Idiopathic diseases (particularly neuro-degenerative and oncologic) continue to make diagnosis and treatment difficult due to their undefined nature. Many of these diseases have a heritable component, and for some, it is the primary underlying etiology. With Whole Exome Sequence from a variety of patients, the identification of a large set of putative disease-causing variants is feasible. The remaining issue is to definitively identify the small set of variants that are truly causative in these polygenic conditions. We utilize new precision medicine pipelines to functionally test combinations of variants in cellular systems.

In the neurosciences, axon degeneration and regeneration are the cellular consequences of debilitating neuropathies and traumatic injuries to the brain and spinal cord.  We and collaborators seek to understand the biological pathway that controls degeneration and regeneration in these important cells.

Glaucoma is a subset of neurodegenerative diseases and is extremely common in the US, but the molecular correlates leading to the optic nerve dysfunction is unclear.
Auditory systems in animals consist of a cache of modules which can each be damaged in explosive scenarios or in a number of disorders. We are exploring the role of neuropathy in both Glaucoma and Noise-Induced Hearing Loss.

In adult cancers, seemingly normal cells respond inappropriately to stress by proliferating and becoming refractory to apoptosis. These cells can be thought of as in a continual state of repair, attempting to heal a wound which they-themselves are creating. Autophagy is one of the cellular processes which is active when cells are in this state-of repair.  Investigating the connections of autophagy after stresses chemotherapy and chronic inflammation will be important to determine how the cells are adapting to these stresses and at which point in the chain of interacting cells is the benefit acquired.