Amir Kucharski (MSTP in PhD training)

  • Milwaukee, WI

  • University of Kentucky (2017)

  • Molecular Cell Biology

  • Regis J. O`Keefe, M.D., Ph.D.

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

  • akucharski@wustl.edu

Research

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.

Last Updated: 9/17/2019 8:59:14 PM

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