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Jeremy Reiter, M.D., Ph.D. - Assistant Professor
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Kevin Corbit, Ph.D. - Postdoctoral Fellow
I am interested in the role primary cilia play during mammalian development. Specifically, I am investigating the requirement of cilia for proper transduction of Hedgehog signals. In addition, I have engineered mouse lines that lack primary cilia specifically in the endothelium in order to ascertain the role these organelles have in vascular development as well as tumor angiogenesis.
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Bill Dowdle - Graduate Student, Tetrad Program
I am interested in how primary ciliogenesis occurs in differentiated somatic cells of adult organisms. The regulation of centrosome duplication is intimately linked will the cell cycle and has been heavily studied, but precise mechanisms regulating ciliogenesis during the G1 phase of the cell cycle and cilia dissasembly prior to S phase remain elusive. Understanding why ciliogenesis is limited to the older centriole in the centrosome pair and how maturation of the older centrosome is regulated is also sure to provide insight into this incredible cellular process.
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Francesc Garcia-Gonzalo, Ph.D. - Postdoctoral Fellow
Tectonic (from the Greek tekton, meaning “builder”) is a secreted glycoprotein that regulates sonic hedgehog (Shh) signaling in the developing mouse embryo. Despite extensive analyses of the phenotypes exhibited by embryos lacking Tectonic, the molecular mechanisms underlying Tectonic actions are still largely mysterious. Since primary cilia are known to be required for mammalian Shh signaling, an interesting possibility is that Tectonic exerts its effects on the Shh pathway by controlling primary cilia formation. My goal is to test this hypothesis and to shed more light on the molecular events in which Tectonic partakes.
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Julie Gaulden - Graduate Student, BMS Program
I’m a Biomedical Sciences graduate student and joined the Reiter lab at the beginning of 2007. I am currently working on two projects, both of them centered on mouse embryonic stem cells (mESC). Primary cilia are essential for normal vertebrate development, but it is unknown at what developmental stage cilia are first required. Using mESC, I am examining the role of cilia in mESC differentiation to help elucidate ciliary functions in early development. In the second project, I am investigating the function of several pluripotency genes and how the interactions of these candidate proteins change during differentiation.
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Nicole Santos - Graduate Student, Biomedical Sciences Program
Despite its central role in the Hedgehog pathway, the mechanisms by which Smoothened (Smo) activates its downstream pathway remain poorly understood. Although Smo displays homology to G-protein coupled receptors and is most similar to Frizzled 7TM proteins, Smo is not thought to function through G-proteins, nor is it known to bind a ligand. However, several studies have proposed critical events necessary to activate Smo, such as changes in conformation, phosphorylation and subcellular localization. Work from our lab demonstrated that vertebrate Smoothened functions at the primary cilium. Smo moves to the cilium in response to Hh, and disruption of this transport blocks Hh pathway activation. I am interested in a cell biological understanding of how Smo localization to the cilium is determined and why this movement is critical for downstream pathway activation.
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Amy Shyer - Research Technician
I am interested in the relationship between primary cilia and important developmental pathways, such as Hedgehog and Wnt. I am conducting a microarray utilizing several cell types to further investigate the function of primary cilia. I am also investigating a phenotype seen in mice with a mutation in a novel ciliagenesis gene.
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Veena Singla - Graduate Student, Tetrad Program
Orofaciodigital syndrome type 1 (OFD1) is a human congenital syndrome characterized by malformations of the face, oral cavity, and digits, as well as polycystic kidney disease. Polycystic kidney disease can be caused by defects in primary cilia function, suggesting that OFD1 may be due to ciliary dysfunction as well. Additionally, the product of the gene responsible for OFD1 localizes to basal bodies at the origin of primary cilia. To test the hypothesis that OFD1 is required for ciliary function, we generated a murine embryonci stem cell line with a loss-of-function in the OFD1 gene. OFD1-deficient cells completely and specifically lack primary cilia. The lack of cilia is due to the loss of OFD1, as revealed by the restoration of ciliogenesis upon reversion of the OFD1 mutation. Immunoflourescence analysis of OFD1-deficient cells demonstrates that OFD1 is required for normal centrosomal assembly. Together these data suggest that OFD1 is an essential component of the centrosome, and that in the absence of OFD1, the centrosome cannot support ciliogenesis. We ae currently using live cell imaging, proliferation analysis, and transmission electron microscopy to understand how OFD1 controls cilia formation and other aspects of centrosomal function.
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Sunny Wong, Ph.D. - Postdoctoral Fellow
Cilia are important for Hedgehog signaling, a pathway which is frequently upregulated in cancer. I am therefore examining whether cilia are important for tumorigenesis using transformed cell lines and in vivo mouse models.
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Victoria Wu, Ph.D. - Postdoctoral Fellow
G-Protein coupled receptors (GPCR) are 7-transmembrane spanning receptors that can mediate a broad spectrum of extracellular signals which then mediate cell signaling in a variety of biological processes. One such GPCR is GPR107, a novel GPCR that is required for early development of the mouse embryo. GPR107 appears to be an ancient GPCR that is conserved from humans to mouse, down to the signal celled green algae chlamydomonas. GPR107 localizes to the primary cilium and its absence results in developmental defects as early as E7.5. GPR107 is the only GPCR known to be involved in early development and I am working to further elucidate its role and function in early embryogenesis.
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