Research Associate Professor
B.Sc. in Medicinal Chemistry from University of Missouri – Columbia, 2001
Ph.D. in Chemistry (Chemical Biology) from State University of New York – Stony Brook, 2006
National Institutes of Health NRSA (F32) Individual Postdoctoral Fellowships, 2007 – 2008 and 2010 – 2012
Postdoctoral Fellow: Joslin Diabetes Center, Harvard Medical School, 2006 – 2008
Postdoctoral Fellow: Columbia University Medical Center and NYU School of Medicine, 2009 – 2015
Office: 645 Chemistry, Lab: 652 Chemistry, Email: Andisheh.Abedini@stonybrook.edu
Basic and translational research on islet β-cell toxicity, and rational drug design for the treatment of cardiometabolic diseases
Dr. Abedini studies the molecular and cellular basis of diabetes. Her research integrates the use of quantitative in vitro, ex vivo and in vivo experimental methods to uncover mechanisms contributing to pancreatic islet cell dysregulation and metabolic defects. Her work also involves the development of novel biologics for the treatment of diabetes and obesity. The broad aim of her work is to identify therapeutic targets and effective strategies to preserve insulin-producing cells, prevent hyperglycemia, and better regulate body weight.
Prof. Abedini has contributed to the understanding of islet amyloid polypeptide (IAPP or amylin) biophysical chemistry and pancreatic islet amyloidosis biology. The metabolic co-hormones insulin and IAPP/amylin work in concert with each other to maintain energy homeostasis in the body. In diabetes, the dysfunction and loss of insulin- and IAPP/amylin-producing pancreatic islet β-cells leads to metabolic dysregulation and uncontrollable blood glucose levels requiring hormone replacement therapy. Human IAPP/amylin has an extraordinarily high propensity to aggregate in vitro, and forms pancreatic islet amyloid in vivo in the setting of metabolic disease. Islet amyloidosis-induced proteotoxicity contributes to β-cell dysfunction and loss in human diabetes. The mechanism by which IAPP/amylin misfolds and aggregates into proteotoxic species is unknown, and its cellular mechanisms of toxicity are unclear. Dr. Abedini’s work is focused on determining the causes and consequences of IAPP/amylin amyloid formation in vitro and in vivo, and developing new methods for the design of improved, soluble/non-amyloidogenic, bioactive, non-toxic human IAPP/amylin analogs to improve current therapies for human diabetes and obesity.
Dr. Abedini’s work has defined the molecular properties of toxic IAPP/amylin intermediates produced during amyloid formation and linked their distinct features to induction of β-cell/islet stress, inflammation, dysfunction, and apoptosis. These key insights facilitated her discovery of a new receptor-mediated mechanism of islet amyloidosis-induced β-cell toxicity in pre-diabetes, opening up new avenues for hypothesis-testing and translational research in cardiometabolic disease. Dr. Abedini has also developed efficient methods for the chemical synthesis and purification of highly aggregation-prone, post-translationally modified, bioactive polypeptides, including IAPP/amylin; the detection and characterization of their various non-toxic and toxic amyloidogenic species; and the development of time-resolved assays that draw links between physicochemical and biological properties of proteins. This work has led to the discovery of several new inhibitors of amyloid formation and cytotoxicity.
In recent years, Dr. Abedini and colleagues have developed and validated a novel approach for re-designing polypeptides to improve their solubility, while retaining their activity. This work enabled their generation of soluble, bioactive, non-toxic analogs of human IAPP/amylin that can be co-formulated with commercial insulins and other agents to improve therapies for diabetes and obesity. Translational research projects in her lab focus on biomarker discovery, and development of novel biologics and bio-based diagnostic tools for the treatment of cardiometabolic diseases.