¿´Æ¬ÊÓƵ

Object moved to here.

¿´Æ¬ÊÓƵ :: Pilot & Feasibility Program Application

¿´Æ¬ÊÓƵ


Identifying genomic pathways associated with fibrosis in diabetic nephropathy
Summary Data Summary
Applicant Bomsztyk, Karol
E-Mail Address karolb@u.washington.edu
Project Title Identifying genomic pathways associated with fibrosis in diabetic nephropathy
CBU ID 12GHSU190
External SubContract ID 25034-23
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2012]
Abstract Diabetic nephropathy (DN) is the most common cause of end-stage renal disease in
the US. Our long term goal is to define mechanisms responsible for progression
and reversal of DN, and to establish a basis for therapeutics to reverse DN.
Fibrosis in the glomerulus and tubulointerstitium is a major contributor to the
decline of renal function in DN. Although traditionally fibrosis in DN has been
thought to be irreversible there are indications that resolution of renal
fibrotic lesions is possible. Importantly there is evidence that regression of
fibrosis is sufficient to improve renal function. Still, there are no treatments
specifically indicated to target reversal of renal fibrosis. The Alpers lab has
shown that the BTBR mouse strain with the ob/ob leptin-deficiency mutation
develops Type 2 diabetes (T2D) and severe DN. We present evidence that full
reversibility of DN can be achieved in this model with leptin replacement.
Several kinase cascades have been implicated in DN (e.g. ERKs, PKCs, Jaks).
Chromatin immunoprecipitation (ChIP) assays revealed that
kinases/phosphatases/receptors previously implicated in fibrogenesis can be
found at genes involved in fibrogenesis. Thus, our overall hypothesis is that
characterization of these signaling factors at fibrogenic genes during DN
progression and regression can identify new targets for pharmacologic inhibitors
to reverse fibrosis in DN. We have developed a high-throughput multiplex
chromatin immunoprecipitation platform, Matrix ChIP-MeDIP, and computational
tools that taken together for the first time make it possible to simultaneously
study nuclear signaling cascades immediately upstream of
chromatin/transcriptional events.
The Specific Aim of this pilot project is to demonstrate the feasibility of
defining differences in signaling enzymes/receptors at fibrogenesis-related
genes in kidneys from wild-type BTBR compared to the T2D BTBR ob/ob mice. The
proposed transforming strategy to characterize signaling pathway alterations at
fibrogenic genes specific to progression and regression of diabetes
complications is the first of its kind to identify and then test novel
therapeutic targets in the nucleus for pharmacologic inhibition to prevent and
reverse renal fibrosis in DN.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 43501
Supply Total Costs 11045
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 54546
Indirect Costs Proposed 5455
Total Costs Proposed 60001
Total Costs Approved 60000
Start Date 10/1/2012
End Date 9/30/2013
IFO Name DeFries, Kirsten
IFO E-Mail Address kirsten5@u.washington.edu
IACUC/IRB No. 2281-06
IACUC/IRB Institution University of Washington
Entity ID No. A3464-01
Report Request Date 10/30/2013
T1D NO
TypeCount
Invoices 10
Progress Reports 1
Experiments 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  12GHSU19025034-23University of Washington9/10/2013$6,646.84$664.69$7,311.53-View PDF
  View  12GHSU19025034-23University of Washington8/9/2013$7,388.92$738.89$8,127.81-View PDF
  View  12GHSU19025034-23University of Washington7/10/2013$5,561.25$556.13$6,117.38-View PDF
  View  12GHSU19025034-23University of Washington6/10/2013$5,915.76$591.57$6,507.33-View PDF
  View  12GHSU19025034-23University of Washington5/10/2013$5,394.52$539.45$5,933.97-View PDF
  View  12GHSU19025034-23University of Washington4/10/2013$5,376.47$537.65$5,914.12-View PDF
  View  12GHSU19025034-23University of Washington4/1/2014$4,550.09$455.01$5,005.10-View PDF
  View  12GHSU19025034-23University of Washington3/11/2013$1,436.14$143.62$1,579.76-View PDF
  View  12GHSU19025034-23University of Washington11/12/2013$6,075.90$607.60$6,683.50-View PDF
  View  12GHSU19025034-23University of Washington10/10/2013$6,199.56$619.94$6,819.50-View PDF


Reports


Experiments
Click here to cancel and return to funding program application

*Author:
*SubContract:
*Select File:

Click browse and select the file to upload.
(Please upload ONLY TXT, Image Files (not histolgy), PDF, XLS, XLSX, DOC, or DOCX files.)