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Muralidhar Hegde, PhD

Associate Professor of Radiation Oncology, Institute for Academic Medicine
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. He is an 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 50 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 1500 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

Aurora kinase B dependent phosphorylation of 53BP1 is required for resolving merotelic kinetochore-microtubule attachment errors during mitosis
Wang, H, Peng, BH, Pandita, RK, Engler, DA, Matsunami, RK, Xu, X, Hegde, PM, Butler, BE, Pandita, TK, Mitra, S, Xu, B & Hegde, ML 2017, Oncotarget. DOI:

DNA damage responses in central nervous system and age-associated neurodegeneration
Hegde, ML, Bohr, VA & Mitra, S 2017, Mechanisms of Ageing and Development, vol 161, pp. 1-3. DOI:

Microhomology-mediated end joining is activated in irradiated human cells due to phosphorylation-dependent formation of the XRCC1 repair complex
Dutta, A, Eckelmann, B, Adhikari, S, Ahmed, KM, Sengupta, S, Pandey, A, Hegde, PM, Tsai, M-S, Tainer, JA, Weinfeld, M, Hegde, ML & Mitra, S 2016, Nucleic acids research, vol 45, no. 5, pp. 2585-2599. DOI:

Human AP-endonuclease (APE1) is acetylated at DNA damage sites in chromatin and acetylation modulates its DNA repair activity
Roychoudhury, S, Nath, S, Song, H, Hegde, ML, Bellot, LJ, Mantha, AK, Sengupta, S, Ray, S, Natarajan, A & Bhakat, KK 2016, Molecular and Cellular Biology. DOI:

Oxidized guanine base lesions function in 8-oxoguanine DNA glycosylase-1-mediated epigenetic regulation of nuclear factor ?B-driven gene expression
Pan, L, Zhu, B, Hao, W, Zeng, X, Vlahopoulos, SA, Hazra, TK, Hegde, ML, Radak, Z, Bacsi, A, Brasier, AR, Ba, X & Boldogh, I 2016, The Journal of biological chemistry, vol 291, no. 49, pp. 25553-25566. DOI:

Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A
Yang, C , Sengupta, S, Hegde, PM, Mitra, J, Jiang, S, Holey, B, Sarker, AH, Tsai, M-S, Hegde, ML & Mitra, S 2016, Nucleic acids research, vol 45, no. 2, pp. 739-748. DOI:

TDP-43/FUS in motor neuron disease: Complexity and challenges
Guerrero, EN, Wang, H, Mitra, J, Hegde, PM, Stowell, SE, Liachko, NF, Kraemer, BC, Garruto, RM, Rao, KS & Hegde, ML 2016, Progress in Neurobiology, vol 145-146, pp. 78-97. DOI:

Scaffold attachment factor A (SAF-A) and Ku temporally regulate repair of radiation-induced clustered genome lesions
Hegde, ML, Dutta, A, Yang, C, Mantha, AK, Hegde, PM, Pandey, A, Sengupta, S, Yu, Y, Calsou, P, Chen, D, Lees-Miller, SP & Mitra, S 2016, Oncotarget. DOI:

Chronic oxidative damage together with genome repair deficiency in the neurons is a double whammy for neurodegeneration: Is damage response signaling a potential therapeutic target?
Wang, H, Dharmalingam, P, Vasquez, V, Mitra, J, Boldogh, I, Rao, KS, Kent, TA, Mitra, S & Hegde, ML 2016, Mechanisms of Ageing and Development. DOI:

8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging
German, P, Saenz, D, Szaniszlo, P, Aguilera-Aguirre, L, Pan, L, Hegde, ML, Bacsi, A, Hajas, G, Radak, Z, Ba, X, Mitra, S, Papaconstantinou, J & Boldogh, I 2016, Mechanisms of Ageing and Development. DOI:

