Immune System Aging in Parkinson’s and Alzheimer’s disease: Epigenetics, biologic aging, and heightened immune states in a population-based study

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PROJECT ABSTRACT. Kimberly Paul, PhD, MPH, is a neurologic and aging disease epidemiologist whose research career goals focus around using modern, “omic” technologies to define the neurodegenerative disease process and elucidate risk at a biologic level, integrating a systems biology approach, in population-based studies. The research she proposes, entitled “Immune System Aging in Parkinson’s and Alzheimer’s disease-related dementia: Epigenetics, biologic aging, and heightened immune states”, combines advanced statistical methods and a systems biology modeling approach with high-throughput omics markers to study immune system aging in neurodegenerative disease patients relative to community-based controls; followed by relating epigenetic markers of inflamm-aging to symptom development and multiple metabolomics measurements over time. Candidate & Mentoring Team: Dr. Paul is a Postdoctoral Scholar in the Department of Epidemiology at the Fielding School of Public Health (UCLA) and will transition to an Assistant Professor in the Department of Neurology, David Geffen School of Medicine. Dr. Paul was previously awarded an NIEHS F32 to investigate how metabolic dysfunction mediates the association between ambient environmental exposures and primarily Alzheimer’s disease-related dementia (ADRD). For this work, she was awarded the prestigious Chancellor’s Award for Postdoctoral Research at UCLA. Her research priorities have developed into bringing biology and mechanism into population and data science. The proposed career development plan will build upon her previous training with goals to enhance her trajectory toward becoming an independent investigator, including experiential and didactic learning in design, methods and data interpretation, while developing the leadership and professional skills required to lead an independent research lab and execute an R01. Dr. Paul has assembled a strong mentoring team with renowned expertise, commitment, and available resources to support her training. Research Summary: The research aims of this K01 proposal focus on using a systems biology pipeline to investigate immune system aging in Parkinson’s disease (PD) and ADRD patients, using blood-based epigenetics to define immune states. The purpose of this proposal is to investigate how these immune markers and measures of accelerated immune system aging relate to onset, symptom development, and trajectories of metabolomic changes using two population-based studies. The hypothesis being that immune profiles which reflect “inflamm-aging” (chronic, low-level inflammation states) and immunosenescence will be related to faster symptom development. Furthermore, longitudinal metabolomics and targeted gene sequencing will give insight into endogenous risk and the systemic response related to different immune states as symptoms develop. This award will provide Dr. Paul the research opportunity and career development resources to continue to excel and establish herself as an independent investigator and leader in her field, conducting innovative research, combining systems biology, omic technologies, and population-based research.