The Dawson lab studies neuronal cell death and survival, the molecular underpinnings of Parkinson’s disease and the development of neuronal stem cells. The lab has named a new cell death process Parthanatos. In the brain, Parthanatos is important in ischemic and excitotoxic injury and in models of Parkinson’s disease. The cell death mechanism involves nuclear activation of poly(ADP-ribose) polymerase and mitochondrial release of apoptosis inducing factor in the integration of the death signal; current research aims to further understand how this pathway works. In addition to cell death, the team also strives to understand how cells survive by characterizing survival genes and proteins involved in preconditioning. The team uses induced pluripotent stem cells to identify pharmaceutical agents that might be used therapeutically to protect the brain.

To understand the role of LRRK2 in the function and dysfunction of neurons and in Parkinson’s disease, the team has generated LRRK2 knockout mice and LRRK2 transgenic mice to identify and characterize the interaction of LRRK2 and its protein targets through state-of-the art protein biochemistry with the hope if finding new strategies to treat PD.

The team also is studying Notch and Botch signaling in human neural precursor cells differentiated from human embryonic stem cells to understand how Botch and Notch signaling leads to differentiation and maturation of the nervous system as well as regulation of adult neurogenesis which is thought to be important for learning and memory and which is thought to be impaired following stroke. Studies are underway to determine if regulation of Botch and Notch signaling can promote survival and repair following stroke.