Neurology, Neuroscience, and Molecular & Human Genetics
Baylor College of Medicine
Jan and Dan Duncan Neurological Research Institute
Texas Children's Hospital
Jan and Dan Duncan Neurological Research Institute
- Duncan Neurological Research Institute (Lab)
Houston, TX 77030
- Parkinson's Disease Center and Movement Disorders Clinic (Clinic)
Baylor College of Medicine Medical Center
Houston, TX 77030
Phone: (713) 798-2273
- Post-Doctoral Fellowship at Brigham And Women's Hospital
- 01/2012 - Boston, MA United States
- 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
- Internship at Massachusetts General Hospital
- 01/2006 - Boston, MA United States
- MD from Harvard Medical School
- 01/2005 - Boston, MA United States
- PhD from University Of Cambridge
- 01/2000 - Cambridge, Cambridge United Kingdom
- AB from Harvard College
- 01/1997 - Cambridge, Massachusetts United States
- Biochemical Sciences
- Functional genomics of Alzheimer's disease and Parkinson's disease
- Integrative genetic analyses in humans and Drosophila
Professional StatementOur 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.
Comprehensive list of publications and presentations
VIICTR Research Database
- Mangleburg CG, Wu T, Yalamanchili HK, Guo C, Hsieh YC, Duong DM, Dammer EB, De Jager PL, Seyfried NT, Liu Z, Shulman JM "Integrated analysis of the aging brain transcriptome and proteome in tauopathy." Mol Neurodegener.. 2020;15:56. Pubmed PMID: 32993812
- 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.
- Ojelade S, Lee T, Giagtzoglou N, Yu L, Ugur B, (...), Shulman JM "Cindr, the Drosophila homolog of the Alzheimer’s disease risk gene, is required for synaptic transmission and proteostasis.." Cell Rep.. 2019;28:1799-1813.
- Robak LA, Jansen IE, van Rooij J, Uitterlinden AG, Kraaij R, Jankovic J, International Parkinson’s Disease Genomics Consortium (IPDGC), Heutink P, Shulman JM "Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.." Brain. 2017;140:3191-3203.
- 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 Mar;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 Dec 2;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 Feb 11;88(2):232-8. Pubmed PMID: 21295279
- Shulman JM, Feany MB "Genetic modifiers of tauopathy in Drosophila.." Genetics. 2003 Nov;165(3):1233-42. Pubmed PMID: 14668378
- Shulman JM, Chen K, Keenan BT, Chibnik LB, Thiyyagura P, Liu X, Roontive A, Yu L, McCabe C, Patsopoulos NA, Corneveaux JJ, Huentelman MJ, Evans DA, Schneider JA, Reiman EM, De Jager PL, Bennett DA "Genetic Susceptibility for Alzheimer's Disease Neuritic Plaque Pathology.." JAMA Neurol.. 2013;70(9):1150-7. Pubmed PMID: 23836404
- Shulman JM, Chibnik LB, Aubin C, Schneider JA, Bennett DA, De Jager PL "Intermediate phenotypes identify divergent pathways to Alzheimer's disease.." PLoS ONE. 2010;5(6):e11244. Pubmed PMID: 20574532
- Buchman AS, Shulman JM, Nag S, Leurgans SE, Arnold SE, Morris MC, Schneider JA, Bennett DA "Nigral pathology and parkinsonian signs in elders without Parkinson disease.." Ann. Neurol.. 2012 Feb;71(2):258-66. Pubmed PMID: 22367997
- Shulman JM, De Jager PL, Feany MB "Parkinson's disease: genetics and pathogenesis.." Annu Rev Pathol. 2011 Feb 28;6:193-222. Pubmed PMID: 21034221
- Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J, Hutton M, Feany MB "Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles.." Science. 2001 Jul 27;293(5530):711-4. Pubmed PMID: 11408621
- Shulman JM, Benton R, St Johnston D "The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole.." Cell. 2000 May 12;101(4):377-88. Pubmed PMID: 10830165
- De Jager PL, Shulman JM, Chibnik LB, Keenan BT, Raj T, Wilson RS, et al "A genome-wide scan for common variants affecting the rate of age-related cognitive decline." Neurobiol Aging. 2012 May;33(5):1017 e1-15. Pubmed PMID: 22054870
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