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Identifying Alterations in Mitochondrial Dynamics Associate
Summary Data Summary
Applicant Feldman, Eva
E-Mail Address efeldman@med.umich.edu
Project Title Identifying Alterations in Mitochondrial Dynamics Associate
CBU ID 16GRU3670
External SubContract ID 30835-12
Diabetic Complication Neuropathy & Neurocognition
Funding Program Group Pilot & Feasibility [PF2016]
Abstract Diabetes is a growing epidemic, affecting more than 387 million individuals
worldwide. Up to 60% of diabetic patients have diabetic neuropathy (DN), a
debilitating microvascular complication that results in the progressive loss of
sensory nerve function in the extremities. Despite the deleterious impact of DN,
therapies for the disease are limited to symptomatic relief. To develop
effective treatments that specifically target DN, a mechanistic understanding of
molecular pathways that result in neurological dysfunction associated with
diabetes is needed. Recent evidence suggests that dyslipidemia, rather than
hyperglycemia, is the clinical parameter that correlates with the progression of
DN. Since metabolic pathways converge on the mitochondria (Mt), these organelles
play a central role in maintaining neuronal cellular function and energy
homeostasis through mitochondrial (Mtl) trafficking mechanisms and endoplasmic
reticulum (ER)-mediated calcium signaling pathways. However, metabolic overload
associated with diabetes may result in aberrant calcium dynamics in the primary
sensory neurons of the nervous system, the dorsal root ganglia (DRG), resulting
in diminished Mtl trafficking and cell death induced by ER-Mt contact sites. We
hypothesize that hyperlipidemia increases the level of ER-Mt contact sites in
DRG neurons, creating a localized calcium flux which triggers Mtl apoptosis and
halts Mtl trafficking. We will test this hypothesis by 1) evaluating the role of
ER-Mt interactions in Mtl dysfunction and neuronal cell death in the DRG and
sural nerve of a high fat (HF)-fed mouse model, and 2) identifying changes in
calcium dynamics that impair Mtl trafficking in hyperlipidemic DRG neurons.
These studies will provide important insight into the role of Mtl dynamics in DN
and thereby support our long-term goal of identifying therapeutic targets that
specifically improve Mtl function and restore nerve function to patients with
DN.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 46863
Supply Total Costs 8697
Equipment Total Costs 0
Travel/Other Total Costs 8956
Direct Costs 64516
Indirect Costs Proposed 35484
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 10/1/2016
End Date 9/30/2017
IFO Name Talley, Debora
IFO E-Mail Address dtalley@umich.edu
IACUC/IRB No. PRO00006140
IACUC/IRB Institution University of Michigan
Entity ID No. 386006309
Report Request Date 10/30/2017
T1D NO
TypeCount
Invoices 10
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  16GRU367030835-12University of Michigan9/13/2017$1,333.26$2,943.18$4,276.44-View PDF
  View  16GRU367030835-12University of Michigan8/4/2017$6,184.85$3,401.67$9,586.52-View PDF
  View  16GRU367030835-12University of Michigan7/10/2017$5,134.65$614.16$5,748.81-View PDF
  View  16GRU367030835-12University of Michigan6/6/2017$16,870.50$9,278.78$26,149.28-View PDF
  View  16GRU367030835-12University of Michigan5/6/2017$5,135.22$2,824.37$7,959.59-View PDF
  View  16GRU367030835-12University of Michigan5/4/2017$17,646.69$9,705.68$27,352.37-View PDF
  View  16GRU367030835-12University of Michigan3/6/2017$5,135.23$2,824.38$7,959.61-View PDF
  View  16GRU367030835-12University of Michigan2/6/2017$5,630.62$2,336.63$7,967.25-View PDF
  View  16GRU367030835-12University of Michigan11/16/2017$1,445.09$794.83$2,239.92-View PDF
  View  16GRU367030835-12University of Michigan1/7/2017$490.46$269.75$760.21-View PDF


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