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Muralidhar Hegde, PhD

Associate Professor of Neurosurgery, Academic Institute
Associate 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 75 peer-reviewed publications including more than a dozen as senior author. He has also published five book chapters and fundamental review articles which have received nearly 5000 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

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, M, 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, M 2020, Progress in Neurobiology, vol. 185, 101729. https://doi.org/10.1016/j.pneurobio.2019.101729

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

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

Amyotrophic lateral sclerosis-associated TDP-43 mutation Q331K prevents nuclear translocation of XRCC4-DNA ligase 4 complex and is linked to genome damage-mediated neuronal apoptosis
Guerrero, EN, Mitra, J, Wang, H, Rangaswamy, S, Hegde, PM, Basu, P, Rao, KS & Hegde, ML 2019, Human Molecular Genetics, vol. 28, no. 18, pp. 3161-3162. https://doi.org/10.1093/hmg/ddz141

Amyotrophic lateral sclerosis-associated TDP-43 mutation Q331K prevents nuclear translocation of XRCC4-DNA ligase 4 complex and is linked to genome damage-mediated neuronal apoptosis
Guerrero, EN, Mitra, J, Wang, H, Rangaswamy, S, Hegde, PM, Basu, P, Rao, KS & Hegde, M 2019, Human Molecular Genetics, vol. 28, no. 5, pp. 2459-2476. https://doi.org/10.1093/hmg/ddz062

Loss of endosomal recycling factor RAB11 coupled with complex regulation of MAPK/ERK/AKT signaling in postmortem spinal cord specimens of sporadic amyotrophic lateral sclerosis patients
Mitra, J, Hegde, PM & Hegde, M 2019, Molecular Brain, vol. 12, no. 1, 55. https://doi.org/10.1186/s13041-019-0475-y

Cannabinoid exposure during pregnancy and its impact on immune function
Dong, C, Chen, J, Harrington, A, Vinod, KY, Hegde, M & Hegde, VL 2019, Cellular and Molecular Life Sciences, vol. 76, no. 4, pp. 729-743. https://doi.org/10.1007/s00018-018-2955-0

Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects
Mitra, J, Guerrero, EN, Hegde, PM, Liachko, NF, Wang, H, Vasquez, V, Gao, J, Pandey, A, Paul Taylor, J, Kraemer, BC, Wu, P, Boldogh, I, Garruto, RM, Mitra, S, Rao, KS & Hegde, M 2019, Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 10, pp. 4696-4705. https://doi.org/10.1073/pnas.1818415116

New mechanisms of dna repair defects in fused in sarcoma–associated neurodegeneration: Stage set for dna repair-based therapeutics?
Wang, H & Hegde, M 2019, Journal of Experimental Neuroscience, vol. 13. https://doi.org/10.1177/1179069519856358

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, M, Larionov, OV, Valiente, PA, Lleonart, R & Fernández, PL 2019, ACS Chemical Neuroscience. https://doi.org/10.1021/acschemneuro.9b00297

A Commentary on TDP-43 and DNA Damage Response in Amyotrophic Lateral Sclerosis
Mitra, J & Hegde, M 2019, Journal of Experimental Neuroscience, vol. 13. https://doi.org/10.1177/1179069519880166

Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response
Zhang, D, Dong, Y, Zhao, Y, Zhou, C, Qian, Y, Hegde, M, Wang, H & Han, S 2018, Oncology Reports, vol. 40, no. 5, pp. 2886-2895. https://doi.org/10.3892/or.2018.6693

Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis
Wang, H, Guo, W, Mitra, J, Hegde, PM, Vandoorne, T, Eckelmann, BJ, Mitra, S, Tomkinson, AE, Van Den Bosch, L & Hegde, ML 2018, Nature communications, vol. 9, no. 1, 3683. https://doi.org/10.1038/s41467-018-06111-6

Heterocyclic Analogs of Sulforaphane Trigger DNA Damage and Impede DNA Repair in Colon Cancer Cells: Interplay of HATs and HDACs
Okonkwo, A, Mitra, J, Johnson, GS, Li, L, Dashwood, WM, Hegde, M, Yue, C, Dashwood, RH & Rajendran, P 2018, Molecular Nutrition and Food Research, vol. 62, no. 18, 1800228. https://doi.org/10.1002/mnfr.201800228

Acetylation of oxidized base repair-initiating NEIL1 DNA glycosylase required for chromatin-bound repair complex formation in the human genome increases cellular resistance to oxidative stress
Sengupta, S, Yang, C, Hegde, ML, Hegde, PM, Mitra, J, Pandey, A, Dutta, A, Datarwala, AT, Bhakat, KK & Mitra, S 2018, DNA Repair, vol. 66-67, pp. 1-10. https://doi.org/10.1016/j.dnarep.2018.04.001

An inducible alpha-synuclein expressing neuronal cell line model for Parkinson's disease
Vasquez, V, Mitra, J, Perry, G, Rao, KS & Hegde, M 2018, Journal of Alzheimers Disease, vol. 66, no. 2, pp. 453-460. https://doi.org/10.3233/JAD-180610

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