About
Assistant Professor
Department of Medicine,
UCLA
Project Title: Intestinal Mitochondrial Dysfunction and the Gut-Brain-Immune Axis in Models of Parkinson's Disease
Mentors:
Nigel Maidment, PhD – UCLA
Lin Chang, MD – UCLA
Million Mulugeta, DVM, PhD – UCLA
Martin Martin, MD, PhD – UCLA
Multidisciplinary Expertise:
Parkinson’s Disease, Neurogastroenterology, Neuroscience, Mitochondria
Project Description:
Parkinson’s Disease (PD) may begin in the gastrointestinal (GI) tract. The overall goal of this research is to identify intestinal pathogenic mechanisms in PD that may lead to the identification of gut-biomarkers for early diagnosis as well as gut-directed therapies to halt progression of disease in the premotor phase. The proposed research addresses the hypothesis that mitochondrial dysfunction in the intestinal epithelium causes PD via the gut brain immune axis through two specific aims. The first aim will determine the role of mitochondrial dysfunction in mediating the response of the intestinal epithelium to pathologic α-Synuclein. This will be accomplished through measurement of inflammation and mitochondrial stress in duodenal tissue, isolated crypts and intestinal organoids from a PD model. The second aim will test the hypothesis that impaired mitophagy in the intestinal epithelium causes persistent central pathology and motor deficits in a gut-seeding PD model. This will be accomplished through duodenal injection of α-Synuclein preformed fibrils in mice with intestinal epithelial-specific Parkin knockout and wild type mice.