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MicroRNA Regulation in the Type 2 Diabetic Human Heart
Summary Data Summary
Applicant Hollander, John
E-Mail Address jhollander@hsc.wvu.edu
Project Title MicroRNA Regulation in the Type 2 Diabetic Human Heart
CBU ID 13GHSU289
External SubContract ID 25034-38
Diabetic Complication
Funding Program Group Pilot & Feasibility [PF2013]
Abstract Diabetic cardiomyopathy is an impairment of heart muscle, characterized by
metabolic disturbance and contractile dysfunction. The mitochondrion is central
in the development of diabetic cardiomyopathy however, examination of
mitochondria is complicated by the fact that two subpopulations are present in
the cardiac myocyte, interfibrillar mitochondria (IFM) which situate between the
contractile apparatus, and subsarcolemmal mitochondria (SSM), which exist
beneath the plasma membrane. Research from our laboratory using a mouse model of
type 2 diabetes mellitus (db/db) have revealed a robust dysfunctional profile
particularly to cardiac SSM, as indicated by disruption of energetics and
proteomic make-up. MicroRNAs (miRNA) are non-coding RNAs that have been shown to
regulate protein expression of target mRNAs. Data from our laboratory indicates
that miRNA profiles in the heart are dynamic following diabetic insult. Further,
our results indicate that the mitochondrion possesses a pool of miRNAs that
translocate into and out of the organelle in a dynamic fashion. Currently, it is
unclear whether similar phenomena exist in type 2 diabetic human heart or
whether miRNAs outside or within the mitochondrion are associated. The
objectives of this application are: (1) to assess the impact of type 2 diabetes
mellitus on cardiac transcriptome profiles in atrial appendage tissue from
diagnosed type 2 diabetic patients and non-diabetic patients; and (2) to assess
the impact of type 2 diabetes mellitus on cardiac mitochondrial subpopulation
proteomes in atrial appendage tissue from diagnosed type 2 diabetic patients and
non-diabetic patients. With respect to expected outcomes, the combination of
work proposed in our discovery-based experiments will provide identification of
transcriptomic and proteomic targets for therapeutic intervention in the type 2
diabetic human heart while validating the biological relevance of the db/db
mouse model. The results will enable progression in this field by establishing
the clinical applicability of mitochondrial subpopulation-based therapeutic
examinations in the diabetic heart. The data from these experiments will be
critical for our future NIH R01 grant application examining energetic
abnormalities in the type 2 diabetic heart.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 15214
Supply Total Costs 6826
Equipment Total Costs 0
Travel/Other Total Costs 18500
Direct Costs 40540
Indirect Costs Proposed 19460
Total Costs Proposed 60000
Total Costs Approved 60000
Start Date 10/1/2013
End Date 9/30/2014
IFO Name Durbin, Daniel
IFO E-Mail Address dan.durbin@mail.wvu.edu
IACUC/IRB No. 9999
IACUC/IRB Institution West Virginia University
Entity ID No. 550665758
Report Request Date 10/30/2014
T1D NO
TypeCount
Invoices 8
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  13GHSU28925034-38West Virginia University9/2/2014$4,070.68-$4,070.68$0.00View PDF
  View  13GHSU28925034-38West Virginia University8/1/2014$4,831.46-$4,831.46$0.00View PDF
  View  13GHSU28925034-38West Virginia University7/2/2014$4,416.24-$4,416.24$0.00View PDF
  View  13GHSU28925034-38West Virginia University6/2/2014$12,677.44-$12,677.44$0.00View PDF
  View  13GHSU28925034-38West Virginia University5/1/2014$2,793.90-$2,793.90$0.00View PDF
  View  13GHSU28925034-38West Virginia University4/1/2014$5,656.50-$5,656.50$0.00View PDF
  View  13GHSU28925034-38West Virginia University3/4/2014$6,778.99$3,253.91$10,032.90$0.00View PDF
  View  13GHSU28925034-38West Virginia University11/20/2014$15,520.88-$15,520.88$0.00View PDF


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