The task is not to see what has never been seen…but to think what has never been thought…about what you see everyday.– Erwin Schrodinger
In the Towers lab we study cellular recycling processes in cancer cells. In one such mechanism – Autophagy – double membrane vesicles target cytoplasmic material for degradation via the lysosome. This process is important in many cancer cells as they must be able to recycle their own nutrients to support cellular metabolism when growing in nutrient poor environments like a solid tumor. Moreover, autophagy is also important for clearing damaged organelles and other macromolecules to maintain cellular homeostasis. Pharmacological agents to target these pathways are moving forward in clinical trials to treat a variety of different types of cancer, however initial results have been lukewarm. We discovered that cancer cells can adapt to autophagy inhibition and co-opt other cellular processes to survive.
We are interested in the specific mechanisms autophagy-dependent cancer cells can employ to maintain organelle homeostasis and generate nutrients when autophagy is blocked. In particular, how can cancer cells avoid the buildup of damaged proteins or mitochondria – two molecules autophagy is necessary for the clearance of – when autophagy is inactivated? How do cancer cells adapt in this context? Do these mechanisms of adaptation predict patient response to autophagy inhibition? Can we target these adaptations to improve cancer patient outcome?
If we knew what it was we were doing, it would not be called research, would it?– Albert Einstein
We use multi-disciplinary cell biology and molecular biology techniques including genome-wide CRISRR/Cas9 editing, super resolution microscopy, optogenetics, and biochemistry to study autophagy in cancer models including cultured cell lines, patient and mouse derived 3D-organoids, and genetically engineered mouse models. The goal of our work is to identify compensatory mechanisms of autophagy-mediated degradation in order to design better targeted therapies to decrease tumor relapse and increase cancer patient survival.