Anath-ShalevDirector, UAB Comprehensive Diabetes Center

Professor
Department of Medicine
Division of Endocrinology, Diabetes & Metabolism


Contact Information

Office Address: Shelby 1206
Phone: 205-996-4777
E-mail: shalev@uab.edu


Education:

University of Basel Medical School, Switzerland


Post-Graduate Training:

Residency in Internal Medicine, University Hospital of Basel, Switzerland

Postgraduate Scholarship in Experimental Medicine and Biology, University of Zurich, Switzerland

Research Fellowship, Brigham and Women’s Hospital, Harvard Medical School, Boston

Fellowship in Endocrinology, Diabetes and Metabolism, NIDDK, National Institutes of Health, Bethesda


Research Interests:

Molecular biology of diabetes, islet biology, pancreatic beta cells, regulation of gene expression, diabetes drug discovery, translational diabetes research


Research Description:

Diabetes is a rapidly growing public health issue characterized by elevated blood glucose levels and high morbidity and mortality. Under normal conditions, a perfect balance of insulin and glucagon, both produced in the pancreatic islets, maintains blood glucose levels within the normal range. Disruption of this balance such as by loss of insulin-producing beta cells and/or excessive glucagon production is a key feature of diabetes. However, the mechanisms and factors involved are not well understood. Dr. Shalev’s laboratory identified thioredoxin-interacting protein (TXNIP) (a protein involved in the cellular redox state) as such a potential factor. When performing the first human pancreatic islet microarray study, Shalev discovered that TXNIP was the most dramatically up-regulated gene in response to glucose, suggesting that it might play an important role in islet biology. The Shalev group went on to show that TXNIP expression is increased in the islets of mice and humans with diabetes and that TXNIP overexpression induces beta cell death and dysfunction. Moreover, the Shalev lab found that genetic or pharmacological inhibition of TXNIP expression was able to rescue mice from type 1 and type 2 diabetes proving that TXNIP represents an attractive therapeutic target. Indeed, Shalev and her team conducted a randomized clinical trial in subjects with recent onset type 1 diabetes and found that treatment with verapamil, an approved blood pressure drug they had discovered was able to lower TXNIP levels, resulted in significantly better beta cell function and insulin production as compared to placebo. The team has also been working on more specific approaches to inhibit TXNIP and on elucidating the molecular mechanisms and signalling pathways involved in TXNIP regulation and function and is employing molecular biological in vitro approaches, cell culture systems and various in vivo mouse models as well as human islets to do so.

Publications

 

DRC Membership Category:

Senior Scientist