Hund receives 1.6M R01 award from the NIH/NHLBI

Thomas Hund, PhD, Professor in the Department of Biomedical Engineering and Associate Director, Davis Heart and Lung Research Institute, was recently awarded a $1.6M three-year National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), R01 award entitled Role of TREK-1 in modulating cardiac excitability and arrhythmias. The award runs March 1, 2021 – February 28, 2024.

Project summary: Cardiac electrical rhythm disturbances (arrhythmias) contribute to over 500,000 deaths each year in patients with cardiovascular disease (CVD). Despite considerable advances in defining the specific cell- and organ-level remodeling changes associated with CVD, the precise mechanisms driving increased susceptibility to arrhythmia remain to be defined. At the same time, existing anti-arrhythmic therapies are limited by efficacy, low patient tolerance, risk of procedural complications, and/or cost. In particular, the development of new anti-arrhythmic drugs has been hampered by high profile failed clinical trials involving compounds that target major cardiac ion channels, leading to a shift away from the pursuit of population wide, “blockbuster” therapies and towards more precise, patient-specific approaches. Essential for this effort will be the development of novel adjuvant therapies that tune cardiac excitability without introducing large scale perturbations in the cardiac action potential. Here, we explore the two-pore K+ channel TREK-1 as an ideal, although understudied, candidate for next generation “precision” therapeutics based on: 1) endogenous expression in cardiomyocytes across species, including mouse and human; 2) multiple regulatory modes for tuning of channel activity; and 3) recent emergence as a highly druggable target. The central hypothesis of this proposal is that TREK-1 functions as a multimodal stress sensor in heart, as well as therapeutic “lever” that may be tuned to modulate cardiac excitability through association with the spectin-based cytoskeleton.

Project co-investigator and collaborators are Krishna Chinthalapudi, PhD, Assistant Professor, Physiology & Cell Biology; Isabelle Deschenes, PhD, Professor and Chair, Physiology & Cell Biology; Peter Mohler, PhD, Professor, Physiology & Cell Biology and Internal Medicine.

Congratulations Dr. Hund and team!