Houston Methodist. Leading Medicine.
Houston Methodist. Leading Medicine

Muralidhar Hegde Ph.D.

Muralidhar L. Hegde, Ph.D.


Assistant Member 
Houston Methodist Research Institute

Department of Radiation Oncology
Houston Methodist Neurological Institute
Houston Methodist Hospital

E-mail: mlhegde@houstonmethodist.org
Phone: 713-441-7456


Education

B.S.   Karnatak University, Karnataka, India (Chemistry, Biology)
M.S.   Karnatak University, Karnataka, India (Biochemistry)
Ph.D.   

University of Mysore, Karnataka, India (Biochemistry/Neurochemistry) 

Postdoctoral Training

Postostdoctoral Associate, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX

 

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 a faculty (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 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 and the Chinese Journal of Biology.

Dr. Hegde has published 38 peer-reviewed publications including ones as corresponding author. He has also published five book chapters and fundamental review articles which have received nearly 1000 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.

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), Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). 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 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.

Major Areas of Research

Genome damage response, DNA repair, neurodegenerative diseases, Alzheimer’s disease, Parkinson’s disease

Recent Publications

Hegde ML, Hegde PM, Bellot LJ, Mandal SM, Hazra TK, Li GM, Boldogh I, Tomkinson AE, Mitra S. Prereplicative repair of oxidized bases in the human genome is mediated by NEIL1 DNA glycosylase together with replication proteins. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):E3090-9.  PMID: 23898192

Hegde ML, Tsutakawa SE, Hegde PM, Holthauzen LM, Li J, Oezguen N, Hilser VJ, Tainer JA, Mitra S. The disordered C-terminal domain of human DNA glycosylase NEIL1 contributes to its stability via intramolecular interactions. J Mol Biol. 2013 Jul 10;425(13):2359-71.  PMID: 23542007

Hegde ML, Hegde PM, Arijit D, Boldogh I, Mitra S. Human DNA Glycosylase NEIL1's Interactions with Downstream Repair Proteins Is Critical for Efficient Repair of Oxidized DNA Base Damage and Enhanced Cell Survival. Biomolecules. 2012 Nov 15;2(4):564-578. PMID: 23926464 

Hegde ML, Banerjee S, Hegde PM, Bellot LJ, Hazra TK, Boldogh I, Mitra S. Enhancement of NEIL1 protein-initiated oxidized DNA base excision repair by heterogeneous nuclear ribonucleoprotein U (hnRNP-U) via direct interaction. J Biol Chem. 2012 Oct 5;287(41):34202-11. PMID: 22902625

Mandal SM, Hegde ML, Chatterjee A, Hegde PM, Szczesny B, Banerjee D, Boldogh I, Gao R, Falkenberg M, Gustafsson CM, Sarkar PS, Hazra TK. Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome. J Biol Chem. 2012 Jan 20;287(4):2819-29.  PMID: 22130663

Hegde ML, Hegde PM, Rao KS, Mitra S. Oxidative genome damage and its repair in neurodegenerative diseases: function of transition metals as a double-edged sword. J Alzheimers Dis. 2011;24 Suppl 2:183-98. PMID: 21441656

Hegde ML, Hegde PM, Holthauzen LM, Hazra TK, Rao KS, Mitra S. Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases. J Biol Chem. 2010 Sep 10;285(37):28812-25.  PMID: 20622253

Hegde ML, Vasudevaraju P, Rao KJ. DNA induced folding/fibrillation of alpha-synuclein: new insights in Parkinson's disease. Front Biosci (Landmark Ed). 2010 Jan 1;15:418-36. PMID: 20036828

Hegde ML, Bharathi P, Suram A, Venugopal C, Jagannathan R, Poddar P, Srinivas P, Sambamurti K, Rao KJ, Scancar J, Messori L, Zecca L, Zatta P. Challenges associated with metal chelation therapy in Alzheimer's disease. J Alzheimers Dis. 2009;17(3):457-68.  PMID: 19363258

Hegde ML, Theriot CA, Das A, Hegde PM, Guo Z, Gary RK, Hazra TK, Shen B, Mitra S. Physical and functional interaction between human oxidized base-specific DNA glycosylase NEIL1 and flap endonuclease 1. J Biol Chem. 2008 Oct 3;283(40):27028-37. PMID: 18662981