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Dr. Anil K. Mantha

Associate Professor
Centre for Animal Sciences
Central University of Orissa
India

Biography

Dr. Anil K. Mantha Associate Professor Centre for Animal Sciences 

Research Interest

 My research interest underscores examining various DNA repair and regulatory proteins to understand the molecular mechanisms and pathways through which the processes associated with onset of aging, age related, and neurodegenerative disorders in developing potential therapeutic targets. I am urrently working on regulatory and repair functions of AP-endonuclease (APE1) in mammalian genomes. APE1 is the main apurinic/apyrimidinic endonuclease in eukaryotic cells playing a central role in the Base Excision repair (BER) pathway of all DNA lesions (uracil, alkylated and oxidized and abasic sites) including single-strand breaks and has role in co-transcriptional activation of TFs such as AP-1, NF-κB, TP53 and HIF1 α, and named redox effecter factor-1 (Ref-1). APE1/Ref-1 is a vital protein with its biological activities located in two functionally distinct domains. The N-terminus, containing the nuclear localization signal (NLS) region, is principally devoted to the redox activity and protein-protein interactions, while the C-terminus exerts the enzymatic activity on the AP sites of DNA. My own interest lies in elucidating the neuro-protective role of APE1/Ref-1 in neurological disorders e.g., Alzheimer’s disease (AD) and Parkinson’s disease (PD). Due to its multi-functional nature; it is proving to be a critical target in neuronal cancer therapy for “Glioblastoma”. APE1/Ref-1’s role as a neuroprotector is an unexplored field of neurodegenerative disorders. Furthermore, the expression of APE1/Ref-1 and its sub-cellular localization is still poorly investigated in case of AD and PD. My research work is mainly focused to understand and elucidate the molecular mechanisms of genotoxicity associated with amyloid beta (Aβ) protein deposits in human brain tissue and role of APE1/Ref-1 as a potential candidate for therapeutic intervention in AD using neuronal cell lines as model system. 1. Oxidative Stress and Cancer Biology. 2. DNA Damage-Repair (Single-Strand Base Repair via Base Excision Repair (BER)-pathway) and Human Diseases. 3. DNA Repair and Regulatory Functions of Apurinic/Apyrimidinic (AP) Endonuclease (APE1/Ref-1). 4. Amyloid Beta (Aβ) Neurotoxicity and Alzheimer’s Disease (AD).

Publications

  • Tsutakawa SE, Shin DS, Mol CD, Izumi T, Arvai AS, Mantha AK, Szczesny B, Ivanov IN, Hosfield DJ, Frankel KA, Hitomi K, Cunningham RP, Mitra S, Tainer JA. Common geometric basis for apurinic/apyrimidinic endonuclease catalytic activity in structurally nonhomologous APE1 and Endonuclease IV. J. Biological Chemistry. 2013. 288(12):8445-55.

  • Kaur N, Dhiman M, Perez-Polo, JR, and Mantha AK. Ginkgolide B Revamps Neuroprotective Role of APE1 and Mitochondrial OXPHOS Against Aβ(25-35)-Induced Neurotoxicity in Human Neuroblastoma Cells. Journal of Neuroscience Research. 2015. 93: 938-947.

  • Bhakat, K., Sengupta, S., Adeniyi, V., Roychoudhury, S., Nath, S., Bellot, L., Feng, D., Mantha, A., Sinha, M., Qiu, S., & Luxon, B. (2016). Regulation of limited Nterminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation. Oncotarget, 5. 2016.

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