Our group is committed to study the molecular and cellular mechanisms underlying type 1 diabetes (T1D) with particular focus on the pancreatic islet. The disease may develop over several years. Long before the onset of elevated blood glucose levels and the clinical diagnosis, which first occur when the vast majority of the beta cell mass is gone, there is evidence of early immune activation coupled with progressive changes in beta cell function. Efforts focused on more precisely identifying this silent phase of diabetes are critical to instigate preventive therapies at the earliest possible time, with the expectation of maximally preserving beta cell survival and insulin secretion. During the development of diabetes, pre-diabetes, and in response to the immune system activation, peptides, proteins, nucleic acids, and small vesicles may be released from the beta cells. We hypothesize that careful identification of the beta cell-derived components may allow for improved identification of this silent phase of diabetes.
The complexity of type 1 diabetes
The predisposition to T1D is determined by a combination of genetic and environmental factors and characterized by remarkable heterogeneity. More than 50 risk loci have been established, but the exact causal mechanisms underlying most of these await clarification. Our working hypothesis is that many of the risk-conferring genes converge at the islet level to escalate beta cell fragility towards certain inflammatory and environmental components. We put significant efforts into investigating which genes in T1D risk loci that promote disease via these mechanisms.
The complexity of T1D suggests that single biomarker approaches to T1D risk stratification will have limited application. Rather, a composite biomarker signature will be needed. We work to catalog global changes in pancreatic beta cell protein, metabolites, mRNA, non-coding RNA, and DNA signatures across a number of clinical, pre-clinical, and
in vitro platforms. The overall mission is to enhance current understanding of T1D pathophysiology and support novel strategies for earlier detection, prevention, and treatment of T1D.