram K, Sakamuri V. Reddy SV, Haque A. (2008) Gamma-IFN-inducible-lysosomal thiol reductase modulates acidic proteases and HLA class II antigen processing in melanoma. Cancer Immunol and Immunother 57:1461-1470.
Haque A, Das A, Hajiaghamohseni LM, Younger A, Banik NL, Ray SK. (2007) Induction of apoptosis and immune response by all-trans retinoic acid plus interferon-gamma in human glioblastoma T98G and U87MG cells. Cancer Immunol Immunother 56:615-25.
Yoshida S, Haque A, Mizobuchi T, Iwata T, Chiyo M, Webb T, Baldridge LA, Heidler KM, Cummings OW, Fujisawa T, Blum JS, Brand DD, Wilkes DS. (2006) Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants. Am J Transplant 6:724-35.
Srinivasan M, Debao L, Rajaraman E, Brand D, Haque A, Blum JS. (2005) CD80 binding polyproline helical peptide inhibits T cell activation. J Biol Chem 280:10149-55.
Haque A, Li P, Jackson SK, Zarour HM, Hawes JW, Phan UT, Maric M, Cresswell P, Blum JS. (2002) Absence of gamma-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes. J Exp Med 195:1267-1277.
Title: Disruption of HLA Class II-mediated Immune recognition of B-celllLymphomas
Funding Period: 03/01/2009 - 11/30/2013
Title: Disruption of HLA Class II-mediated immune recognition of B-cell lymphomas
Agency: NCI/NIH, Supplement
Funding Period: 06/01/2009 - 07/31/2011
Title: Calpain activation of T cells in demyelinating disease
Funding Period: 04/01/2006 - 04/31/2011
Title: Attenuation of axonal damage and neuronal death in EAE
Funding Period: 07/01/2006 - 06/30/2011
Title: Inflammation and degeneration of optic nerve in EAE
Funding Period: 07/01/2006 - 06/30/2012