2200 København N.
Type 1 diabetes (T1D) is a multifactorial metabolic disease caused by immune-mediated destruction of the insulin-producing ß-cells in the pancreatic islets of Langerhans. The overall goal of my research is to advance our understanding of fundamental islet biology and the detrimental mechanisms causing ß-cell failure in T1D. A better understanding of the genetic risk factors, the triggering mechanisms, the islet-immune dialogue, and the pathways leading to ß-cell death may pave the way for future therapeutic options to prevent ß-cell destruction in T1D.
Primary fields of research
We perform hypothesis-driven, multifaceted and cross-disciplinary translational research. In our work, we utilize clinical samples, ß-cell models, human islets, and mouse models. We have three overall focus areas within the T1D pathophysiology field:
Functional genomics: Based on the strong genetic component of T1D with more than 50 known risk loci, a prime target is to identify causal disease genes and to functionally validate these in ß-cells. Our hypothesis is that many risk-conferring genes operate in the ß-cells and are involved in crucial functions such as regulation of apoptotic cell death and the dialogue with the immune system. We apply various integrative systems biology approaches to pinpoint possible candidate genes that we then take further in wet lab experiments.
Inflammatory cytokines: Specific pro-inflammatory cytokines exert cytotoxic effects on ß-cells and play a crucial role in T1D. Hence, another focus area is to decipher pro-apoptotic cytokine signal transduction in islets and ß-cells. Further, the levels of pro- and anti-inflammatory cytokines in the circulation may reflect the detrimental processes going on in the pancreas during development and remission of T1D. Therefore, these factors may constitute biomarkers that can be used prognostically to predict disease course, remission potential, and risk of development of complications.
Incretin islet biology: A more recent arm of our research deals with incretin hormone biology. The incretins GLP-1 and GIP increase insulin secretion in a glucose-dependent manner and exert anti-apoptotic and proliferative effects on ß-cells. Recent research also suggests that GIP under some circumstances can stimulate α-cell glucagon secretion. However, the underlying mechanisms responsible for the effects of incretins in islets remain unclear and need further exploration. Our work is devoted to a better understanding of incretin islet biology and to explore the potential of incretins to rescue ß-cells from immune-mediated destruction. Potentially, incretin therapy constitutes a new option to increase and sustain ß-cell function in newly diagnosed T1D patients which is the long-term aim of this research.