David Ron, MD

Medicine (Skirball Institute) – Primary Mentor

Dr. Ron is an expert in the biology of the cellular response to stress. In addition to fundamental work on the adaptations cells undergo in response the threat of protein misfolding in the endoplasmic reticulum, his lab is engaged in two translational programs in cardiovascular medicine. The first concerns the role of endoplasmic reticulum stress in lipid metabolism and is conducted in collaboration with Dr. Fisher’s lab. The second project concerns the role of endoplasmic reticulum oxidation in the progression of heart failure and examines the hypothesis that a less oxidizing ER may be associated with protection. Endoplasmic reticulum stress and functional hypoxia, which are known to occur in cardiac muscle during the progression of heart failure, promote activation of the gene encoding the alpha isoform of the ER oxidase, ERO1a and are predicted to lead to a hyper-oxidized ER. Gene targeting in mice was used to create a null allele for ERO1a, which is viable and healthy in the homozygous state. In collaboration with Dr. Fishman’s laboratory, the Ron lab has begun to study the impact of the ERO1a mutation on the progression of heart failure in the mouse trans-aortic compression model. In a parallel strand, an in vitro miniaturized assay for ERO1 has been developed and HTS screening for inhibitors has begun. In a favorable scenario these may, one day, be developed into novel cardiac therapeutics.