Azizul Haque, Ph.D.
Microbiology and Immunology
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 cancer immunology, inflammation, and neurodegeneration. In cancer 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 inflammation and neurodegeneration studies, we are investigating the role of inflammatory cytokines/growth factors in the regulation of immune responses in multiple sclerosis (MS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). In collaboration with Dr. Banik (Neurosurgery MUSC), we have found that the immune responses and the inflammatory factors may be directed against calpain (calcium activated neutral protease) which is a target in many autoimmune and neurodegenerative diseases. Ongoing studies in the laboratory are actively investigating the implications of calpain isoforms in the immunopathogenesis of MS, PD and AD. Dr. Haque's laboratory is also actively investigating the role of enolase and calpain isoforms in spinal cord injury (SCI), autoimmunity and neurodegeneration. We have recently shown that elevation of enolase is deleterious as it promotes extracellular degradation and production of inflammatory cytokines/chemokines and metabolic factors which activates glia and damages neurons. Thus, our current focus is to investigate the implications of NSE in neuroinflammation, neurodegeneration, and neuroprotection in SCI and various neurodegenerative diseases for prognostic and therapeutic potential.
Recent Publications | Additional Publications
Anjum A, Biswas S, Rahman M, Rahman A, Siddique AE, Karim Y, Aktar S, Nikkon F, Haque A, Himeno S, Hossain K, Saud ZA. Butyrylcholinesterase-a potential plasma biomarker in manganese-induced neurobehavioral changes. Environ Sci Pollut Res Int. 2019 Mar;26(7):6378-6387. doi: 10.1007/s11356-018-04066-1. Epub 2019 Jan 7. PMID: 30617895
Johnson BM, Radwan FFY, Hossain A, Doonan BP, Hathaway-Schrader JD, God JM, Voelkel-Johnson CV, Banik NL, Reddy SV, Haque A. Endoplasmic reticulum stress, autophagic and apoptotic cell death, and immune activation by a natural triterpenoid in human prostate cancer cells. J Cell Biochem. 2019 Apr;120(4):6264-6276. doi: 10.1002/jcb.27913. Epub 2018 Oct 30. PMID: 30378157
Tanu T, Anjum A, Jahan M, Nikkon F, Hoque M, Roy AK, Haque A, Himeno S, Hossain K, Saud ZA. Antimony-Induced Neurobehavioral and Biochemical Perturbations in Mice. Biol Trace Elem Res. 2018 Mar 8. doi: 10.1007/s12011-018-1290-5. [Epub ahead of print]. PMID: 29520725
Haque A, Polcyn R, Matzelle D, Banik NL. New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection. Brain Sci. 2018 Feb 18;8(2). pii: E33. doi: 10.3390/brainsci8020033. Review. PMID: 29463007
Trager NNM, Butler JT, Harmon J, Mount J, Podbielska M, Haque A, Banik NL, Beeson CC. A Novel Aza-MBP Altered Peptide Ligand for the Treatment of Experimental Autoimmune Encephalomyelitis. Mol Neurobiol. 2018 Jan;55(1):267-275. doi: 10.1007/s12035-017-0739-4. PMID: 28889362
Hathaway-Schrader JD, Doonan BP, Hossain A, Radwan FFY, Zhang L, Haque A Autophagy-dependent crosstalk between GILT and PAX-3 influences radiation sensitivity of human melanoma cells. J Cell Biochem. 2018 Feb;119(2):2212-2221. doi: 10.1002/jcb.26383. Epub 2017 Oct 18. PMID: 28857256
Haque A, Capone M, Matzelle D, Cox A, Banik NL. Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in Rats. Neurochem Res. 2017 Oct;42(10):2777-2787. doi: 10.1007/s11064-017-2291-z. Epub 2017 May 15. PMID: 28508172
Individual and Combined Effects of Arsenic and Lead on Behavioral and Biochemical Changes in Mice. Aktar S, Jahan M, Alam S, Mohanto NC, Arefin A, Rahman A, Haque A, Himeno S, Hossain K, Saud ZA. Biol Trace Elem Res. 2017 Jun;177(2):288-296. doi: 10.1007/s12011-016-0883-0. Epub 2016 Oct 27. PMID: 27787814
Elevation of c-MYC disrupts HLA class II-mediated immune recognition of human B cell tumors. God JM, Cameron C, Figueroa J, Amria S, Hossain A, Kempkes B, Bornkamm GW, Stuart RK, Blum JS, Haque A. J Immunol. 2015 Feb 15;194(4):1434-45. doi: 10.4049/jimmunol.1402382. Epub 2015 Jan 16. PMID: 25595783
VA (1I01BX004269-01A1) Haque/Banik (MPI) 11/01/18 – 09/30/22
Attenuation of Inflammatory Response in Progressive Neurodegeneration in Parkinson's Disease
The goal of this project is to investigate the role of calpain in the pathogenesis of Parkinson's Disease (PD) in a mouse model of PD
VA (2I01BX001262-05A2) Banik (PI) 10/01/18 – 09/30/22
Hormonal Intervention Protects Axon-myelin to Promote Functional Recovery in SCI
The goal of this proposal is to determine the role of a novel estrogen-loaded nanoparticle gel patch in protecting neuronal loss in SCI
SCIRF #2018 I-01 Haque (PI) 01/01/19 – 12/31/20
Nanoparticle Delivery of ENOblock and Recovery of Function in SCI
The goal of this project is to determine the efficacy of a novel small molecule inhibitor of enolase in a preclinical model of spinal cord injury.
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