The Department of Physiology continues its seminar series for academic year 2020-2021 by welcoming Dr. Paul DeCaen, Assistant Professor of Pharmacology at Northwestern University’s Feinberg School of Medicine in Chicago, Illinois. Dr. DeCaen will present his seminar titled “Molecular dysregulation PKD2 channels in ADPKD” TODAY, Thursday, December 10, from 3:30-4:30pm.
Dr. DeCaen was awarded an NIH R01 grant for his project “Impacts of Finger 1 variants on PKD2 ion channel function in the primary cilia,” and he will discuss his current research which aims to revolutionize our understanding of molecular mechanisms which control ion channel function and the pathology of ciliopathies in this seminar.
Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that causes progressive renal failure in midlife. Forms of ADPKD can be caused by variants PKD2 (polycystin-2), which encodes for the PKD2 ion channel. Despite our strong understanding of the genetic basis, there is no drug cure for ADPKD and do not know how ADPKD-variants alter PKD2 function. These 20-year-old questions remain outstanding because PKD2 localizes to primary cilium—an antenna-like organelle that requires innovative tools to study. Recently, our lab achieved the first heterologous and native electrophysiological characterization of PKD2 in the primary cilia membrane. With our collaborators, we also published normal and variant PKD2 high-resolution cryo-EM structures. This work has provided snapshots of the open and closed channel states, and molecular blueprint for prototypic drug design. Based on these observations, we propose mechanistic hypotheses regarding the impact variants found within specific structural domains, and how drug binding might modify channel activity as a therapeutic strategy for ADPKD.
If you are interested in tuning in to this seminar, please contact Dr. Nathan Tipton (email@example.com) for Zoom call-in particulars.
We look forward to seeing everyone this afternoon at 3:30pm!