The Gottlieb Laboratory, led by Roberta A. Gottlieb, MD, is studying the cell biology of ischemia/reperfusion injury in cell and animal models, with the ultimate goal of developing treatments that can be adopted in the clinical setting. Until recently, many treatments have appeared promising in animal models but have failed in human trials because the models were not representative; that is, the models did not have comorbidities such as obesity, diabetes or advanced age. Using more appropriate animal models, we have found that a process called autophagy plays a central role in the heart's tolerance to ischemic injury. Autophagy, or intracellular recycling, is diminished in aged animals or in those that develop diet-induced obesity and glucose intolerance. Our lab is developing ways to modulate autophagy and restore its beneficial activity in the diseased heart. Autophagy plays a critical role in eliminating damaged mitochondria.
This stylized image shows two colorful mitochondria, one engulfed by an autophagosome (purple). The mitochondrial cristae — the numerous infolded membranes carrying the electron transfer complexes — are arranged in a thumbprint pattern based on Gottlieb's own mother's thumbprint. This is appropriate because mitochondria are maternally transmitted. The pink dots represent glycogen granules, which supply glucose for oxidative phosphorylation and which can also be engulfed by autophagosomes, and a bit of endoplasmic reticulum (lavender) is associated with the mitochondria to signify their close interaction for calcium exchange.