I am a neurologist and neuroscientist with interests in neurodegenerative diseases, protein aggregation, and mechanisms underlying neuron injury and death. My long term goal is to better understand the molecular events that influence the pathological aggregation of disease-associated proteins contributing to dementia in Alzheimer disease (AD) and Parkinson disease (PD). There is substantial overlap between these two common neurologic diseases including at the molecular level. Aggregated forms of amyloid beta (Ab), tau, and alpha-synuclein (aSyn) proteins accumulate in the brain in patients with dementia in both disorders, but to different extents and with distinct neuro-anatomic patterns.
Furthermore, some studies indicate that Ab, tau, and aSyn may act synergistically to initiate or propagate aggregation of one another, a process termed “cross-seeding.” Less is known, however, about the mechanism by which this phenomenon occurs, and it is possible that shared mechanisms exist that may regulate the aggregation of multiple proteins across different diseases. By combining data from genetic risk studies, in vitro and cell-based assays of protein aggregation, and in vivo models of protein aggregate spreading along neuroanatomically relevant networks, I hope to define the molecular regulatory mechanisms governing the pathological aggregation of disease-associated proteins. Ultimately my goal is to leverage this understanding to help guide the development of disease-modifying treatments for AD and other neurologic disorders that cause dementia.