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Epigenetic changes and methylglyoxal adducts in patients with type 1 diabetes that develop diabetic kidney disease
Summary Data Summary
Applicant Shuck, Sarah
E-Mail Address sshuck@coh.org
Project Title Epigenetic changes and methylglyoxal adducts in patients with type 1 diabetes
that develop diabetic kidney disease
CBU ID 20AU4128
External SubContract ID 30835-71
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2020]
Abstract The incidence of type 1 diabetes (T1D) has increased as much as 3-4% annually in
recent decades. Patients with T1D are vulnerable to developing diabetic kidney
disease (DKD), a leading cause of death in this population. DKD is not diagnosed
until kidney function is irreversibly lost, limiting clinical interventions. To
reduce DKD-associated mortality in patients with T1D, there is a critical need
to identify susceptible populations prior to DKD onset so that preventative
therapies can be implemented. To do this, we must identify the specific cellular
factors involved in disease etiology. A promising source of these mediatory
cellular factors is poor glycemic control, which is significantly associated
with DKD. To identify and characterize these factors, we, along with our
collaborator Dr. Rama Natarajan, have accessed samples from an established,
longitudinal clinical study investigating the role of glycemic control on
complication progression. Analysis of samples collected pre-DKD development
revealed specific metabolites and epigenetic signatures associated with poor
glycemic control; we hypothesize that these may have utility as predictive
biomarkers of DKD and will explore this in Aim 1. Analysis of samples collected
post-complication development revealed that these same metabolic and epigenetic
markers remained elevated over time, even after strong glycemic control was
established. We hypothesize that these markers are indicative of long-term poor
glycemic control and will explore this in Aim 2. Our goals for Aims 1 and 2 are
to build a predictive model for DKD and determine the extent to which metabolic
and epigenetic markers are associated with poor glycemic control. Beyond the
utility of metabolic and epigenetic markers for predicting and monitoring
disease progression, we discovered that they influence specific cellular
pathways such as glycolysis, lipolysis, proteolysis, and inflammation. We
hypothesize that interrelated components of these pathways play a role in
complication etiology and will explore this in Aim 3. Our goal in Aim 3 is to
establish the foundational information to explore the role of specific pathway
components in complication etiology and progression. The work in this proposal
is the first example of combined analysis of metabolic and epigenetic markers in
DKD etiology.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Rama Natarajan
John Kaddis
Ching Ouyang
Tala Zoukari
Salary Total Costs 37584
Supply Total Costs 5000
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 42584
Indirect Costs Proposed 32364
Total Costs Proposed 74948
Total Costs Approved 74948
Start Date 11/1/2020
End Date 10/31/2021
IFO Name Steres, Yong
IFO E-Mail Address ysteres@coh.org
IACUC/IRB No. 18071
IACUC/IRB Institution Beckman Research Institute of City of Hope
Entity ID No. 95-3432210
Report Request Date 10/31/2021
T1D NO
TypeCount
Invoices 6
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  20AU412830835-71Beckman Research Institute of City of Hope7/15/2021$14,959.97$11,369.58$26,329.55-View PDF
  View  20AU412830835-71Beckman Research Institute of City of Hope6/10/2021$5,369.70$4,080.97$9,450.67-View PDF
  View  20AU412830835-71Beckman Research Institute of City of Hope5/10/2021$2,457.69$1,867.84$4,325.53-View PDF
  View  20AU412830835-71Beckman Research Institute of City of Hope4/8/2021$624.37$474.53$1,098.90-View PDF
  View  20AU412830835-71Beckman Research Institute of City of Hope3/10/2021$666.04$506.20$1,172.24-View PDF
  View  20AU412830835-71Beckman Research Institute of City of Hope12/16/2021$18,506.23$14,064.88$32,571.11-View PDF


Reports
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