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Human DNA Methylation Signatures to Define Diabetic Cardiac Subtypes
Summary Data Summary
Applicant Wende, Adam
E-Mail Address arwende@UAB.edu
Project Title Human DNA Methylation Signatures to Define Diabetic Cardiac Subtypes
CBU ID 14GHSU1408
External SubContract ID 25732-52
Diabetic Complication Cardiomyopathy
Funding Program Group Pilot & Feasibility [PF2014]
Abstract Cardiovascular diseases remain the major cause of death in patients with
diabetes. Determining the role of diabetes in the progression of heart disease
is critical to the development of personalized medicine. Heart failure is
accompanied by a reprogramming of gene expression, a process that is not
completely understood. Recently, epigenetics or the contribution of non-coding
RNAs, post-translational modifications of histone proteins, and/or methylation
of DNA has emerged as a component of transcriptional regulation. Each of these
pathways directly impacts gene regulation in development, cancer, mental
illness, heart failure, and diabetes. Defining the contribution of each mode of
regulation is a hurdle to developing effective interventions. Studies in both
animal models and humans have now shown that DNA methylation is regulated both
transgenerationally and acutely. Specifically, parental diet can modify DNA
methylation patterns of offspring. This process can be reproduced acutely in
cell culture by treating cells with high glucose. The contribution of glucose
fluctuations in patients with either Type 1 or Type 2 diabetes mellitus has been
linked to the development of diabetic complications. This process is termed
鈥渕etabolic memory鈥 and is associated with epigenetic changes. Despite the
growing wealth of knowledge on epigenetics, diabetes, and the subsequent
physiological changes, relatively little is known about their role on myocardial
tissue. The hypothesis to be tested in the current study is that cardiac DNA
methylation distinguishes unique pathways in the development of heart failure. A
critical barrier to defining tissue specific molecular pathways in the
regulation of gene expression is access to human heart samples. This study will
interrogate changes in DNA modifications in the combination of diabetic,
non-diabetic, heart failure, and non-heart failure human cardiac tissue. The aim
of this study is to define DNA methylation signatures that will distinguish
diabetic cardiomyopathy and heart failure. The year of pilot and feasibility
funding will provide the means to identify potential genetic changes that will
then be tested for direct functional impact on gene expression in future R01
grant applications.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 20271
Supply Total Costs 8956
Equipment Total Costs 0
Travel/Other Total Costs 38800
Direct Costs 68027
Indirect Costs Proposed 31973
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 10/1/2014
End Date 9/30/2015
IFO Name Snider, Debra
IFO E-Mail Address deb@uab.edu
IACUC/IRB No. 999999
IACUC/IRB Institution University of Alabama at Birmingham
Entity ID No. 1636005396A6
Report Request Date 10/30/2015
T1D NO
TypeCount
Invoices 9
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  14GHSU140825732-52University of Alabama at Birmingham9/30/2015$47,617.50-$47,617.50$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham8/31/2015$20,756.81-$20,756.81$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham7/31/2015$5,385.72-$5,385.72$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham6/30/2015$6,904.56-$6,904.56$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham5/31/2015$2,770.91-$2,770.91$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham4/30/2015$1,768.20-$1,768.20$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham3/31/2015$2,533.25-$2,533.25$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham2/28/2015$7,071.38-$7,071.38$54.17View PDF
  View  14GHSU140825732-52University of Alabama at Birmingham12/29/2015$5,137.50-$5,137.50$54.17View PDF


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