March 28, 2023 11:00 am
- 12:00 pm
Vladimir Yarov-Yarovoy, Ph.D.

Vladimir Yarov-Yarovoy, PhD
Dept. of Physiology and Membrane Biology, UC Davis

Tuesday Mar. 28, 2023
Seminar 11 a.m. – Noon
Classroom Building CR 170

Rational Design of Novel Ion Channel Modulators

The voltage-gated sodium NaV1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human NaV1.7 activation. We used available structural and experimental data to guide Rosetta design of potent and selective ProTx-II-based peptide inhibitors of human NaV1.7 channels. Functional testing of designed peptides using electrophysiology identified lead peptides with nanomolar potency for hNaV1.7 and more than 1,000-fold selectivity over human NaV1.1, NaV1.3, NaV1.4, NaV1.5, NaV1.8, and NaV1.9 channels. Our lead peptide inhibits NaV1.7 currents in mouse and human sensory neurons and shows efficacy in rat models of chronic and thermal pain when administered intrathecally. Rationally-designed peptide inhibitors of human NaV1.7 channels have
transformative potential to define a new class of biologics to treat pain.

About the Speaker
Dr. Vladimir Yarov-Yarovoy earned an M.S. Degree in Physics at the Moscow State University in Moscow, Russia, and then Ph.D. Degree in Biochemistry and Molecular Biology at the Oregon Health Science University in Portland, Oregon. Dr. Yarov-Yarovoy was a postdoctoral fellow in Biophysics and Computational Biology and then a Research Assistant Professor in the Department of Pharmacology at the University of Washington in Seattle, Washington. He joined UC Davis as an Assistant Professor in Physiology and Membrane Biology in 2011 and became a full Professor in 2020.


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