Ion-catalyzed reactive oxygen species in sporadic models of parkinson’s disease
Vasquez, V, Mitra, J, Guerrero, EN, Hegde, PM, Rao, KS & Hegde, ML 2016, . in Mitochondrial Mechanisms of Degeneration and Repair in Parkinsons Disease. Springer International Publishing, pp. 75-113. DOI:

Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling
Aguilera-Aguirre, L, Hosoki, K, Bacsi, A, Radák, Z, Sur, S, Hegde, ML, Tian, B, Saavedra-Molina, A, Brasier, AR, Ba, X & Boldogh, I 2015, Free Radical Biology and Medicine, vol 89, pp. 20-33. DOI:

The C-terminal Domain (CTD) of Human DNA Glycosylase NEIL1 Is Required for Forming BERosome Repair Complex with DNA Replication Proteins at the Replicating Genome: Dominant negative function of the CTD
Hegde, PM, Dutta, A, Sengupta, S, Mitra, J, Adhikari, S, Tomkinson, AE, Li, GM, Boldogh, I, Hazra, TK, Mitra, S & Hegde, ML 2015, Journal of Biological Chemistry, vol 290, no. 34, pp. 20919-20933. DOI:

Norepinephrine Reduces Reactive Oxygen Species (ROS) and DNA Damage in Ovarian Surface Epithelial Cells
Patel, PR, Hegde, ML, Theruvathu, J, Mitra, SA, Boldogh, I & Sowers, L 2015, Journal of Bioanalysis & Biomedicine, vol 7, no. 3, pp. 75-80. DOI:

New paradigms in the repair of oxidative damage in human genome: Mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins
Dutta, A, Yang, C, Sengupta, S, Mitra, S & Hegde, ML 2015, Cellular and Molecular Life Sciences, vol 72, no. 9, pp. 1679-1698. DOI:

Revisiting Metal Toxicity in Neurodegenerative Diseases and Stroke: Therapeutic Potential
Mitra, J, Vasquez, V, Hegde, PM, Boldogh, I, Mitra, S, Kent, TA, Rao, KS & Hegde, ML 2015, Neurological Research and Therapy, vol 1, no. 2. DOI:

A Perspective on Chromosomal Double Strand Break Markers in Mammalian Cells
Wang, H, Adhikari, S, Butler, EB, Pandita, TK, Mitra, S & Hegde, ML 2015, Jacobs Journal of Radiation Oncology, vol 1, no. 1:003..

The Role of the Mammalian DNA End-processing Enzyme Polynucleotide Kinase 3’-Phosphatase in Spinocerebellar Ataxia Type 3 Pathogenesis
Chatterjee, A, Saha, S, Chakraborty, A, Silva-Fernandes, A, Mandal, SM, Neves-Carvalho, A, Liu, Y, Pandita, RK, Hegde, ML, Hegde, PM, Boldogh, I, Ashizawa, T, Koeppen, AH, Pandita, TK, Maciel, P, Sarkar, PS & Hazra, TK 2015, PLoS Genetics, vol 11, no. 1, e1004749. DOI:

The role of 8-oxoguanine DNA glycosylase-1 in inflammation
Ba, X, Aguilera-Aguirre, L, Rashid, QTAN, Bacsi, A, Radak, Z, Sur, S, Hosoki, K, Hegde, ML & Boldogh, I 2014, International Journal of Molecular Sciences, vol 15, no. 9, pp. 16975-16997. DOI:

MOF phosphorylation by ATM regulates 53BP1-mediated double-strand break repair pathway choice
Gupta, A, Hunt, CR, Hegde, ML, Chakraborty, S, Udayakumar, D, Horikoshi, N, Singh, M, Ramnarain, DB, Hittelman, WN, Namjoshi, S, Asaithamby, A, Hazra, TK, Ludwig, T, Pandita, RK, Tyler, JK & Pandita, TK 2014, Cell Reports, vol 8, no. 1, pp. 177-189. DOI: