BME Seminar: Patrick T. Ronaldson
Monday, March 18, 2024 - 12:00 p.m.
Patrick T. Ronaldson, PhD, FAAPS
Chair, Neuroscience GIDP
Professor, Department of Pharmacology
College of Medicine
University of Arizona
"Endogenous Blood-Brain Barrier Transporters are Critical Determinants of Neuroprotective Drug Efficacy in Ischemic Stroke"
Keating 103
Zoom link | Password: BearDown
Hosts: Dr. Mario Romero-Ortega and Dr. Shang Song
(Instructor permission required for enrolled students to attend via Zoom)
Persons with a disability may request a reasonable accommodation by contacting the Disability Resource Center at 621-3268 (V/TTY).
Abstract: Stroke is the fifth leading cause of death in the United States. Available treatment strategies for stroke are focused on rescuing injured brain tissue that surrounds the infarction core (i.e., the ischemic penumbra). These include pharmacotherapy (i.e., thrombolysis with recombinant tissue plasminogen activator (r-tPA) or off-label use of Tenecteplase) and surgical interventions via endovascular thrombectomy (EVT). These therapies promote reperfusion of ischemic brain tissue; however, reperfusion therapies are associated with exacerbation of neuronal injury and/or death. Additionally, both r-tPA therapy and EVT have a limited therapeutic window of 4 to 6 hours from the onset of stroke due to risk of hemorrhagic transformation. Therefore, there is an unmet clinical need for neuroprotective therapies that can protect neuronal tissue and promote repair in stroke. To date, drug discovery for stroke has been challenging as indicated by poor translatability of compounds from preclinical studies to successful clinical trials. In contrast, some drugs (i.e., 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (i.e., statins) have utility in improving functional neurological outcomes in stroke patients. This property indicates that statins are efficiently delivered across the blood-brain barrier (BBB). In vivo studies conducted in our laboratory have uncovered specific transport mechanisms that enable these drugs to be delivered from the systemic circulation into brain tissue: transport via endogenous BBB uptake transporters organic anion transporting polypeptide 1a4 (Oatp1a4). We have shown that these transporters are required for statins to exert neuroprotective effects in the ischemic brain, even in the setting of the increased paracellular “leak” that occurs in response to ischemia/reperfusion injury. This seminar will highlight our current work on BBB transporters in stroke. As such, we will demonstrate that the BBB is not “open and shut” following an ischemic insult, observations that providing a platform for development of novel treatment strategies for ischemic stroke.
Bio: Patrick T. Ronaldson, PhD, FAAPS, is a professor in the Department of Pharmacology and the chair of Graduate Interdisciplinary Program in Neuroscience at the University of Arizona. His research achievements in blood-brain barrier physiology, transporter pharmacology, drug delivery technologies, and pharmacokinetics are internationally recognized. A highlight of Dr. Ronaldson’s work in the pharmaceutical sciences is the novel observation that transporters are essential determinants of brain drug uptake and efficacy in diseases where blood-brain barrier integrity is known to be compromised such as ischemic stroke. Dr. Ronaldson’s work has resulted in more than 50 peer-reviewed publications and 8 book chapters. Additionally, his laboratory has an outstanding reputation for scientific collaboration and mentorship. This has resulted in Dr. Ronaldson’s development of an excellent training environment for the next generation of blood-brain barrier and transporter scientists. These accomplishments in research and mentorship resulted in his elevation to fellow status at the American Association of Pharmaceutical Scientists (AAPS). Dr. Ronaldson has served as chair of multiple peer review committees at the National Institutes of Health, is a member of the Academy
of Medical Education Scholars (AMES), and has led multiple volunteer committees at AAPS.