Pesticides commonly used by gardeners and found on the shelves of garden centers are increasingly associated with an increase in PD risk. Well-established epidemiology studies combined with in vitro and in vivo experiments suggest that the mitochondrial complex I inhibitors and oxidative stressors pesticide increases the risk of PD. Nevertheless, not all those who are exposed to pesticides develop PD. The identification of genetically susceptible and resilient populations is urgently needed, and studies understanding the gene - environment interaction will fulfill these needs. Mitochondria dysfunction plays a key role in PD pathology. However, to date, few studies have thoroughly examined the functional roles of mtDNA variants in PD or the therapeutic potential of mitochondrial-derived peptides (MDPs) in these conditions. In this study, we will investigate the influence of the mitochondrial DNA variant on PD risk and progression of motor and non-motor symptoms in population-based studies. Further, we will explore how the SHLP2 DNA variant modifies the risk of PD associated with exposure to pesticides in a well-established PD mouse model.

Recent technical advancements enable high-throughput genome sequencing feasibility in the clinic. Personalized medicine can allow physicians to accurately predict the treatment and prevention strategies that will work for their patients. The proposed project will provide a personalized medicine strategy on diagnosis, treatment, and prevention by determining the association between mitochondrial genetic variants and PD-related outcomes. Another MDP, MOTS-c, was identified and published in 2015 and now is in clinical trial phase 1 for non-alcoholic fatty liver disease, which serves as a proof-of-concept for the proposal presented here. Once the therapeutic potential of SHLP2 for PD is identified in the proposed study, a genetic analysis will facilitate SHLP2 analog development for potential PD interventions and personalized medicine.

I am convinced that the unique training, experiences, and networking opportunities obtained from this award will become a crucial stepping stone for my career as an independent researcher in the field of PD. The collaboration with the Advisory Committee Members is a great opportunity to improve my science project and produce meaningful findings for the scientific and clinical community. The work supported by this fellowship will be a solid foundation for an NIH funding opportunity after completing the award.