Life Sciences Seminar: External Speaker, Dr. Gregory J. Pazour, “Cilia, Little Organelles with Big Roles in Development and Disease”

Gregory J. Pazour, Ph.D.

Professor, Program in Molecular Medicine

University of Massachusetts Chan Medical School

Hosted by: Assistant Professor Shane Mclnally

Tuesday, April 29, 12:00 pm

Gateway 1002 ~ Pizza will be served

Abstract: 

Cilia play crucial roles in motility and sensory functions across eukaryotes. In humans, defects in motility cause respiratory disease, male infertility, and cardiac malformations due to disruptions in the left-right body axis. Sensory defects lead to blindness, anosmia, and contribute to conditions like polycystic kidney disease and obesity. During development, sensory cilia are vital, and defects cause structural birth defects in the skeleton, brain, heart, lungs, kidneys, and other organs. These developmental defects are strongly linked to disruption of the Hedgehog pathway, which is organized in the primary cilium. In the absence of a Hedgehog ligand, the Ptch1 receptor on the ciliary membrane suppresses signaling. Hedgehog ligand binding to Ptch1 inhibits its suppressive activity and causes it to exit the cilium. This promotes the ciliary accumulation and activation of the Smo receptor. Activated Smo in turn promotes the accumulation of Gli transcription factors at the ciliary tip, where they are modified to become transcriptional activators. These dynamic movements are powered by the intraflagellar transport (IFT) system. In addition to driving the dynamics of Hedgehog signaling, IFT is responsible for assembling most types of cilia. During IFT, large protein complexes called IFT particles are transported along the ciliary microtubules by kinesin-2 and dynein-2 motors. These particles serve as motor adaptors facilitating the transport of 1000 or more ciliary components from the site of synthesis in the cell body to the cilium.

Bio: 

Dr. Gregory J Pazour is currently a professor of molecular medicine at the University of Massachusetts Chan Medical School. He earned his Ph.D. from the University of Minnesota, where he studied the plant pathogen Agrobacterium. This was followed by postdoctoral studies at the Worcester Foundation for Biomedical Research, where he made the unexpected connection between cilia in the green alga Chlamydomonas and polycystic kidney disease. This work, published in 2000, demonstrated that a mouse polycystic kidney disease gene was required for ciliary assembly and that ciliary defects lead to kidney cyst formation. In 2002, he showed that the gene product of a major human polycystic kidney disease gene (PKD2) localized to cilia explaining why cilia were critical to preventing cyst formation. These findings dramatically shifted the focus of polycystic kidney disease research where it is now recognized that cilia are central to the disease. Furthermore, this work opened a new field of research into the function of cilia in development and in homeostasis. These contributions have been recognized by the Kaplan Prize from the International Society for Nephrology, the Bensley Award from the American Association of Anatomists and being named a Porter Fellow by the Keith Porter Endowment for Cell Biology as well as being named a Fellow of the American Society for Cell Biology. His current work focuses on understanding the mechanisms of ciliary assembly and the role that cilia play in mammalian health and development. In particular, the Pazour group is interested in the function of the intraflagellar transport proteins and the role that cilia play in development and in degenerative diseases like blindness and polycystic kidney disease.