Thursday, January 13, 2022
Dr. Leonidas Tsiokas, PhD
George Lynn Cross Research Professor & Chair
Department of Cell Biology
University of Oklahoma Health Sciences Center
Oklahoma City, OK
“Molecular and Cellular Mechanisms of Renal Cystogenesis”
The Tsiokas laboratory focuses on the molecular mechanisms underlying cystogenesis in the autosomal dominant form of Polycystic Kidney Disease (ADPKD), one of the most common genetic diseases affecting 12.5 million people worldwide. ADPKD is caused by mutations in two genes, PKD1 and PKD2. PKD1 is an atypical G protein coupled receptor complexed with PKD2 (or TRPP2), a Ca2+-permeable ion channel. The Tsiokas laboratory has been studying the following questions: 1) What is the nature of the extracellular stimuli that activate the PKD1/PKD2 receptor/channel complex? 2) What is the molecular make-up of the complex? 3) What are the downstream effectors and cellular processes of the PKD1/PKD2 complex? And, 4) What is the role of the primary cilium in PKD1/PKD2-based signaling? His group has shown that secreted Wnt proteins function as activating ligands of the Polycystin complex and pathogenic PKD1 or PKD2 mutations that abrogate complex formation, compromise cell surface expression of PKD1, or reduce TRPP2 channel activity suppress activation by Wnt ligands. They have recently shown that deletion of PKD1 or PKD2 genes activates the centrosomal integrity/mitotic surveillance pathway causing a delay in ciliary disassembly and persistent activation of cilia-based signaling pathways. These data implicate a cellular function of the Polycystin complex in maintaining centrosomal integrity. The overall goal is to identify the activation mechanisms of the Polycystin complex and relate these mechanisms to cyst formation and expansion.
Please send an email to Dedra Jeffries (email@example.com) if you are interested in the seminar.