The epigenome maps of human diabetic kidney disease
It is believed that T1DM still shortens life expectancy by about 10 years and this is due to the long term complications of diabetes; cardiovascular and renal disease. Epidemiological studies repeatedly demonstrated that renal disease shows the strongest correlation with excess mortality. The annual mortality rate of patients who reached end stage kidney failure due to T1DM is about 20%, which is worse than many solid tumors (prostate, breast, colon cancer). Twin studies uncovered the role of genetic predisposition, however, despite the intense search over the last 11 years, no single causal gene has emerged. Clinical studies have established that intensive blood glucose and blood pressure control significantly reduces the incidence of diabetic kidney disease (DKD), but did not eliminate it. In addition, results from the Epidemiology of Diabetes Interventions and Complications (EDIC) trial have revealed that the deleterious end-organ effects continued to operate more than 15 years after the patients had returned to usual glycemic control and is interpreted as a memory or a legacy of past glycemia known as “hyperglycemic memory”. Clinical observational evidence is also strong on showing the effects of in utero environment on metabolic syndrome, hypertension and renal disease, a phenomenon called “fetal programming”. An epigenome is an intermediate phenotype that is causally "closer" to environmental and genetic factors and thus can provide very useful information for studies attempting to identify disease susceptibility factors in DKD; a prime example of a gene environmental disease. This hypothesis will be tested in the current proposal, which builds on unique tissue and cell sample collections from patients with T1D and a team of collaborative scientists, who will be able apply state-of-the-art epigenetic approaches to test this hypothesis

Single cell transciptomics of diabetic kidney disease
Diabetic kidney disease (DKD) the 9th leading cause of death in the US; one in ten Americans are affected by DKD. The yearly mortality rate of patients on dialysis can be as high as 20%, which is higher than that of patients with prostate or breast cancer. DKD is a gene environmental disease. In the US three quarters of DKD develops as a consequence of diabetes and hypertension, but a genetically susceptible host is needed for disease development. Critical cell type(s) responsible for disease development remains unknown limiting DKD understanding.

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