Matthew Hirsch, PhD
Associate Professor, Ophthalmology
Research Associate Professor, Microbiology & Immunology
About
Matt left his home state of Pennsylvania to “Wild and Wonderful” West Virginia University where he graduated Phi Beta Kappa and summa cum laude in Biology. Matt elucidated the role of the stress response regulator, RpoS, in E. coli and Salmonella to obtain his PhD under the guidance of the classical geneticist Tom Elliott. Then, Matt did a post-doctorate research fellowship with Jude Samulski at the University of North Carolina Gene Therapy Center and found it difficult to leave the beautiful weather and AAV community in Chapel Hill. Currently, Matt is an associate professor at UNC in Ophthalmology with a joint appointment in Microbiology. Matt enjoys bench work elucidating the concept of “stemness” using AAV biology, learning from his dog, and scientific discussion around a campfire.
Some current projects in the lab focus on the following areas.
Synthetic Inverted Terminal Repeats
We have a panel of rationally designed ITRs that alter nearly all aspects of AAV vector biology including production, transduction efficiency, and the cellular responses to the vector. Additionally, we have an mutant AAV ITR library that is being evaluated for increased AAV vector production and enhanced gene editing. The ITR engineering revolution for AAV gene therapy is just around the corner!
Ocular Therapeutics
One drug one disease…AAV vector applications in the anterior eye have been largely overlooked. Therefore we are addressing that deficit towards improved vision in patients with a variety of ocular diseases such as various lysosomal storage disorders and congenital hereditary endothelial dystrophy.
One drug many diseases…Beyond single disease therapeutics, we are pursuing a “One for Many” approach based on HLA-G, perhaps the body’s most power immune suppressant that plays a natural role in the establishment of ocular immune privilege. By inhibiting angiogenesis and the immune system in general, potential applications of HLA-G ocular gene therapy include prevention of corneal graft rejection, age-related macular degeneration, and diabetic retinopathy. Additional applications of the same drug include the prevention of immunological rejection of other organs and perhaps as a treatment fo immunological diseases in general.
DNA damage response, stemness, differentiation, and cancers
The AAV ITR induces unique DNA damage responses in manner that correlates to specific states of cellular differentiation. Our investigations into the ITR-induced cellular responses in pluri- and multi-potent cells may shed light on evolution, improved safety profile of AAV vectors, and perhaps novel cancer therapeutics.
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Undergradute
Biology
West Virginia University -
Doctor of Philosophy
Bacterial Genetics
West Virginia University -
Post-Doctorate
Jude Samulski Lab
UNC Gene Therapy Center
University of North Carolina at Chapel Hill