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Muralidhar Hegde, PhD

Professor of Neurosurgery, Academic Institute
Full Member, Research Institute
Houston Methodist
Weill Cornell Medical College


Hegde Lab


mlhegde@houstonmethodist.org
Biography

Dr. Hegde earned his Ph.D. in Biochemistry and Neurosciences from the University of Mysore, India in 2006. He performed his graduate research at the Max-Planck Institute of Biophysical Chemistry, Gottingen, Germany as a DST-DAAD visiting fellow, and at the Indian Institute of Science (IISc), Bangalore, India. He held an Assistant Professor appointment at the University of Texas Medical Branch at Galveston, Texas, USA before becoming a member of the Houston Methodist Research Institute in 2013. As a member of the Research Institute cancer and neuroscience research programs, he directs a research program focusing on understanding the role of genome damage repair in cell death (neurodegenerative diseases) and cell proliferation (cancer) and its potential exploitation in therapeutics. Dr. Hegde has also been a member of grant review boards for the Alzheimer’s Association, USA, Netherlands Organization for Scientific Research, French Scientific Grants (FMRM) and the Motor Neuron Disease Association, UK, in addition to NIH and DOD-CDMRP study sections. He is a Deputy Chief Editor for the Springer Journal Metabolic Brain Disease and Associate Editor for the Journal of Alzheimer’s Disease and serves on the editorial boards of the American Journal of Neurodegenerative Diseases, Jacobs Journal of Radiation Oncology and Research, Journal Neuroscience Research and Therapeutics, the Chinese Journal of Biology, and a peer-reviewer for more than 30 international journals.

Dr. Hegde has published over 90 peer-reviewed publications including more than a dozen as senior author. He has also published five book chapters, edited a book on ALS and four journal special issue collections.  These articles have received nearly 3000 citations. He has received several awards including gold medals in Masters, New Investigator awards from the Alzheimer’s Association, the Environmental Mutagenesis Society, Researcher of the Month (May 2011) at UTMB and prestigious Gopal Krishna Memorial Young Scientist award from ASIOA. He has recently been awarded the Career Cornerstone award from Houston Methodist for outstanding contribution to translational research.

Description of Research

Dr. Hegde’s research program focuses on delineating the molecular mechanisms underlying neurodegenerative diseases with a primary emphasis on genome damage and their repair inhibitions/deficiencies in neurons. His laboratory is interested in Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease (PD) and Stroke. He showed that DNA repair inhibitions/deficiencies play a key role in the etiology of neurodegenerative diseases. He demonstrated that transition metals, iron and copper, act as a ‘double whammy’ by both inducing DNA damage and by inhibiting their repair via direct binding and oxidation of NEIL enzymes involved in oxidized DNA base repair. These studies were funded by American Parkinson’s Disease Association. His current studies focus on characterizing the role of ALS-linked RNA binding protein TDP-43 in DNA double-strand break repair and testing the hypothesis that TDP-43’s nuclear clearance and aggregation in ALS (and other neurodegenerative diseases) cause deficient DNA double-strand repair and contributes significantly to cell death. In another project funded by Alzheimer’s Association’s New Investigator grant, he is delineating the mechanism of genotoxicity of amyloid proteins and exploring its prevention by natural compounds. In collaboration with Dr. Sankar Mitra, he is also exploring the potential of genome repair inhibitions in cancer therapeutics. Dr. Hegde’s research program is supported by NIH/NINDS R01, Muscular Dystrophy Association, ALS Association, Alzheimer’s Association and Melo Foundation.

Areas Of Expertise

Genome damage response DNA repair Neurodegenerative diseases Alzheimer’s disease Parkinson’s disease Amyotrophic Lateral Sclerosis (ALS Stroke
Education & Training

Postdoctoral Associate, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston
MS, Karnataka University
PhD, University of Mysore, Karnataka
Publications

Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin
Bacolla, A, Sengupta, S, Ye, Z, Yang, C, Mitra, J, De-Paula, RB, Hegde, ML, Ahmed, Z, Mort, M, Cooper, DN, Mitra, S & Tainer, JA 2021, , Nucleic Acids Research, vol. 49, no. 1, pp. 221-243. https://doi.org/10.1093/nar/gkaa1120

The Chemical Basis of Intracerebral Hemorrhage and Cell Toxicity With Contributions From Eryptosis and Ferroptosis
Derry, PJ, Vo, ATT, Gnanansekaran, A, Mitra, J, Liopo, AV, Hegde, ML, Tsai, AL, Tour, JM & Kent, TA 2020, , Frontiers in Cellular Neuroscience, vol. 14, 603043. https://doi.org/10.3389/fncel.2020.603043

Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin
Bacolla, A, Sengupta, S, Ye, Z, Yang, C, Mitra, J, De-Paula, RB, Hegde, ML, Ahmed, Z, Mort, M, Cooper, DN, Mitra, S & Tainer, JA 2020, , Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa1120

Emerging Roles of Non-canonical RNA Binding Proteins in the Repair of Genome Damage Linked to Human Pathologies
Mitra, J, Wang, H, Kodavati, M, Mitra, S & Hegde, ML 2020, . in DNA Damage, DNA Repair and Disease: Volume 1. vol. 1, The Royal Society of Chemistry, United Kingdom, pp. 301-322. https://doi.org/10.1039/9781839160769-00301

Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin.
Hegde, M, Mitra, S, Sengupta, S, Bacolla, A, Ye, Z, Yang, C, Mitra, J, Tainer, JA & Ahmed, Z 2020, , Nucleic Acids Research.

