Dr. Travis Jackson recently received a Scientist Development Grant from the American Heart Association, National Affiliate, to continue his project, “Pharmacological inhibitors of PHLPP1: Novel therapies to treat brain injury after cardiac arrest.”
Dr. Jackson’s four-year study will test if small-molecule PHLPP1 inhibitors ameliorate ischemia-induced neuronal death. Last year, Dr. Jackson and colleagues reported in the Journal of Pharmacology and Experimental Therapeutics that several novel PHLPP1 inhibitors reduced neuronal injury in vitro but lack optimal pharmacology for in vivo translation - due to undesirable chemistry including unlikeliness to cross the blood brain barrier (BBB). His newly funded study will test a series of candidate PHLPP1 inhibitors predicted to cross the BBB. Neuroprotective effects will be evaluated using a clinically relevant rat model of ventricular fibrillation CA to induce brain ischemia.
“If results are positive,” Dr. Jackson says, “we might find the first translatable PHLPP1 inhibitor to target this mechanism in vivo.” Blocking this pro-death signaling pathway after injury could improve neurologic outcomes after cardiac arrest as well as in other types of brain injuries.
Dr. Jackson is a Research Assistant Professor in the University of Pittsburgh School of Medicine, and Associate Director of Cell Signaling in the Safar Center for Resuscitation Research.