Gregory Pazour, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Program in Molecular Medicine

Other Affiliation(s):
   Cell Dynamics Group
   Interdisciplinary Graduate Program
   Physiology

Function of the Mammalian Primary Cilium and Mechanisms of Eukaryotic Ciliary Assembly

We are interested in the function of primary cilia.  These organelles play vital roles in the development of mammals and in the etiology of diseases such as polycystic kidney disease and blindness.  Our work combines in vitro cell culture studies with mutant mouse models to understand the role of cilia in controlling kidney architecture and the formation of the photoreceptor outer segment.

In the kidney, the epithelial cells lining the ducts and tubules of the nephron have prominent primary cilia extending from their surface into the lumen of the duct.  We showed that the Tg737 mouse model of polycystic kidney disease has defects in these cilia.  The gene mutated in the Tg737 mouse encodes the IFT88 subunit of the intraflagellar transport (IFT) particle. IFT is bidirectional movement along the length of cilia that is thought to carry materials needed for assembly and maintenance of cilia and flagella.

       Figure 1.               

It is thought that primary cilia on kidney epithelial and other cells are sensory organelles that monitor the extracellular environment.  Information perceived by cilia control aspects of cell physiology including proliferation and differentiation, along with cellular and organ architecture.  We are currently focused on understanding how cilia function to maintain the normal architecture of the kidney and prevent cystic disease.  To do this we have created a floxed allele of the gene encoding the IFT20 subunit of the IFT particle.  Deletion of this gene in the kidney causes severe polycystic kidney disease.  During the development of cystic disease in this animal, the collection ducts (labeled green in Figure 2) greatly enlarge and disrupt the architecture of the kidney.   

        Figure 2.            

Another focus of the laboratory is to understand how the outer segments of vertebrate photoreceptor rod and cone cells are assembled.  These structures are highly modified cilia and require intraflagellar transport for assembly.  Defects in transport cause progressive retinal degeneration eventually leading to blindness.  To study the role of intraflagellar transport in photoreceptor outer segment assembly, we deleted IFT20 specifically in cone cells.  This initially causes photopigments to accumulate in the cell body and causes cone cell degeneration, eventually destroying all the cones.  Rod cells are not affected in these animals.  In Figure 3 cone outer segments are labeled green, rod outer segments are labeled red, and photoreceptor nuclei are labeled blue.  

Figure 3.         

Representative Publications

See http://users.umassmed.edu/gregory.pazour/for a complete list.

Jonassen, J., SanAgustin, J., Follit, J.A. and Pazour, G.J.. 2008. “Deletion of IFT20 in the Mouse Kidney Causes Misorientation of the Mitotic Spindle and Cystic Kidney Disease”  J. Cell Biol. in press.

Merchant et al., 2007 “The Chlamydomonas genome reveals the evolution of key animal and plant functions" Science. 318:245-50.

Follit, J.A., Tuft, R.A., Fogarty, K.E., and Pazour, G.J. 2006.  The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly.   Mol. Biol. Cell, 17:3781-3792.

Pazour, G.J., Agrin, N., Leszyk, J., and Witman, G.B. 2005.  Proteomic characterization of a eukaryotic cilium. J. Cell Biol. 170:103-113.

Pazour, G.J., Baker, S., Deane, J., Cole, D.G., Dickert, B.L., Rosenbaum, J.L., Witman, G.B., and Besharse, J. 2002. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J. Cell Biol. 157: 103-113.

Pazour, G.J., San Agustin, J.T., Follit, J.A., Rosenbaum, J.L., and Witman, G.B., 2002. Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr. Biol. 12: 3778-380.

Pazour, G.J., Dickert, B.L., Vucica, Y., Seeley, E.S., Rosenbaum, J.L., Witman, G.B. and Cole, D.G. 2000. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene Tg737, are required for assembly of cilia and flagella. J. Cell Biol. 151: 709-718.

Pazour, G.J., Dickert, B.L., and Witman, G.B. 1999. The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. J. Cell Biol. 144: 473-481

Pazour, G.J., Wilkerson, C.G., and Witman, G.B. 1998. A dynein light chain is essential for the retrograde particle movement of intraflagellar transport (IFT). J. Cell Biol. 141: 979-992.

Pazour, G.J., Sineschekov, O.A., and Witman, G.B. 1995. Mutational analysis of the phototransduction pathway of Chlamydomonas reinhardtii. J. Cell Biol. 131: 427-440.

Potential Rotation Projects

Rotation projects in my laboratory will involve questions of how cilia are assembled and the function these organelles play in mammals. 

Projects vary depending on ongoing work in the laboratory and interests of the rotation student. Rotations in my laboratory can give students exposure to a range of techniques from mouse breeding and histological analysis of mouse tissues to mammalian cell culture and other cell biological techniques. 

Academic Background

Ph.D., 1991, University of Minnesota

Office: B2-213
Phone: 508-856-8078
Fax: 508-856-5612
E-mail: Gregory.Pazour@umassmed.edu
Keywords: Genetic Systems, Cell Biology, Intracellular Trafficking

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