Research Interest

Cilia are microtubule based structures that can be motile or immotile, the latter being referred to as primary cilia. In contrast to motile cilia, such as those found on epithelia of the trachea, the importance of the primary cilium is relatively undefined despite their presence on most mammalian cells. Cilia are extremely complex organelles which are devoid of ribosomes, thus, proteins required for cilia assembly, maintenance, and signaling must be imported into the cilium. This occurs through a microtubule-based transport system called intraflagellar transport (IFT). Proteins involved in IFT concentrate around the basal body at the base of the cilium and assemble into complexes (IFT particles) which are moved up the cilium by a kinesin and returned by a cytoplasmic dynein. The IFT particle is thought to mediate the transport of cargo into the cilium as well as to deliver signals initiated in the cilium to the cytosol. Although the primary cilium was once thought to be a vestigial organelle, recent studies have uncovered that cilia in mammals are required for viability and that dysfunction of the cilium is associated with a large number of developmental abnormalities and disease pathologies. This now includes obesity, cystic kidney, liver, and pancreatic diseases, hydrocephalus, skin and hair follicle abnormalities, random left-right body access specification, and skeletal defects. Although studies in mice and humans now indicate that cilia are critically important organelles, the functions of cilia and the pathways in which they are required remains largely unknown. Addressing these issues is the major focus of my group’s research. Our studies utilize comparative approaches in both mouse and C. elegans to investigate four major interrelated themes:

1. What roles do cilia play in regulating signaling pathways?
2. What are the functions of cilia in embryogenesis and tissues physiology in postnatal life?
3. How does cilia dysfunction cause disease and developmental abnormalities?
4. What proteins localize in cilia, how are they targeted to this organelle, and what role do they play in cilia assembly or signaling activities?

Lab Members:
Svetlana Masyukova
Nicolas Berbari
Jon Lehman
Corey Williams
Neeraj Sharma
Zak Kosan
Amber O’Connor
Venus Childress
Mandy Croyle

List of Techniques Used:
Animal models of disease
Transgenic mice and worms
Mouse chimera analysis
Immunohistology, in situ, and immunofluorescence analysis
Time lapse live cell imaging
EM and light microscopy
In vitro embryo culture
Microinjection
Protein biochemistry
Western and Northern blot analysis
Protein interaction studies (yeast two-hybrid, coimmunoprecipitation, FRET)
Mutagenesis screens

Title of Possible Projects:
Signaling activity of renal cilium
Cilia and pattering of the mammalian skeleton
Regulation of renal cilia assembly
Protein targeting to cilia
The role of cilia in developmentally important signaling pathways
Genetics of sensory cilia formation and signaling in C. elegans

Biography