The Haque Lab

Photo of Azizul Haque

Azizul Haque, Ph.D.
Associate Professor
Microbiology and Immunology

Education
1997-2003 Postdoctoral Fellow, Indiana University School of Medicine
1997 Ph.D., Saga Medical School, Japan

Contact Info
haque@musc.edu
Tel: 843-792-9466
BSB 208

Research Interests
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

Cancer Immunology and Immunotherapy:

Hathaway-Schrader JD, Norton D, Hastings K, Doonan BP, Fritz ST, Bethard JR, Blum JS, Haque A. GILT expression in human melanoma cells enhances generation of antigenic peptides for HLA class II-mediated immune recognition. Int J Mol Sci. 2022 Jan 19;23(3):1066.

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.

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.

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.

Immune Regulation in Autoimmunity, Inflammation, and Neurodegeneration:

Haque A, Das A, Samantaray S, Matzelle D, Capone M, Wallace G, Husarik AN, Taheri S, Reiter RJ, Varma A, Ray SK, Banik NL. Premarin Reduces Neurodegeneration and Promotes Improvement of Function in an Animal Model of Spinal Cord Injury. Int J Mol Sci. 2022 Feb 21;23(4):2384.

Gao A, McCoy HM, Zaman V, Shields DC, Banik NL, Haque A. Calpain activation and progression of inflammatory cycles in Parkinson's disease. Front Biosci (Landmark Ed). 2022 Jan 13;27(1):20.

Haque A, Drasites KP, Cox A, Capone M, Myatich AI, Shams R, Matzelle D, Garner DP, Bredikhin M, Shields DC, Vertegel A, Banik NL. Protective Effects of Estrogen via Nanoparticle Delivery to Attenuate Myelin Loss and Neuronal Death after Spinal Cord Injury. Neurochem Res. 2021 Nov;46(11):2979-2990.

Zhao D, Hajiaghamohseni LM, Liu X, Szulc ZM, Bai A, Bielawska A, Norris JS, Reddy SV, Hannun YA, Haque A. Inhibition of acid ceramidase regulates MHC class II antigen presentation and suppression of autoimmune arthritis. Cytokine. 2020 Nov;135:155219.

Polcyn R, Capone M, Matzelle D, Hossain A, Chandran R, Banik NL, Haque A.  Enolase inhibition alters metabolic hormones and inflammatory factors to promote neuroprotection in spinal cord injury. Neurochem Int. 2020 Oct;139:104788.

Haque A, Samantaray S, Knaryan VH, Capone M, Hossain A, Matzelle D, Chandran R, Shields DC, Farrand AQ, Boger HA, Banik NL. Calpain mediated expansion of CD4+ cytotoxic T cells in rodent models of Parkinson's disease. Exp Neurol. 2020 Aug;330:113315.

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.

Polcyn R, Capone M, Matzelle D, Lueking B, Walker A, Kau E, Haque A, Banik N. Cytokine/chemokine dysregulation in progressive MS patient is apparent and can be modulated by calpain inhibition.  Metab Brain Dis. 2020 Feb;35(2):255-261. doi: 10.1007/s11011-019-00521-1. Epub 2019 Dec 18.

 

Research Support
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
Role: PI

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
Role: Co-I

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.
Role: PI

1R21NS118393-01 Haque&Banik (MPI) 07/01/20-06/30/22 NIH/NINDS
Calpain cleavage of α-synuclein and T-cell reactivity in Parkinson’s disease
The major goal of the project is to determine whether alterations in calpain activity affect α-synuclein processing and T-cell reactivity in Parkinson’s disease
Role: PI

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