Principal Investigator: Andisheh Abedini, PhD

Andisheh Abedini, PhD

Research Summary

In metabolic disease, multiple pathological factors including oxidative stress, chronic inflammation and pancreatic islet amyloidosis-induced toxicity are now recognized to contribute significantly to the loss of insulin-producing beta-cell function that leads to diabetes and exacerbates cardiovascular disease. However, the molecular and cellular mechanisms by which these processes occur remain unclear. A better understanding of the mechanisms leading to proteotoxicity and islet beta cell failure will provide critical targets for the development of therapeutic strategies to mitigate metabolic disease.

We recently defined the nature of the toxic species produced during amyloid formation by the hormone IAPP (islet amyloid polypeptide or amylin), and identified a novel RAGE-mediated mechanism of IAPP-induced beta cell toxicity that results in glucose intolerance. Building on our findings, my group is using cross-disciplinary approaches to study the factors that influence pancreatic islet beta cell fate. Basic science and translational studies combine experimental techniques in biochemistry, protein biophysics, cell biology and physiology, and aim to:

1) Determine the molecular and cellular basis of islet amyloidosis-induced beta cell dysfunction and death in type 2 diabetes.

2) Define the RAGE-mediated cellular pathways leading to islet cell defects in all forms of diabetes.

3) Investigate the role of endocrine cell cross-talk in beta cell physiology and diabetic complications.

4) Develop protein engineering and rational drug design strategies to treat and prevent proteotoxicity and amyloidosis pathology in a wide range of protein-misfolding disorders including diabetes, Alzheimer’s disease and systemic amyloidosis.

[ List of Publications ]