Research Areas

Autophagy and Mitophagy

Researchers in the Gottlieb Lab are exploring the roles of autophagy and mitophagy in the heart in both health and disease settings. We have found that autophagic removal of damaged mitochondria (mitophagy) is important for protecting the heart against ischemia/reperfusion injury. Interventions such as ischemic preconditioning and statin therapy activate mitophagy that depends on the participation of specific proteins, including Parkin and p62/sequestosome1, and on depletion of coenzyme Q10. We have developed tools for studying mitochondrial turnover, notably a fluorescent protein we call MitoTimer. Recent work has led us to understand that the heterogeneity of MitoTimer maturation from green to red is in part a reflection of differences in fuel utilization in the heart, revealing a new aspect of cellular heterogeneity.

Impact of Obesity on Autophagy and Cardioprotection

The Gottlieb Laboratory is interested in understanding how metabolic syndrome disrupts autophagy and increases ischemia/reperfusion injury in the heart, using cell, mouse and porcine models. One of our goals is to identify agents that can restore autophagy and cardioprotection. Using proteomics to develop a detailed portrait of the heart in animals fed standard chow or a high-fat diet, we have discovered that obese mice show remarkable dysregulation of the response to nutrient stress that may parallel and shed new light on their exaggerated response to ischemic stress.

This confocal image of a heart cryosection from a mouse expressing MitoTimer reveals evidence of synchronized mitochondrial turnover among neighboring cardiomyocytes. This novel tool animal allows us, for the first time, to visualize mitochondrial turnover in vivo.

Cardiomyopathy in Stem Cell Depletion Syndromes

Mitochondrial Function in Health and Disease

Using Seahorse respirometry and a variety of complementary approaches, the Gottlieb Laboratory is analyzing mitochondrial function in various disease states. We are studying mitochondrial alterations in biopsies from heart transplant patients, with the goal of identifying early markers that will predict graft rejection. This work is done in collaboration with Lawrence Czer, MD, and the heart transplant team.

Contact the Gottlieb Lab

127 S. San Vicente Blvd.
Pavilion, A9100
Los Angeles, CA 90048