Research Programs

Departmental research activities address a broad spectrum of neurological disorders including Alzheimer’s disease, autism, epilepsy, dystonia and other movement disorders, musculoskeletal trauma, Parkinson’s disease, and stroke.

Age-related neurodegenerative diseases constitute a major focus, involving the study of basic mechanisms and interventions, including gene therapies, in mouse models of Alzheimer’s and Parkinson’s diseases. Investigations targeting brain gangliosides (Dr. McDonald) use genetic and dietary therapies to modulate their levels, showing benefits of increased GM1 ganglioside to improve memory and reduce pathology. Mechanisms involving DNA damage and inflammation (Dr. Khan) represent another area of investigation in these disease models, as well as in brain trauma. His work also seeks to apply gene therapy with tau antisense oligonucleotides in Alzheimer’s models.

Movement disorders, particularly dystonia, present another field of interest. A bank of DNA and RNA samples from thousands of patients with dystonia and other disorders provides a resource for the mapping and cloning of disease-relevant genes (Dr. Xiao), and mutant mouse and rat models facilitate the characterization of brain circuitry and mechanisms underlying their pathogenesis. The Dyt1 mouse model is being used to investigate impacts of the gut microbiome on dystonia (Dr. Khan).

Studies in fruit flies and human dental pulp stem cells (Dr. Reiter) address the molecular genetics of rare syndromes on the autism spectrum. Seizures associated with Duplication 15q are investigated using a Drosophila model of the syndrome for proteomic and drug testing studies. A human stem cell collection, representing over 200 individuals and 14 neurogenetic syndromes, is currently being applied to characterize circadian defects in Prader-Willi and Schaff-Yang syndrome neurons, as well as to study Angelman syndrome and other disorders.[EW1] 

Stroke studies (Dr. Nowak) involve rat and mouse models, with the present emphasis on identifying genetic factors underlying differences in stroke vulnerability among closely related mouse substrains. These can introduce significant confound in studies comparing genetically modified mice on different backgrounds and could potentially prove relevant to human disease.

Research with direct clinical relevance (Dr. Talbot) focuses on musculoskeletal injuries in military populations, testing the benefits of nonsurgical and non-pharmacologic interventions (e.g., rehabilitative therapies, including exercise) that can be applied in limited-resource environments. Results suggest that each may yield positive benefits and that effects of a combined multimodal program may be more than additive.

Faculty