We are interested in what occurs at a molecular level when neurons are in the earliest stages of neurodegenerative disease. In particular, we study the processes of early axon degeneration and synaptic dysfunction and loss, which occur before neurons die. Molecular pathways activated in these neurons, and their communication with nearby non-neuronal cells, promotes disease progression and ultimately disconnects regions of the brain and peripheral nervous system from one another. We are looking for the earliest events that signal disease states, and hope to find ways to reduce or prevent these processes from occurring.
Our work has extremely broad applications ranging from Chemotherapy-Induced Peripheral Neuropathy (a primarily sensory neuropathy), Amyotrophic Lateral Sclerosis (ALS, a motor neuron disease), spinal cord injury, and diabetic neuropathy, all the way to late-onset CNS dementias including Alzheimer's Disease, Parkinson's Disease, and Frontotemporal Dementia. As such, this work has received funding from numerous public and private sources including cancer research foundations, the Muscular Dystrophy Association, and the NIH/NINDS.
We take advantage of two model systems in the lab: the fruit fly (Drosophila melanogaster) and the mouse (Mus musculus). Each has distinct advantages that enable our dual organism approach to be entirely complementary and will help drive new discoveries. Shown below are terminals of some of our favorite neurons: motor neurons responsible for body movement, and sensory terminals responsible for detecting touch and temperature.