CIMED has awarded three Pilot and Feasibility grants for 2013

Bess Marshall, M.D.

Associate Professor, Pediatrics


“Sulfonylureas in Type 1 Diabetes”

Sulfonylureas are used to re-establish glucose mediated insulin secretion in individuals with neonatal

diabetes. The mechanisms by which glucose mediated insulin secretion can be altered as a result of genetic

mutations has expanded exponentially by studying the genetic defects of individuals with neonatal diabetes

and hyperinsulinism. We propose a pilot study to evaluate sulfonylurea response in Type 1 Diabetic

participants without diabetes-associated autoantibodies and use gene sequencing to identify genetic

associations in those who have sulfonlyurea response.



Igor Efimov, Ph.D.

Professor, Biomedical Engineering


“Electrophysiology of long-term culture of adult human myocardium”

Genetic manipulation and regulation of ion channel expression has been studied thoroughly in a large variety

of animal models and in cell culture. However, the clinical translation of the results of these studies has been

hampered by significant differences in genetics, cell and tissue physiology between various animal models,

on the one hand, and human patients, on the other hand. Recent advent of iPS cell technology presented

exciting opportunities to study cardiac physiology in human cell lines, including patient-specific iPS cell

derived myocytes. However, it remains impossible to manipulate gene and protein expression in adult

human myocardium. The goal of this project is to produce such a versatile open source platform by using

adult human ventricular slices that can be cultured for at least 1-4 weeks allowing application of viral vector

and RNAi methods to regulate protein expression related to electrical activity in the human myocardium. We

aim to develop and validate this platform, focusing on ion channels, connexins, and calcium handling

proteins as they remodel during heart failure.



Thomas Brett, Ph.D.

Assistant Professor, Internal Medicine


“CLCA1 Regulation of Calcium-Activated Chloride Channels in Chronic Lung Diseases”

Calcium-activated chloride channels (CaCCs) play a central role in airway health and disease. In

homeostasis, they contribute to normal mucus salinity and hydration. However, overactivation of CaCCs in

the airway has been linked to mucus cell metaplasia (MCM), and consequent excess mucus production in

chronic airway diseases. The secreted protein CLCA1 is a potent modulator of CaCCs and its

overexpression drives MCM through an unknown mechanism. Although CLCA1 has long been linked to

asthma and COPD, and considered as a drug target for the treatment of these diseases, progress in this

area has been limited due to the lack of mechanistic insight into CLCA1 function. Understanding of the

structural mechanism by which CLCA1 modulates CaCCs could lead to the design of inhibitors that serve as

anti-mucus therapeutics. In this pilot project, we focus on elucidating the structural and biochemical basis by

which CLCA1 modulates CaCCs.