RESEARCH
The Beta Cell Aging Lab aims to understand the aging process, and senescence in particular, of insulin-secreting beta cells and how this process contributes to the development of Type 1 and Type 2 diabetes. This knowledge will lead to the identification of new pharmacological and non-pharmacological interventions that can be translated into the clinic and alter the course of the disease.
OUR RESEARCH LINES
AT A GLANCE
RESEARCH LINES
Molecular progression to senescence
Researcher:
Francesko Hela
Cellular senescence is one of the main mechanisms of beta-cell aging. This project will identify the different stages a beta-cell goes through as it becomes senescent, which of these stages are reversible and which are not, and how they can be targeted.
Determine the β-cell SASP
Researcher:
Stephanie Sanjines
Senescent beta-cells secrete a unique SASP that impairs the function and proliferative capacity of neighboring non-senescent beta cells. We will generate a robust discovery platform to identify new members of the beta-cell SASP and understand their role on the function and proliferative capacity of neighboring cells.
Effective
senotherapeutics
Researcher:
Cristian Abarca
We have shown that deleting senescent beta cells (senolysis) improves their function and restores their identity. We want to identify effective beta-cell senolytic drugs and interventions, such as exercise, as a way to counteract the effect of accelerated cellular aging during the progression of diabetes.
Effects of stressors on β-cell senescence and autophagy
Researcher:
Francesko Hela
Senescence is a stress response to various insults such as telomere attrition, UV light, oncogene activation, oxidative stress, mitochondrial dysfunction and DNA damage. Additionally, senescence is a heterogeneous state that can accumulate different markers even in the same cell type. This project will evaluate the effects of different stressors on b-cell senescence and how that relates to autophagy, a cellular event that decreases with age.
Effects of exercise on β-cell senescence
Researcher:
Priscila Carapeto
Increased β-cell senescence contributes to the development of type 2 diabetes (T2D). Exercise is critical in the treatment of T2D and can attenuate aging-associated cellular changes, but exercise effects on β-cell senescence are unknown. This project tests the effects of aerobic exercise on b-cell senescence using mouse models and samples from humans with T2D to elucidate novel pathways to recover cell function and identity.
Mechanisms of accelerated biological age in Type 2 Diabetes
Researcher:
Briana Cortez
Islet transplantation (Tx) is an effective intervention to prevent severe hypoglycemia and provide insulin independence in type 1 diabetes (T1D). Previous studies have shown that islets from older donors are less effective in reversing blood glucose (BG) than those of younger ones. Cellular senescence leads to age-related β-cell dysfunction and drives alloimmune responses to organs from older donors, but can be targeted through senolysis. However, the mechanism of pancreatic β-cell senescence in transplant grafts and its pathological significance remain to be elucidated. This project aims to understand the potential role that cellular senescence plays in loss of graft functionality/viability and whether the use of senolysis may ameliorate it.
Role of β-cell senescence in graft function and survival in islet transplantation
Researcher:
Kanako Iwasaki
Islet transplantation (Tx) is an effective intervention to prevent severe hypoglycemia and provide insulin independence in type 1 diabetes (T1D). Previous studies have shown that islets from older donors are less effective in reversing blood glucose (BG) than those of younger ones. Cellular senescence leads to age-related β-cell dysfunction and drives alloimmune responses to organs from older donors, but can be targeted through senolysis. However, the mechanism of pancreatic β-cell senescence in transplant grafts and its pathological significance remain to be elucidated. This project aims to understand the potential role that cellular senescence plays in loss of graft functionality/viability and whether the use of senolysis may ameliorate it.
