Cohorts of patients with T1D who exhibit extremes of phenotypes, such as resistance or sensitivity to long-term complications, will be analyzed for metabolic features that may explain their health. Thus, we are looking beyond HbA1c as the sole predictor of risk of reduced quality of life.
We are using this information to develop induced pluripotent organoids, models of organs that are affected by diabetes, to test for drugs that may optimize their function. This information will lead to the development of new drug treatments to improve outcomes.
Beta cell replacement therapy is a promising approach as a cure for T1 diabetes. This type of therapy has been met with minimal success due to ineffective insulin secretion. Promising in vitro data suggests that the metabolic environment of beta cells is key to cell maturation and proper insulin secretion.
This project seeks to fully understand the beta cell maturation process with modulated metabolic environment. This complete understanding provides the foundation to improved beta cell function following transplantation into patients.
Complications and disease burden among multiple organs is a hallmark of long-term T1D. Mechanism-based therapeutic targets and predictive biomarkers having been sorely lacking for T1D patients.
This project will comprehensively define the metabolic profiles across multiple T1D cohorts for association analysis with a variety of organ complications, thus providing a data-driven path toward improved T1D patient care and reduced burden.
Potential targets and biomarkers can be tested in laboratories as the latest technologies become standards in the laboratory including testing in lab derived organs (organoids) like those derived from kidney, eye and nervous system.