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Email

jmshulma@bcm.edu

Positions

Professor

Neurology, Neuroscience, and Molecular & Human Genetics
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Investigator

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

Co-Director

Jan and Dan Duncan Neurological Research Institute

Addresses

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

²ÝÁñÉçÇøÈë¿Ú Medical Center
McNair Campus
Houston, TX 77030
United States
Phone: (713) 798-2273
/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

Our research integrates genetic and genomic 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. We are therefore investigating the impact of genomic variation on directly measured Alzheimer’s and Parkinson’s disease pathology and related biomarkers, including quantitative measures of motor impairment based on assessments with biosensor devices. We are also deploying whole genome sequencing in the Alzheimer’s and Parkinson's disease clinics and returning results to patients and families for precision medicine applications. Lastly, we are actively exploring links between inherited pediatric lysosomal disorders and oligogenic risk for late-onset, adult neurodegenerative diseases.

Drosophila Genetics: Despite the promise of current human genomic strategies, such as genome-wide association studies, next-generation sequencing, and gene expression profiling, they often fail to definitively identify disease causal genes and variants. Therefore, we are 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 understanding of relevant mechanisms. The 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 as well as mouse and human cellular models for translation. Current areas of interest include endolysosomal sorting, RNA metabolism/splicing, neuronal cell adhesion and synaptic mechanisms of neurodegeneration. In order to dissect the dynamic, aging-dependent gene expression changes in brains affected by Alzheimer’s and Parkinson’s disease, we are also generating and analyzing longitudinal, multi-scale omic datasets from fly and mouse models.

Websites

Selected Publications

• Mangleburg CG, Wu T, Yalamanchili HK, Guo C, Hsieh YC, Duong DM, Dammer EB, De Jager PL, Seyfried NT, Liu Z, Shulman JM "." Mol Neurodegener.. 2020;15:56. Pubmed PMID:
• Wan Y-W, Al-Ouran R, Mangleburg CG, (...), Accelerating Medicines Partnership-Alzheimer’s Disease Consortium, Liu Z, Shulman JM, Mangravite L, Logsdon B "Meta-analysis of the Alzheimer’s disease brain transcriptome and functional dissection in mouse models.." Cell Rep.. 2020;32:107908.
• Ye H, Ojelade S, Li-Kroeger D, Zuo Z, Duraine L, He Y, Li Y, Tepass U, Rodal A, Wang L, Bellen HJ, Shulman JM "The retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain.." ELife. 2020;9:e51977.
• Hsieh Y-C, Guo C, Yalamanchili HK, Abreha M, Al-Ouran R, (...), Shulman JM "Tau-mediated disruption of the spliceosome triggers cryptic RNA-splicing and neurodegeneration in Alzheimer’s disease.." Cell Rep.. 2019;29:301-316.e10.