Department of Anatomy and Cell Biology
Ph.D., University of Utah, 2009
Postdoctoral, University of California-San Francisco, 2009-2015
Virtually every cell of the human body has the ability to sense external stimuli. For example, photoreceptors in the eye sense light, epithelial cells in the kidney sense fluid flow and neurons in the olfactory system sense odorants. In each of these cells, the very different types of signals are captured using the same structure, called the cilium. The cilium, a microtubule based protrusion, functions as an antenna to transduce signals into a cellular response. Our lab studies how cilia are built and maintained.
Because the ciliary structure is so well conserved across cell types, a single mutation in a ciliary gene can have a broad range of phenotypes including retinal degeneration, polycystic kidney disease, obesity, diabetes, polydactyly (extra fingers/toes), cognitive impairment and infertility. Not only is ciliary structure well conserved across cell types within humans, but the same basic organization and assembly principles are conserved across the tree of life. This allows us the ability to study ciliary formation, maintenance and signaling using the unicellular green alga, Chlamydomonas reinhardtii. Many of the important breakthroughs in the history of ciliary biology were uncovered using the powerful genetic and biochemical analyses that are possible in these algae.
We and others have previously identified many different proteins/pathways that regulate cilium structure. Among them are G protein coupled receptors (GPCRs), mitogen-activated protein kinases and the actin cytoskeleton. We are currently studying mechanisms by which GPCR and mitogenic pathways coordinate with cilum formation as well as how actin dynamics regulate cilum-bound traffic. Using both Chlamydomonas and mammalian cells, our work will continue to identify fundamental principles of ciliary regulation and thereby uncover novel points of therapeutic intervention for diseases associated with ciliary dysfunction.
Avasthi P, Onishi M, Karpiak J, Yamamoto R, Mackinder L, Jonikas MC, Sale WS, Shoichet B, Pringle JR, Marshall WF. Actin is required for IFT regulation in Chlamydomonas reinhardtii. Curr Biol. 2014 Sep 8;24(17):2025-32.
Ying G, Avasthi P, Irwin M, Gerstner CD, Frederick JM, Lucero MT, Baehr W. Centrin 2 is required for mouse olfactory ciliary trafficking and development of ependymal cilia planar polarity. J Neurosci. 2014; 34(18):6377-88.
Avasthi P*, Scheel JF*, Ying G, Frederick JM, Baehr W, Wolfrum U. Germline deletion of Cetn1 causes infertility in male mice. J Cell Sci. 2013; 126(Pt 14):3204-13. *co-first authors
Avasthi P, Marley A, Lin H, Gregori-Puigjane E, Shoichet BK, von Zastrow M, Marshall WF. A chemical screen identifies class a g-protein coupled receptors as regulators of cilia. ACS Chem Biol. 2012; 7(5):911-9.
Avasthi P, Watt CB, Williams DS, Le YZ, Li S, Chen CK, Marc RE, Frederick JM, Baehr W. Trafficking of membrane proteins to cone but not rod outer segments is dependent on heterotrimeric kinesin-II. J Neurosci. 2009; 29(45):14287-98.
Guo H, Hong S, Jin XL, Chen RS, Avasthi PP, Tu YT, Ivanco TL, Li Y. Specificity and efficiency of Cre-mediated recombination in Emx1-Cre knock-in mice. Biochem Biophys Res Commun. 2000; 273(2):661-5.
Jin XL, Guo H, Mao C, Atkins N, Wang H, Avasthi PP, Tu YT, Li Y. Emx1-specific expression of foreign genes using "knock-in" approach. Biochem Biophys Res Commun. 2000; 270(3):978-82.
Guo H, Mao C, Jin XL, Wang H, Tu YT, Avasthi PP, Li Y. Cre-mediated cerebellum- and hippocampus-restricted gene mutation in mouse brain. Biochem Biophys Res Commun. 2000; 269(1):149-54.
Prachee Avasthi, Ph.D.