Dr. Jayanta Debnath’s lab is recognized for its expertise on how autophagy, a fundamental catabolic process in which a cell literally “eats itself,” regulates epithelial cell fate, oncogenic transformation, and carcinoma progression. In cancer, our current understanding is that autophagy serves multifaceted roles in tumor initiation and progression. Although genetic evidence corroborates a critical role for autophagy as a suppressor of tumor initiation, autophagy also functions as a survival pathway in advanced tumors during stress, which has important implications for progression and metastasis.
The laboratory focuses on two broad goals: 1) delineate the multifaceted roles of autophagy in adhesion-independent survival and oncogenic transformation in vitro as well as on breast cancer progression and late recurrent metastatic disease in vivo; and 2) dissect the biochemical and in vivo physiological functions of the molecules that control autophagy (called ATGs) to ultimately exploit this process for therapeutic benefit.
To date, the major research accomplishments of Dr. Debnath’s lab include: 1) the discovery that autophagy is strongly induced in epithelial cells deprived of extracellular matrix (ECM) contact, which protects cells from detachment-induced cell death (anoikis); 2) the first demonstration that detachment-induced autophagy promotes anchorage-independent transformation by facilitating glycolytic metabolism (the “Warburg effect”); and 3) the identification of a novel complex between two autophagy conjugation pathway components, ATG12 and ATG3, that unexpectedly directs mitochondrial homeostasis and apoptosis, thus implicating these canonical autophagy regulators in biological processes other than autophagy.