Amir Kucharski

MSTP in PhD Training

Program: Molecular Cell Biology

Current advisor: Regis J. O`Keefe, MD, PhD

Undergraduate university: University of Kentucky, 2017

Enrollment year: 2017

Research summary
Understanding and targeting the role of Abat in the progression and treatment of osteoarthritis.

Osteoarthritis (OA) is a biomechanical disease with a chronic, low-grade inflammatory component. Our lab has previously shown that this inflammation leads to a downregulation of DNA methyltransferase 3B (DNMT3B), resulting in pathologic DNA methylation patterns. A non-biased screening of genes affected revealed GABA-transaminase (ABAT) to be among the most significantly upregulated with DNMT3B LOF. A follow up study showed ABAT overexpression to be a driver of disease, while ABAT inhibition with Vigabatrin attenuated OA progression. My project’s major aims are to: 1. Understand the connection between ABAT expression, GABA metabolism and signaling, and chondrocyte homeostasis; and 2. Deliver a peptide-siRNA polyplex via intra-articular injection in order to reduce ABAT levels and attenuate/reverse OA.

Graduate publications
Tsen SD, Springer LE, Sharmah Gautam K, Tang R, Liang K, Sudlow G, Kucharski A, Pham CTN, Achilefu S. 2021 Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes. Arthritis Res Ther, 23(1):265. PMCID: PMC8543875