Research Projects
What are the molecular mediators of neuronal mitophagy?
One of the major mechanisms utilized by cells to remove aged and/or damaged mitochondria is the selective removal of the organelle via autophagy, better known as mitophagy. Much research in the past decade examining mitophagy has been performed in transformed cultured cell lines, and has yielded the general cascade of events that occur in the mitophagic process (see illustration below). With modern genetic tools and recent discoveries, we are now in a place to systematically dissect the molecular mechanisms regulating mitophagy in neurons in vivo. We are taking a two step approach in: 1) identifying candidate genes involved in mitophagy in neurons, and their contribution to the mitophagic process; and 2) understanding the physiological consequences of disrupting neuronal mitophagy. We primary carry out these experiments in fruit flies, which have significantly less genetic redundancy in the molecular machinery executing the different forms of mitophagy (see below).
How do disruptions in mitophagy contribute to other diseases?
We are interested in the process of mitophagy in biological contexts associated with disease. Disruptions to mitophagy have been linked to many other diseases, and we are interested to dig deeper into the cell biological and physiological defects associated with these diseases. We plan to model such mitophagy-associated diseases in the fly, cultured cells, and rodents.
How do autophagy adaptor proteins influence protein aggregates in neurodegenerative diseases?
In a new project in the lab, we are determining the role of autophagy adaptor proteins in the degradation of protein aggregates in neurons in vivo utilizing the powerful genetic tools available in fruit flies. Using our approach, we can assess alterations at the cellular level through the organism physiology to determine potential mechanisms of disease supression or enhancement.