Ligand-induced gene activation is associated with oxidative genome damage whose repair is required for transcription
Sengupta, S, Wang, H, Yang, C, Szczesny, B, Hegde, ML & Mitra, S 2020, , Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 36, pp. 22183-22192. https://doi.org/10.1073/pnas.1919445117

XRCC1 promotes replication restart, nascent fork degradation and mutagenic DNA repair in BRCA2-deficient cells
Eckelmann, BJ, Bacolla, A, Wang, H, Ye, Z, Guerrero, EN, Jiang, W, El-Zein, R, Hegde, ML, Tomkinson, AE, Tainer, JA & Mitra, S 2020, , NAR cancer, vol. 2, no. 3, pp. zcaa013. https://doi.org/10.1093/narcan/zcaa013

Amyotrophic Lateral Sclerosis: Recent Advances and Therapeutic Challenges
Hegde, M (ed.) 2020, . InTech. https://doi.org/10.5772/intechopen.78121

Molecular basis of DNA repair defects in FUS-associated ALS: implications of a new paradigm and its potential as therapeutic target
Wang, H & Hegde, M 2020, . in IntechOpen Open Access book, "Amyotrophic Lateral Sclerosis - Recent Advances and Therapeutic Challenges" edited by Dr. Muralidhar L. Hegde, 2020 . InTech. https://doi.org/10.5772/intechopen.92637

The Role of TDP-43 in Genome Repair and beyond in Amyotrophic Lateral Sclerosis
Hegde, M & Mitra, J 2020, . in ML Hegde (ed.), Amyotrophic Lateral Sclerosis - Recent Advances and Therapeutic Challenges. InTech. https://doi.org/DOI: 10.5772/intechopen.92696

Altered Mitochondrial Dynamics in Motor Neuron Disease: An Emerging Perspective
Kodavati, M, Wang, H & Hegde, M 2020, , Cells, vol. 9, no. 4. https://doi.org/10.3390/cells9041065

Deficiency in classical nonhomologous end-joining-mediated repair of transcribed genes is linked to SCA3 pathogenesis
Chakraborty, A, Tapryal, N, Venkova, T, Mitra, J, Vasquez, V, Sarker, AH, Duarte-Silva, S, Huai, W, Ashizawa, T, Ghosh, G, MacIel, P, Sarkar, PS, Hegde, ML, Chen, X & Hazra, TK 2020, , Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 14, pp. 8154-8165. https://doi.org/10.1073/pnas.1917280117

Pervasive Genomic Damage in Experimental Intracerebral Hemorrhage: Therapeutic Potential of a Mechanistic-Based Carbon Nanoparticle
Dharmalingam, P, Talakatta, G, Mitra, J, Wang, H, Derry, PJ, Nilewski, LG, McHugh, EA, Fabian, RH, Mendoza, K, Vasquez, V, Hegde, PM, Kakadiaris, E, Roy, T, Boldogh, I, Hegde, VL, Mitra, S, Tour, JM, Kent, TA & Hegde, M 2020, , ACS Nano, vol. 14, no. 3, pp. 2827-2846. https://doi.org/10.1021/acsnano.9b05821

A multi-faceted genotoxic network of alpha-synuclein in the nucleus and mitochondria of dopaminergic neurons in Parkinson's disease: Emerging concepts and challenges
Vasquez, V, Mitra, J, Wang, H, Hegde, PM, Rao, KS & Hegde, ML 2020, , Progress in Neurobiology, vol. 185, 101729. https://doi.org/10.1016/j.pneurobio.2019.101729

Emerging Roles of Non-Canonical RNA Binding Proteins in Repair of Genome Damage Linked to Human Pathologies
Hegde, M, Mitra, J, Wang, H, Kodavati, M & Mitra, S 2020, . in Royal Society of Chemistry (UK) Book on DNA Damage, Repair and Disease, edited by M. Didzagaralu and Lloyd S. 2020.

Acute and chronic mitochondrial electron transport chain dysfunction treatments and Graphenic materials for use thereof
Hegde, M, Hegde, PM, Mitra, J, Dharmalingam, P, Kent, TA, M. Tour, J & Derry, PJ, , Patent No. 18730149.4-1112.

RT2 PCR array screening reveals distinct perturbations in DNA damage response signaling in FUS-associated motor neuron disease
Wang, H, Rangaswamy, S, Kodavati, M, Mitra, J, Guo, W, Guerrero, EN, Van Den Bosch, L & Hegde, M 2019, , Molecular Brain, vol. 12, no. 1, 103. https://doi.org/10.1186/s13041-019-0526-4

Carotenoids as Novel Therapeutic Molecules Against Neurodegenerative Disorders: Chemistry and Molecular Docking Analysis
Lakey-Beitia, J, Kumar D, J, Hegde, ML & Rao, KS 2019, , International journal of molecular sciences, vol. 20, no. 22, PMID: 31703296 , pp. 20(22). pii: E5553. https://doi.org/10.3390/ijms20225553

Hexahydropyrrolo[2,3- b]indole Compounds as Potential Therapeutics for Alzheimer's Disease
Doens, D, Valdés-Tresanco, ME, Vasquez, V, Carreira, MB, De La Guardia, Y, Stephens, DE, Nguyen, VD, Nguyen, VT, Gu, J, Hegde, ML, Larionov, OV, Valiente, PA, Lleonart, R & Fernández, PL 2019, , ACS Chemical Neuroscience, vol. 10, no. 10, pp. 4250-4263. https://doi.org/10.1021/acschemneuro.9b00297

Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer's disease from a ferroptosis perspective
Derry, PJ, Hegde, ML, Jackson, GR, Kayed, R, Tour, JM, Kent, TA & Tsa, A-L 2020, , Progress in Neurobiology, vol. 184, 101716, pp. 101716. https://doi.org/10.1016/j.pneurobio.2019.101716