Mitochondrial complex I activity plays a key role in the pathogenesis of Parkinson’s disease (PD), and indirect evidence suggests a role for mitochondrial DNA (mtDNA) mutations. We hypothesize that numerous oxidative stress-induced acquired mutations, each individually present at a low mutational burden, could reach a sufficient aggregate burden to cause mitochondrial dysfunction. The laboratory is focused on genetic analyses and in vitro studies to address the role of oxidative damage to mtDNA and somatic mtDNA mutations in PD. Dr. Simon also is conducting genetic association studies of common genetic variants that may influence the risk of developing PD.
Simon DK, Pulst SM, Sutton JP, Browne S, Beal MF, Johns DR (1999). Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation. Neurology, 53:1787-1794.
Simon DK, Mayeux R, Marder K, Kowall NW, Beal MF, Johns DR (2000). Mitochondrial DNA mutations in complex I and tRNA genes in Parkinson's disease. Neurology, 54:703-709.
Simon DK, Lin MT, Pascual-Leone A. (2002) Nature vs Nurture and Incompletely Penetrant Mutations: Lessons from Twin Studies of Parkinson's Disease. J Neurol Neurosurg Psych, 72:686-689.
Simon DK, Lin MT, Zheng L, Liu G-J, Ahn CH, Kim LM, Beal MF, Johns, D. (2004) Somatic mtDNA mutations in cortex and substantia nigra in aging and Parkinson’s disease. Neurobiol Aging, 25:71-81.
Cantuti-Castelvetri I, Lin MT, Zheng L, Keller-McGandy CE, Betensky RA, Johns DR, Beal MF, Standaert DG, Simon DK. (2005) Somatic mitochondrial DNA mutations in single neurons and glia. Neurobiol Aging 26:1343-55.
External Recognition:
1985 Phi Beta Kappa and Alpha Epsilon Delta Honors Societies
1992 Spencer T. and Ann W. Olin Medical Scientist Fellowship Award
1993 Irwin Levy Prize in Neurology and Neurological Surgery
2001 George C. Cotzias Fellowship Award from American Parkinson's Disease Assoc.
2001 Scientific Advisory Board Member, BostonCure Project for Multiple Sclerosis
2005 Grant Review Committee: Michael J Fox Foundation RFA on Biomarkers for Parkinson’s Dis.
2005 – 2007 Pfizer/AFAR Innovations in Aging Research Award
2005–current Assistant Medical Director; BIDMC Parkinson’s Disease and Movement Disorders Center, a National Parkinson Foundation Center of Excellence.
2006 The William F. Milton Fund of Harvard University; Research Award.
2006 NIH Study Section Ad Hoc Reviewer: Neurological Sciences and Disorders A (Nov, 2006)
2006 – 2007 National Parkinson Foundation “Mega-Research Project” Award (Co-Investigator)
2007 Parkinson’s Disease Society UK Study Section ad hoc grant reviewer
2008 National Scientific Advisory Committee, AFAR (American Federation for Aging Research)
2007-9 Michael J. Fox Foundation “Target Validation” Award
2007-current: American Neurological Association (ANA) Active Member
2008 Grant Review Committee: Michael J Fox Foundation RFA on Cognition and Mood in Park. Dis.
2008 NIH Study Section Ad Hoc Reviewer: Molecular Neurogenetics (MNG)
Major Collaborative Activities:
1. Collaboration with Dr. Ippolita Cantuti-Castelvetri (MGH) to investigate somatic mitochondrial DNA mutations in aging and in Parkinson's disease using Laser Capture Microdissection.
2. Collaboration with Dr. Bruce Spiegelman (Dana Farber Cancer Institute) to investigate the role of a transcriptional coactivator, PGC-1 alpha, in Parkinson's disease.
