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Identification of regulatory gene networks in the morphologic progression of diabetic nephropathy
Summary Data Summary
Applicant Hodgin, Jeffrey
E-Mail Address jhodgin@umich.edu
Project Title Identification of regulatory gene networks in the morphologic progression of
diabetic nephropathy
CBU ID 12GHSU200
External SubContract ID 25034-16
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2012]
Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the
United States and has a significant impact on human suffering. Mouse models of
DN have elucidated important mechanisms contributing to disease progression;
however, candidate pathway approaches have yielded limited results. We propose
to employ a systems approach to define underlying molecular processes associated
with structural damage in DN. The objective of this project is to identify
genes and elucidate transcriptional networks that play a role in the development
of progressive renal pathology of obesity-induced type 2 diabetes in mice, and
then perform cross-species comparison to human transcriptional networks and
morphometric analysis of DN. In this proposal, we will employ a rich dataset
derived from the intercross of mouse strains resistant (C57BL/6 or B6) or
susceptible (BTBR) to diabetes induced by the leptinob mutation. The resulting
F2 population (> 500 mice) has been surveyed for many clinical traits and
reflects a wide range of susceptibility to diabetic nephropathy. All mice were
genotyped for 5,000 single nucleotide polymorphisms (SNPs), 2,000 of which were
polymorphic between B6 and BTBR. In addition, gene expression of whole kidney
has been surveyed in all F2 mice. We will conduct detailed morphologic
examination of formalin-fixed, paraffin-embedded kidneys from all F2 mice,
capturing pathologic features as outlined by the DCC such as glomerular
mesangial expansion and tubulointerstitial fibrosis. The resulting gene
regulatory networks and correlations to clinical and morphologic features will
then be compared to renal transcriptional profiling and detailed morphometric
analyses previously obtained from a cohort of Southwestern American Indians
(n=40) with type 2 diabetes in which protocol kidney biopsies were performed.
Our study will yield an unprecedented dataset that will allow us to develop
causal regulatory networks that reveal the interaction among genes and
intermediate gene expression to the pathophysiology of DN relevant to human
disease. Aim 1: Define causal gene regulatory networks of progressive pathologic
features of murine DN with a detailed survey of renal morphology in mice that
have been genotyped and whole kidney gene expression profiling has been
performed. Aim 2: Compare the morphology-derived gene networks obtained from Aim
1 to human kidney transcriptional profiling and morphometric analysis to
identify networks relevant to human disease.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 30376
Supply Total Costs 3000
Equipment Total Costs 0
Travel/Other Total Costs 5209
Direct Costs 38585
Indirect Costs Proposed 21415
Total Costs Proposed 60000
Total Costs Approved 60000
Start Date 10/1/2012
End Date 9/30/2013
IFO Name Madden, Thomas E.
IFO E-Mail Address thommad@umich.edu
IACUC/IRB No. PRO00003293
IACUC/IRB Institution University of Michigan-Ann Arbor
Entity ID No. 38-6006309
Report Request Date 1/1/3000
T1D NO
TypeCount
Invoices 10
Progress Reports 0
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor9/6/2013$9,565.82$5,309.03$14,874.85-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor8/6/2013$7,267.38$4,033.40$11,300.78-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor7/5/2013$2,936.64$1,581.26$4,517.90-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor6/6/2013$2,819.48$1,564.81$4,384.29-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor5/6/2013$2,739.82$1,520.60$4,260.42-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor4/4/2013$2,831.54$1,571.51$4,403.05-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor3/6/2013$3,967.29-$3,967.29-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor2/6/2013$2,598.63$1,442.24$4,040.87-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor10/4/2013$1,017.33-$1,017.33-View PDF
  View  12GHSU20025034-16University of Michigan-Ann Arbor1/7/2013$4,651.59$2,581.63$7,233.22-View PDF
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