Abstract

The hypotheses of this proposal are focused on the molecular and cellular level deficits in genetic models of PKD. The epithelia of the renal tubule are thought to be the primary pathological entity in the development of renal cysts. While there are limitations to the study of the cell outside of its tissue context, cellular measurements provide access to a number of sophisticated techniques to measure molecular function in living cells at high spatial and temporal resolution and can thus provide molecular evidence that ultimately can be verified within in vivo models. To build cellular level models of disease we require a wide variety of measurement modalities to relate specific genetic defects to a specific cellular phenotype. Many of the techniques used in this proposal can provide key molecular evidence for deficits in specific cellular pathways. The Imaging Core facility provides a unique and complementary set of microscopy-based modalities that can make high-resolution measurements of molecular function in living cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center (P50)
Project #
5P50DK074030-05
Application #
7914147
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
5
Fiscal Year
2009
Total Cost
$86,238
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Wu, Yong; Xu, Jen X; El-Jouni, Wassim et al. (2016) G?12 is required for renal cystogenesis induced by Pkd1 inactivation. J Cell Sci 129:3675-3684
Yao, Gang; Luo, Chong; Harvey, Michael et al. (2016) Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability. Hum Mol Genet 25:448-58
Czarnecki, Peter G; Gabriel, George C; Manning, Danielle K et al. (2015) ANKS6 is the critical activator of NEK8 kinase in embryonic situs determination and organ patterning. Nat Commun 6:6023
Follit, John A; San Agustin, Jovenal T; Jonassen, Julie A et al. (2014) Arf4 is required for Mammalian development but dispensable for ciliary assembly. PLoS Genet 10:e1004170
Yao, Gang; Su, Xuefeng; Nguyen, Vy et al. (2014) Polycystin-1 regulates actin cytoskeleton organization and directional cell migration through a novel PC1-Pacsin 2-N-Wasp complex. Hum Mol Genet 23:2769-79
Wang, Shixuan; Wu, Maoqing; Yao, Gang et al. (2014) The cytoplasmic tail of FPC antagonizes the full-length protein in the regulation of mTOR pathway. PLoS One 9:e95630
Manning, Danielle K; Sergeev, Mikhail; van Heesbeen, Roy G et al. (2013) Loss of the ciliary kinase Nek8 causes left-right asymmetry defects. J Am Soc Nephrol 24:100-12
Yao, Gang; Luyten, Annouck; Takakura, Ayumi et al. (2013) The cytoplasmic protein Pacsin 2 in kidney development and injury repair. Kidney Int 83:426-37
Czarnecki, Peter G; Shah, Jagesh V (2012) The ciliary transition zone: from morphology and molecules to medicine. Trends Cell Biol 22:201-10
Jonassen, Julie A; SanAgustin, Jovenal; Baker, Stephen P et al. (2012) Disruption of IFT complex A causes cystic kidneys without mitotic spindle misorientation. J Am Soc Nephrol 23:641-51

Showing the most recent 10 out of 34 publications