Email

jmshulma@bcm.edu

Positions

Professor

Neurology, Neuroscience, and Molecular & Human Genetics
Baylor College of Medicine

Investigator

Jan and Dan Duncan Neurological Research Institute
Texas Children's Hospital

Addresses

Parkinson's Disease Center and Movement Disorders Clinic (Clinic)

Baylor College of Medicine Medical Center
McNair Campus
Houston, TX 77030
United States
Phone: (713) 798-2273
https://www.bcm.edu/healthcare/care-centers/neurology

Duncan Neurological Research Institute (Lab)

Room: DNRI-N.1150
Houston, TX 77030
United States

Education

Post-Doctoral Fellowship at Brigham And Women's Hospital

01/2012 - Boston, MA United States

Neurogenetics

Clinical Fellowship at Massachusetts General Hospital

01/2010 - Boston, MA United States

Movement & Memory Disorders

Residency at Harvard Medical School Affiliate Hospitals

01/2009 - Boston, MA United States

Neurology

Internship at Massachusetts General Hospital

01/2006 - Boston, MA United States

Medicine

MD from Harvard Medical School

01/2005 - Boston, MA United States

Medicine

PhD from University Of Cambridge

01/2000 - Cambridge, Cambridge United Kingdom

Genetics

AB from Harvard College

01/1997 - Cambridge, Massachusetts United States

Biochemical Sciences

Professional Interests

• Functional genomics of Alzheimer's disease and Parkinson's disease
• Integrative genetic analyses in humans and Drosophila

Professional Statement

Recent advances have made the discovery of genetic susceptibility loci for complex human phenotypes a reality, including nervous system disorders. The critical next step will be to definitively identify the responsible genes and understand their functions in both health and disease. Our research integrates genetic investigation in human subjects and model organisms, with the goal of understanding brain function and aging, and improving the treatment of neurologic disease. We focus on Alzheimer’s disease and Parkinson’s disease, two incurable neurodegenerative disorders and experimental paradigms for the age-dependent failure of brain cognitive and motor control in humans.

Human Genetics: The clinical manifestation of neurodegenerative disease is the culmination of a multi-tiered pathogenic cascade that evolves over decades—understanding how genetic variants impact this causal chain is essential. Although 2 percent of the population over age 65 are clinically diagnosed with Parkinson’s disease, the defining pathology of disease (alpha-synuclein Lewy bodies) is discovered in 20 percent of brains from population-based autopsy studies. We are, therefore, investigating the impact of genomic variation on directly measured Lewy pathology, neuronal loss in the midbrain substantia nigra, and progressive motor impairment, leveraging human subject cohorts with detailed clinical and pathological data. In complementary investigations, we are deploying biosensor devices to improve detection of Parkinson's-related motor impairment, including the development of quantitative biometric phenotypes for genetic analyses of disease subtypes. We are also performing whole exome sequencing of individuals with familial Parkinson's disease and related disorders, and exploring potential links between inherited pediatric lysosomal and late-onset, adult neurodegenerative diseases.

Drosophila Genetics: Despite the promise of current human genetic methods, such as genome-wide association studies and next generation sequencing, they often fail to definitively identify disease susceptibility genes and variants. We are, therefore, taking advantage of the rapid and powerful genetics available in the fruit fly Drosophila melanogaster in order to accelerate the validation of responsible genes and an understanding of their functions in the nervous system, including for disease pathogenesis. Expression of human amyloid-beta, Tau, or alpha-synuclein proteins in the fly nervous system recapitulates many core features of Alzheimer’s disease and Parkinson’s disease pathogenesis. We are testing candidate human susceptibility genes for functional genetic interactions in these fly models of neurodegeneration. Implicated molecular pathways are probed in greater depth, using both Drosophila and human genetic approaches. Current areas of interest include endolysosomal sorting, RNA metabolism/splicing, neuronal cell adhesion, and synaptic mechanisms of neurodegeneration.

Websites

Selected Publications

• Chibnik LB, Shulman JM, Leurgans SE, Schneider JA, Wilson RS, Tran D, Aubin C, Buchman AS, Heward CB, Myers AJ, Hardy JA, Huentelman MJ, Corneveaux JJ, Reiman EM, Evans DA, Bennett DA, De Jager PL "CR1 is associated with amyloid plaque burden and age-related cognitive decline.." Ann. Neurol..2011/March;69(3):560-9. Pubmed PMID: 21391232
• Treusch S, Hamamichi S, Goodman JL, Matlack KE, Chung CY, Baru V, Shulman JM, Parrado A, Bevis BJ, Valastyan JS, Han H, Lindhagen-Persson M, Reiman EM, Evans DA, Bennett DA, Olofsson A, Dejager PL, Tanzi RE, Caldwell KA, Caldwell GA, Lindquist S "Functional links between aß toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast.." Science.2011/December2;334(6060):1241-5. Pubmed PMID: 22033521
• Shulman JM, Chipendo P, Chibnik LB, Aubin C, Tran D, Keenan BT, Kramer PL, Schneider JA, Bennett DA, Feany MB, De Jager PL "Functional screening of Alzheimer pathology genome-wide association signals in Drosophila.." Am. J. Hum. Genet..2011/February11;88(2):232-8. Pubmed PMID: 21295279
• Shulman JM, Feany MB "Genetic modifiers of tauopathy in Drosophila.." Genetics.2003/November;165(3):1233-42. Pubmed PMID: 14668378