Helman Lab

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.

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.

Research

Metabolism and Function of Beta Cells

Nutritional Transitions in Development and Aging

Maturation of Stem-Cell Derived Beta Cells

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.

Cellular Adpt

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.

Stem Cells

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.

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.

Cellular Maladaptation

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.

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.

Publications

Nutrient Sensing

Cellular Senescence

A Nutrient-Sensing Transition at Birth
Triggers Glucose-Responsive Insulin Secretion, (2020), Cell Metabolism

p16(Ink4a)-Induced Senescence of Pancreatic

Beta Cells Enhances Insulin Secretion, (2016), Nature Medicine

Full list of publications

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.

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.