Curiosity is the driving force of science
Personally, I’ve always been fascinated by the incredible machine that is the human body. This led me to pursue a career in medical research. As a fitness coach, I saw firsthand how lifestyle impacts metabolism and health. This drove me to delve deeper and truly understand complex diseases like diabetes. Diabetes has become a global health crisis affecting millions worldwide. It is a spectrum of diseases, but they all share a common feature: dysfunction of the body’s insulin producers - the pancreatic islets.
Medical research allows us to continuously learn and discover – from the organismal to the molecular level.
During my PhD in Marc Donath’s lab at the University of Basel, Switzerland, I investigated the complex interplay between inflammation and the function of insulin-producing beta cells. My research focused on the role of key inflammatory mediators (interleukins) in regulating insulin secretion. We showed that after every meal, there is a transient inflammatory response that surprisingly promotes insulin secretion and lowers blood sugar. Chronic activation of this inflammatory response, as can occur in obesity, puts a strain on beta cells, impairs them, and leads to diabetes. Another interesting finding from this research showed that not all beta cells are affected by inflammatory processes. In other words, there is heterogeneity among beta cells.
To investigate this heterogeneity, I joined Andrew Pospisilik’s group at the Max Planck Institute in Germany. My research focused on studying epigenetics in beta cells. Epigenetics explains changes in gene expression without changes (mutations) in the genes themselves, and it turned out that beta cells have epigenetic heterogeneity!
Our research results led to new insights into the role of specific epigenetic modifications to chromatin (a complex of DNA and histone proteins) in regulating gene expression, cellular identity, and function. In simpler terms, we have identified the molecular basis for the heterogeneity of beta cells.
To date, I have gained knowledge and tools from various research fields, but also many new questions about the interplay between epigenetics, inflammation, and the function of pancreatic islet beta cells. In my research group at the Hebrew University of Jerusalem, we aim to clarify how these factors contribute to the development of diabetes and, more importantly, whether we can control them? The ultimate goal: to translate our findings into novel therapeutic strategies.
Figure legend: (A) Representative 3D image of an islet. β cells and immune cells are highlighted in magenta or yellow, respectively. (B) Zoom into a region of an islet highlight interactions of cells. Scale bar 30um. (C) Live cell imaging of three adjacent nuclei of H3K27me3 reporter β cells (in white), DNA was counterstained with Hoechst (blue). The orange box highlights a magnified area within one of the nuclei. (D) Analysis of mouse islet scRNAseq data; UMAP visualisation of islet cell clusters, colours represent cell (sub)types (E) Illustration of insulin secretion assay as an example for a functional assay.
