Positions
- Professor
-
Neurology, Neuroscience, and Molecular & Human Genetics
ÌÇÐÄÊÓƵ of Medicine
- 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)
-
ÌÇÐÄÊÓƵ of Medicine 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.
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
Dr. Shulman's Bibliography
Comprehensive list of publications and presentations
VIICTR Research Database
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.
to edit your profile