Professor, BIO5 Institute
Professor, Neuroscience - GIDP
Professor, Physiological Sciences - GIDP
The Davis Laboratory has spent the past 35 years actively studying the challenges of central nervous system (CNS) drug delivery in disease states. Their scientific and research focus remains the same today, to develop “state of the art” methods/procedures/tools/models for quantifying/studying the in vivo integrity and regulation of the blood brain barrier/neurovascular unit (BBB/NVU), and specific multi-drug transporters such as P-glycoprotein (mdr1a;PgP), as altered by pathological disease states associated with brain injury (stroke/hypoxia) and acute versus chronic pain (inflammatory, migraine and cancer pain).
They remain dedicated to their mission of maintaining the strongest basic science research program in drug delivery while educating and training undergraduate, graduate and post-doctoral fellows to advance their chosen field.
In the course of their research into the molecular, biochemical and pathophysiological mechanisms associated with maintenance and disruption of the blood-brain barrier/neurovascular unit and endothelial cell tight junction proteins and transporters, they have been cited by their peers for “paradigm shifting” discoveries and meritorious mentoring of the “next generation” of researchers. The BBB and NVU remain the most significant challenge to CNS drug development from the past century. This fact drives the passion of their students and colleagues. they understand that progress in preventing, diagnosing, or treating diseases of the CNS depends upon understanding the BBB and NVU. It is often stated, “if they cannot get the drug into the brain they cannot treat a disease of the brain”.
As BBB/NVU investigators they have a unique perspective, and responsibility, to address a critical priority; that after a century of developing and testing CNS therapeutics, pharmaceutical and biotech companies remain frustrated at the enormity of problems associated with delivering drugs to the CNS. they welcome this challenge and work every day to meet it.
Our laboratory continues its 35-year N.I.H. collaborative biodistribution research program by characterizing the specific cellular mechanisms involved in delivering drugs across the blood-brain barrier (BBB) to the C.N.S. , in pathological disease states. We have discovered specific drug transporters that can be targeted to enhance drug delivery to the brain. We also are studying the effect of hypoxia/aglycemia and pain on brain endothelial cell permeability and transporter protein trafficking at the blood-brain barrier with an ongoing 20 year research program funded by the N.I.N.D.S. of the N.I.H. We have shown that short-term hypoxia/aglycemia and pain leads to significant endothelial transporter protein alterations and tight junction protein changes which can be altered by specific drugs used to treat these pathologies. This work has significant consequences to the field of stroke research. Our latest work focuses on the multi-drug resistant transporter , P- glycoprotein (P-gp) , where we have identified how P-gp is trafficked and modulated by pain at the BBB. P-gp is a major efflux transporter of cancer drugs used to treat brain cancer.