Project Team: David Standaert, M.D., Ph.D. Ashley Harms, Ph.D. Richard Kennedy, M.D., Ph.D. Jonathan McConathy, M.D., Ph.D. Hongwei Qin, Ph.D. Focus Points: Are inhibitors of the JAK/STAT Signaling Pathway a potential treatment for Parkinson Disease? -How does -syn lead to activation of the JAK/STAT pathway, and how does this contribute to neuroinflammation and neurodegeneration? -How is JAK/STAT signaling status altered in peripheral immune cells from PD patients, and how are these changes related to clinical outcomes? -Can inhibitors of the JAK/STAT pathway prevent neurodegeneration in animal models of PD?

Project Team: Etty "Tika" Benveniste, Ph.D. Richard Kennedy, M.D., Ph.D. Hongwei Qin, Ph.D Focus Points: Are inhibitors of the JAK/STAT Signaling Pathway a potential treatment for Parkinson Disease? -How does -syn lead to activation of the JAK/STAT pathway, and how does this contribute to neuroinflammation and neurodegeneration? -How is JAK/STAT signaling status altered in peripheral immune cells from PD patients, and how are these changes related to clinical outcomes? -Can inhibitors of the JAK/STAT pathway prevent neurodegeneration in animal models of PD?

Project Team: Andrew West, Ph.D. Richard Kennedy, M.D., Ph.D Focus Points: The role of LRRK2 in PD-related inflammatory processes -Does LRRK2 inhibition in the periphery block α-syn driven pro-inflammation and neurodegeneration? -Do macrophages from LRRK2 mutation carriers and early PD patients demonstrate enhanced pro-inflammatory responses to α-syn? -What is the role of LRRK2 activity in these responses?