Type 2 diabetes (T2D) is a long-term metabolic disorder affecting 12% of the US population. It is a leading
cause of death nationwide, primarily due to associated cardiovascular disease (CVD, >65% of patients).
While CVD risk factors include high cholesterol, hypertension, and smoking, a subset of patients suffer from
myocardial dysfunction, a term named type 2 diabetic cardiomyopathy (T2DCM), which suggest factors
within the cardiac myocyte itself may give rise to detrimental cardiac remodeling associated with diabetes.
Despite the obvious importance of T2DCM, there is currently no specific effective treatment for it and a
deep understanding of this complex disease at the molecular level is lacking. Hence, resolving the
contributing mechanisms of T2DCM is a pressing goal of basic and translational research. The recent
advent of new technological breakthroughs, such as patient-specific human induced pluripotent stem cells
(iPSCs) and genome editing, provides an unprecedented opportunity to study associations between genetic
variability and disease susceptibility. The overarching goal of our multi-PI R01 grant is to understand the
underlying mechanisms of T2DCM using patient-specific iPSC-derived cardiomyocytes and endothelial cells
from T2D patients and to understand individual susceptibility to disease development. We have assembled
a team of highly accomplished clinicians and researchers in cardiac stem cell biology, genomics, molecular
genetics, biostatistics and bioinformatics. We are well positioned to achieve the project goals within five
years. Our proposal will enable a novel personalized approach to better understand the mechanisms
underlying T2DCM that could ultimately revolutionize treatment strategies.