We are focused on a few major questions:
1. What are the roles of TMEM184b in axon degeneration and synapse maintenance? We are using both fly and mouse mutant animals to ask questions about synaptic transmission, axon transport, and autophagy control by the 7-pass transmembrane protein and putatitve GPCR TMEM184b. We are also using transcriptomics and proteomics to investigate TMEM184b pathways. We can study the role of TMEM184b in axon degeneration in vivo in the peripheral nerves, specifically in the context of diabetic or chemotherapy-induced neuropathy.
2. How does the progression of axon degeneration relate to the initiation of pain and numbness in chemotherapy-induced peripheral neuropathy (CIPN)? CIPN is the dose limiting side effect of the cancer treatment drugs paclitaxel (taxol) and vincristine, and this neuropathy causes patients to discontinue their use, limiting the effectiveness of their cancer treatment. We are using behavior and optogenetics to pursue these questions in the fruit fly Drosophila melanogaster and hope to use this knowledge to identify ways to treat painful neuropathy by blocking the underlying dendrite and axon degeneration.
3. How well does our current knowledge of axon degeneration pathways apply to the early stages of neurodegenerative disorders in humans? It has been suggested based on human neuroimaging that white mater injury is an early event in the pathogenesis of Alzheimer's and Parkinson's disease. One major protein implicated in CNS neurodegenerative disease is tau, an axonal microtubule-associated protein. We would like to investigate the links between changes in tau and degeneration of axons under pathological conditions in mouse or human neurons.