About the Davis Lab

Our laboratory, (Davis and Ronaldson Labs), continue their highly cited and award winning drug delivery program, continuously funded by N.I.H. since 1981, by studying key mechanisms involved in delivering therapeutics across the blood-brain barrier (BBB) to the central nervous system (CNS) in neurological disease states. We have recently discovered specific drug transporters, OATP and P-gp, altered by CNS pathologies which can be targeted to enhance drug delivery. We published earlier the pivotal finding that hypoxia / reoxygenation - stroke alters paracellular permeability and tight junction protein disruption at the BBB. These reports described hypoxic stress leading to significant alterations in BBB permeability that can be reversed by Tempol, a free radical scavenger, suggesting oxidative stress is altering BBB functional integrity during a pathophysiological insult such as stroke.  Additionally, we were the first lab to report that peripheral inflammatory pain has significant effects on BBB structure and function characterized by changes in oligomeric assemblies of the key BBB tight junction proteins occludin and claudin-5, and altered functional expression and trafficking of the drug efflux transporter P-glycoprotein. These disruptions in BBB functional integrity lead to "leak" in opioid analgesic drug delivery such as codeine and morphine, to the CNS. Our most recent and exciting work has demonstrated changes in BBB functional integrity and the OATP transporter, regulated, in part, by altered transforming growth factor-beta (TGF-β) signaling. We now report that the neuroprotective effects of atorvastatin in acute ischemic stroke requires OATP-mediated transport at the blood-brain barrier and therefore OATP-Mediated Transport is central to statin therapy.   Dr Tom Davis Complete CV.cvtpd2023.docx