Studying Adaptive Mechanisms to Nutritional Challenges
The Hebrew University of Jerusalem
The Robert H Smith
Faculty of Agriculture, Food and Environment
How do we adapt
to nutritional changes?
Our lab studies new mechanisms in which beta cells, and other hormone-secreting cells in the pancreas, adapt to nutritional transitions. We focus on beta (insulin) and alpha (glucagon) cells, that orchestrate whole-body nutrient homeostasis during fasting and feeding. Specifically, we dissect the metabolic and functional heterogeneity of the pancreatic endocrine cells in sensing and responding to nutrients.
We are also interested to understand how maladaptation of these cells contributes to age-related diseases such as diabetes and cancer, in order to design new therapeutic strategies. In addition, we will take chemical and metabolic approaches to find key regulators of human stem cell-derived beta-cell maturation.
Investigating cellular adaptation to nutritional changes
Pancreatic beta cells are considered “nutrient sensors” as they constantly monitor nutrient levels, however it is still largely unknown how beta cells integrate environmental signals to coordinate their metabolism and function. We will study the cellular heterogeneity in nutrient sensing by beta cells. How it controls functional differences between individual beta cells, the functionality of the entire organ, and helps in maintaining metabolic homeostasis during nutritional changes.
Studying cellular maladaptation in age-related diseases
Aging is often accompanied by diet-induced obesity which is associated with an abundance of circulating nutrients, growth factors, and hormones that may lead to insulin resistance, beta cell dysfunction, and type 2 diabetes. We will investigate how beta cells adapt to metabolic stress such as insulin resistance and what is the mechanistic basis of adaptation.
Using stem cells to study human beta cell metabolism and function
Functional beta cells can be derived from human pluripotent stem cells and produce islet-like organoids (SC-islets). This unlimited source of human beta cells enables us to conduct metabolomic and chemical screens, to investigate the metabolic effects of nutritional stress on the metabolism of human pancreatic beta cells and to improve SC-beta cell maturation.
The Rehovot Campus
The Robert H. Smith Faculty of Agriculture, Food and the Environment is located in the city of Rehovot in the coastal plain. The Faculty was established in 1942 and is the only institution of higher learning in Israel that offers both teaching and research programs in these respective fields.
My lab belongs to the Department of Biochemistry,
Food and Nutrition.
Noy Bar David