Joshua
Middle Name
M
Shulman, M.D., Ph.D.
Middle Name
M
Picture
Positions
- Professor
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Neurology, Neuroscience, and Molecular & Human Genetics
Baylor College of Medicine
- Investigator
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Jan and Dan Duncan Neurological Research Institute
Texas Children's Hospital
Addresses
- Parkinson's Disease Center and Movement Disorders Clinic (Clinic)
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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
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
- Movement Disorders
- Neurogenetics
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 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 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 understand relevant mechanisms in nervous system health and disease. 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.
Websites
VIICTR Research Database
Selected Publications
- 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.
- Johnson ECB, Dammer EB, Duong DM, Ping L, Zhou M, (...), Shulman JM, Lah JJ, Levey AI, Seyfried NT "Large-scale Proteomic Analysis of Alzheimer’s Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation.." Nat. Med. 2020;26:769-780.
- 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.
- Guo C, Jeong HH, Hsieh YC, Klein HU, Bennett DA, De Jager PL, Liu Z, Shulman JM "Tau Activates Transposable Elements in Alzheimer's Disease.." Cell Rep. 2018;23:2874-2880.
- Jansen IE, Ye H, Heetveld S, Lechler MC, (...), International Parkinson’s Disease Genetics Consortium (IPGDC), Morris HR, Brice A, Singleton AB, David DC, Nollen EA, Jain S, Shulman JM, Heutink P "Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.." Genome Biol. 2017;18:22.
- 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.
- Chouhan AK, Guo C, Hsieh YC, Ye H, Senturk M, Zuo Z, Li Y, Chatterjee S, Botas J, Jackson GR, Bellen HJ, Shulman JM "Uncoupling neuronal death and dysfunction in Drosophila models of neurodegenerative disease.." Acta Neuropathol Commun. 2016;4:62.
- Farlow JL, Robak LA, Hetrick K, Bowling K, Boerwinkle E, Coban-Akdemir ZH, Gambin T, Gibbs RA, Gu S, Jain P, Jankovic J, Jhangiani S, Kaw K, Lai D, Lin H, Ling H, Liu Y, Lupski JR, Muzny D, Porter P, Pugh E, White J, Doheny K, Myers RM, Shulman JM, et al. "Whole-Exome Sequencing in Familial Parkinson Disease.." JAMA Neurol. 2016;73:68-75.
- Jakobsdottir J, van der Lee SJ, Bis JC, Chouraki V, Li-Kroeger D, Yamamoto S, (...), Seshadri S, Shulman JM, Gudnason V, van Duijn CM "Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease." PLoS Genet. 2016;12:e1006327..
- Ali YO, Allen HM, Yu L, Li-Kroeger D, Bakhshizadehmahmoudi D, Hatcher A, McCabe C, Xu J, Bjorklund N, Taglialatela G, Bennett DA, De Jager PL, Shulman JM, Bellen HJ, Lu HC "NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies.." PLoS Biol. 2016;14:e1002472.
- Shulman JM "Drosophila and experimental neurology in the post-genomic era." Exp Neurol. 2015 Dec;274:4-13. Pubmed PMID: 25814441
- Shulman JM, Imboywa S, Giagtzoglou N, Powers MP, Hu Y, Devenport D, Chipendo P, Chibnik LB, Diamond A, Perrimon N, Brown NH, De Jager PL, Feany MB "Functional screening in Drosophila identifies Alzheimer's disease susceptibility genes and implicates Tau-mediated mechanisms." Hum Mol Genet. 2014 Feb 15;23:870-7. Pubmed PMID: 24067533
- Shulman JM, Yu L, Buchman AS, Evans DA, Schneider JA, Bennett DA, De Jager PL "Association of Parkinson disease risk loci with mild parkinsonian signs in older persons." JAMA Neurol. 2014 Apr;71:429-35. Pubmed PMID: 24514572
- Haelterman NA, Yoon WH, Sandoval H, Jaiswal M, Shulman JM, Bellen HJ "A mitocentric view of Parkinson's disease." Annu Rev Neurosci. 2014;37:137-59. Pubmed PMID: 24821430
- 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
- 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
- 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
- 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
- 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, De Jager PL, Feany MB "Parkinson's disease: genetics and pathogenesis.." Annu Rev Pathol. 2011 Feb 28;6:193-222. Pubmed PMID: 21034221
- 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, 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
- Shulman JM, Feany MB "Genetic modifiers of tauopathy in Drosophila.." Genetics. 2003 Nov;165(3):1233-42. Pubmed PMID: 14668378
- 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
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