天美传媒

Stanley H. Appel, M.D. is the Peggy and Gary Edwards Distinguished Endowed Chair for the Treatment and Research of ALS, Department of Neurology, Neurological Institute, Houston Methodist Hospital, and Professor of Neurology at Weill Medical College of Cornell University. He was previously Chair of the Department of Neurology at Baylor College of Medicine as well as Chief of the Neurology division and the James B. Duke Professor of Medicine at Duke University Medical Center, North Carolina. Dr. Appel is a native of Massachusetts and received his Bachelor Degree at Harvard University and his Medical Degree from Columbia College of Physicians and Surgeons. He is Director of the MDA/ALS Research and Clinical Center at the Methodist Neurological Institute, and past Director of a National Institute of Aging Alzheimer鈥檚 Disease Research Center.

Dr. Appel is a member of numerous professional societies and committees and is the author of 15 published books and over 350 articles on topics such as ALS, neuromuscular disease, Alzheimer鈥檚 Disease, and Parkinson鈥檚 Disease. He has received a number of awards for his accomplishments in Neurology and Biochemistry, including the Gold Medal Award in 1997 from Columbia College of Physicians and Surgeons for 鈥淒istinguished Achievements in Medicine鈥�, the Sheila Essey Award in 2003 from the American Academy of Neurology for 鈥渙utstanding research in Amyotrophic Lateral Sclerosis鈥�, Elected Fellow of the American Association for the Advancement of Science in recognition of the 鈥渄edication and commitment to advancing science and serving society鈥� in 2003, Baylor College of Medicine Alumni Association Distinguished Faculty Award in 2004, MDA鈥檚 Wings Over Wall Street Diamond Award in 2004, Texas Neurological Society Lifetime Achievement Award in 2005 and the Forbes Norris Award for 鈥渃ompassion and love for humanity in research and treatment in patients with ALS鈥� from the International Alliance of ALS/MND Associations in 2005, and the Museum District Business Alliance Award in recognition of his commitment to research, patient care, and education, 2007, and the recipient of the Houston Academy of Medicine 2008 John P. McGovern Compleat Physician Award. He is also named 2008 Best of the Best Physicians by the Medical Journal of Houston.

Research in Dr. Appel鈥檚 laboratory has focused on developing new insights into neurodegenerative diseases with primary emphasis on ALS. His studies of mutant SOD transgenic mice have documented that neuroinflammation and activated microglia are neuroprotective during the early stages of the disease and cytotoxic during the late stages of the disease. The early stages start within motor neurons and appear cell-autonomous, whereas later stages involve innate immune glia and are non-cell-autonomous. These two stages appear to be modulated by peripheral T-cells that enter the CNS at sites of neuronal injury; Th2 and regulatory T-cells are increased in early stages and appear to provide neuroprotection, while Th1 T-cells are increased in later stages and mediate cytotoxicity. Transplantation of ALS mice with regulatory T cells prolonged disease duration by more than 80%. Our comparable studies in human ALS have employed PCR techniques to confirm the presence of activated microglia and to demonstrate the presence of CD4 T-cells as well as immature and mature dendritic cells and enhanced chemokine signaling. Our laboratory was the first to document that regulatory T lymphocytes modulate disease progression in ALS patients. More specifically, regulatory T lymphocytes are decreased in ALS patients that progress at a faster rate; the levels of Treg may thus serve as a biomarker of rates of disease progression. His current efforts are focused on enhancing the protective immunity of Treg cells and anti-inflammatory microglia, and decreasing the pro-inflammatory immunity of Th1 effector lymphocytes and proinflammatory microglia.

Education

Ph.D., Nagasaki University
M.S., Tohoku College of Pharmacy
B.S., Tohoku College of Pharmacy
 

Academic Positions

Research Scientist, Duke University School of Medicine
Research Associate Senior, Duke University School of Medicine
Postdoctoral Associate, Duke University School of Medicine
Associate Professor, Nagasaki University Graduate School of Biomedical Sciences

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Professional Affiliations

American Association of Immunologists

Patents
Shinohara ML, Inoue M; Duke University “Methods of optimizing disease treatment” U.S. # 13/347,233 (Utility Application Filed 1/10/2012)

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 translational research contributions.



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
BS, Karnataka University