The objective of this project is to investigate the role of the podocyte as a structural element within the glomerulus. This function may be undermined in pathologic states associated with glomerular hypertension, resulting in podocyte injury and glomerulosclerosis. Thus, defining the role of the podocyte in maintaining glomerular structure in the face of mechanically unfavorable environments will help identify new approaches to delay kidney disease progression to end stage renal failure. The first phase of this project will characterize the potential of the podocyte to maintain a basal level of intracellular tension between attachment sites at the cellular processes, using cultured human podocytes grown on a well-characterized force measurement substrate. The next phase will investigate how the force-generating properties of podocytes change when the function of certain cytoskeletal elements, particularly myosin contractile proteins, is interfered with. Candidate myosins will be identified using publicly available serial analysis of gene expression (SAGE) data, and the effect of pharmacologic agents and mRNA interference upon the presence and mechanical function of these myosins will be assessed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK072625-01
Application #
6997486
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Rankin, Tracy L
Project Start
2006-03-01
Project End
2008-02-29
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2005
Total Cost
$53,492
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Henderson, J M; Al-Waheeb, S; Weins, A et al. (2008) Mice with altered alpha-actinin-4 expression have distinct morphologic patterns of glomerular disease. Kidney Int 73:741-50