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Neurology

Houston, Texas

The Cullen Building at Baylor College of Medicine.
Department of Neurology
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Joshua M. Shulman, M.D., Ph.D.

Assistant Professor of Neurology and Molecular & Human Genetics [view Genetics profile]

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

Principal Investigator, Laboratory for Integrative Functional Genomics

Clinical Service Area

Neurology

Specialty

Neurogenetics
Parkinson's Disease
Movement Disorders

Clinic Appointments

713-798-7438

Consult

713-798-7438

Medical School

M.D., Harvard Medical School & M.I.T. Health Sciences and Technology, Boston, Mass.

Graduate School

Ph.D., University of Cambridge, United Kingdom

Internship

Internal Medicine, Massachusetts General Hospital, Boston, Mass.

Residency

Neurology, Brigham and Women's Hospital & Massachusetts General Hospital, Boston, Mass.

Clinical Fellowship

Movement and Memory Disorders, Brigham and Women's Hospital & Massachusetts General Hospital, Boston, Mass.

Post-Doctoral Research Fellowship

Neurogenetics, Brigham and Women's Hospital & Broad Institute of Harvard/M.I.T., Boston, Mass.

Clinic Location

Baylor Neurology
Smith Tower
6550 Fannin, Suite 1801
Houston, Texas 77030

Clinical Interests

Parkinson's disease and related movement disorders

Research Areas

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

Research Interests

Integrative Functional Genomics in Neurodegenerative Disease

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% 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% 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. We also participate in collaborative studies for the functional genetic dissection of Alzheimer's disease, focusing on the responsible neuropathology, amyloid neuritic plaques and Tau neurofibrillary tangles.

Drosophila Genetics

Despite the promise of current human genetic methods, such as genome-wide association studies, they often fail to identify disease susceptibility genes with certainty, instead highlighting broad genomic regions. 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 an understanding of their functions in 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. Our strategy has recently identified cell adhesion converging on the cytoskeleton as likely important for Tau-mediated neurodegeneration and Alzheimer's disease susceptibility, and we are now following up these insights to elucidate the detailed mechanisms.

Contact Information

Joshua M. Shulman, M.D., Ph.D.
Jan and Dan Duncan Neurological Research Institute
1250 Moursund St., Suite N.1150
Houston, Texas 77030

Tel: 832-824-8806
Fax: 832-825-1249
Email:

Journal Publications (Selected out of 37)

  • Buchman AS, Shulman JM, Nag S, Leurgans SE, Arnold SE, Morris MC, et al. Nigral pathology and parkinsonian signs in elders without Parkinson disease. Ann Neurol. 2012;71(2):258-66. [View journal article]
  • 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;33(5):1017 e1-15. [View journal article]
  • Chibnik LB, Shulman JM, Leurgans SE, Schneider JA, Wilson RS, Tran D, et al. CR1 is associated with amyloid plaque burden and age-related cognitive decline. Ann Neurol. 2011;69(3):560-9. [View journal article]
  • Shulman JM, Chipendo P, Chibnik LB, Aubin C, Tran D, Keenan BT, et al. Functional screening of Alzheimer pathology genome-wide association signals in Drosophila. Am J Hum Genet. 2011;88(2):232-8. [View journal article]
  • Shulman JM, De Jager PL, Feany MB. Parkinson's disease: genetics and pathogenesis. Annu Rev Pathol. 2011;6:193-222. [View journal article]
  • Treusch S, Hamamichi S, Goodman JL, Matlack KE, Chung CY, Baru V, et al. Functional links between Abeta toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast. Science. 2011;334(6060):1241-5. [View journal article]
  • 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. [View journal article]
  • Shulman JM, Feany MB. Genetic modifiers of tauopathy in Drosophila. Genetics. 2003;165(3):1233-42. [View journal article]
  • Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J, Hutton M, et al. Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science. 2001;293(5530):711-4. [View journal article]
  • 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;101(4):377-88. [View journal article]

Poster and Platform Presentations (Selected out of 25)

  • Shulman J, Yu L, Buchman A, Evans D, Schneider J, Bennett D, et al. Exploring the impact of Parkinson disease (PD) susceptibility genes in elders without PD. Neurology. 2013;80(Meeting Abstracts 1):S13.006. [Platform Presentation]
  • Shulman JM, Chen K, Keenan BT, Chibnik LB, Thiyyagura P, McCabe C, et al. Genetic susceptibility for amyloid pathology in Alzheimer's disease. Ann Neurol. 2012;72 Suppl 16:S51.
  • Shulman JM, Imboywa S, Diamond AE, Chipendo P, De Jager PL, Feany MB. Integrating human and fly genetics to understand Alzheimer's disease susceptibility. Ann Neurol. 2012;72 Suppl 16:S51.
  • Shulman JM. Genetic analyses of Parkinson's disease endophenotypes. Presented at the Parkinson Study Group (PSG), 26th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinson Disease and Other Movement Disorders in Irving, Texas (May 11, 2012). [Platform Presentation]
  • Shulman JM, Chipendo PI, Chibnik LB, Keenan BT, Tran D, Huentelman MA, et al. Integrating genome-wide association and functional validation to understand susceptibility for Alzeheimer's pathology. Ann Neurol. 2011;70 Suppl 15:S50-1. [Platform Presentation]
  • Shulman JM. What can endophenotypes teach us about Parkinson's disease? Presented at the Michael J. Fox Parkinson's Research Foundation, Genetic Epidemiology of Parkinson's Disease Consortium Meetiing in Evanston, Ill. (Sept. 18-21, 2011). [Oral Presentation]
  • Keenan B, Shulman J, Chibnik L, Corneveaux J, Allen A, Myers A, et al. A candidate causal variant in the CR1 locus. Alzheimers Dement. 2011;7(4 Suppl):S496-S7.
  • Raj T, Shulman J, Chibnik L, Keenan B, Stranger B, Evans D, et al. Alzheimer's disease susceptibility loci: Evidence for natural selection and altered gene expression. Alzheimers Dement. 2011;7(4 Suppl):S183.
  • Sherva R, Tripodis Y, Shulman J, Chibnik L, Crane P, Bennett D, et al. Genetic factors associated with the rate of cognitive decline in Alzheimer's disease. Alzheimers Dement. 2011;7(4 Suppl):S496.
  • Shulman J, Chibnik L, Keenan B, Destefano A, Leurgans S, Wilson R, et al. A genome-wide association scan for episodic memory decline in aging. Alzheimers Dement. 2011;7(4 Suppl):S195.

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