Parkinson's Disease (PD) is a progressive neurodegenerative disorder that impacts millions of individuals worldwide, with no cure currently available. Although PD is characterized for its motor symptoms, it is a whole-brain and whole-body disease, manifesting a wide range of non-motor symptoms, including gastrointestinal dysfunction and cognitive impairment. Accumulation of α-synuclein protein, a hallmark of PD pathology, is found in specific brain regions but also in other peripheral tissue, disrupting cellular function and triggering neurodegeneration.

Understanding why certain cells and brain regions are particularly vulnerable to develop α-synuclein pathology and PD-associated neurodegeneration plays a key role in developing more effective treatments. Additionally, investigating how the microenvironment in these affected areas changes—and how these changes contribute to or exacerbate the disease—offers valuable insights for advancing our understanding of PD. By identifying the cellular and molecular mechanisms driving vulnerability and resistance, we aim to identify therapeutic targets that could modify the course of the disease and improve outcomes for individuals living with PD.

A cornerstone of our research involves detecting and mapping PD pathology in the brain. Our lab has extensive expertise in developing and employing experimental models of pathology. We make use of a variety of techniques to induce PD-like pathology, including transgenic mice, viral vector-mediated gene delivery systems (e.g., Designer Receptors Exclusively Activated by Designer Drugs, or DREADDs), and toxin-based methods. These approaches enable us to replicate the different aspects of PD pathology and its progression. Our research utilizes cutting-edge detection techniques to systematically assess which neuronal subtypes are most prone to accumulating pathology. We also investigate the downstream effects of this pathology, encompassing both cell-autonomous processes (within affected cells) and non-autonomous effects (impacting surrounding cells). We take a comprehensive and integrated approach to detect and investigate these effects. Using methodologies such as immunohistochemical analysis, in situ proximity ligation assays, and stereological assessments of neurodegeneration, we quantify the extent and impact of pathology. The complementary omics analyses provide a comprehensive view of molecular changes, offering insights into cellular responses to PD-related stressors and identifying novel targets for intervention.