The diagnosis of Type 1 diabetes (T1D) is currently limited by methods that detect the disease at relatively late stages, when blood glucose levels rise and autoimmune attack is well underway. By this stage, given the treatments presently available (insulin injection), the b cell loss is de facto, irreversible. Biomarkers for early detetion of ? cell stress, before this late stage, would improve diagnosis and open up new windows to monitor and possibly treat the disease. We will produce functionally mature, "never-before-stressed", ? cells from human pluripotent stem cells and use these cells to identify biomarkers for the earliest stages of ? cell stress by providing various stress conditions ex vivo. In additin, we can use stem cells from T1D and control patients to investigate differences in their ? ell responses to stress. In other words, we can ask: are ? cells in T1D patients especially sensitive to stress or in other ways defective before an immune attack? Successful identification of early ? ell-specific biomarkers for stress will enable earlier detection and diagnosis, better tracking f progress from asymptomatic to clinical presentation, and a more mechanistic understanding of the earliest stages and possibly initiating events of human T1D.

Public Health Relevance

Diagnosis and treatment of Type 1 Diabetes is dependent upon clinical presentation and detection of autoantibodies within the patient's blood. This method of detection is costly, time consuming, and is not informative regarding the remaining functional beta cell mass, and because it is an immune-based or indirect test, it cannot accurately measure the disease state with respect to insulin production. We propose to identify novel secreted biomarkers that quantitatively indicate early beta cell stress. These markers will denote beta cell stress before autoimmune destruction and may therefore allow for an early and more accurate prediction, monitoring, and treatment during the onset and progression of T1D.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
High Impact Research and Research Infrastructure Cooperative Agreement Programs—Multi-Yr Funding (UC4)
Project #
1UC4DK104159-01
Application #
8813227
Study Section
Special Emphasis Panel (ZDK1-GRB-S (O4))
Program Officer
Sato, Sheryl M
Project Start
2014-09-23
Project End
2017-08-31
Budget Start
2014-09-23
Budget End
2017-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$1,593,083
Indirect Cost
$618,142
Name
Harvard University
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138