Projects

Building a Multiplex Model to study the interaction among the genome and exposome

Various environmental factors, including exposure to pesticides, nicotine, and caffeine, have influenced Parkinson's disease (PD) etiology and pathogenesis. Recent genome-wide associated studies (GWAS) have identified approximately 100 candidate genes that modify the risk of developing PD. Furthermore, α-synuclein aggregation is a common pathological hallmark of PD. Given the plethora of evidence from epidemiological, GWAS, and post-mortem pathology studies, there is a polygenic interaction with environmental factors. Due to the lack of a suitable model system, these interactions among multiple genetic and environmental risk factors have not yet been studied. Drosophila, in combination with induced pluripotent stem cell (iPSC) derived neurons, as a model system, has immense untapped potential to be used as a tool to study gene-environment interactions. We have developed a multiplex platform to screen for gene-environmental interactions. 

Non-cell autonomous neurodegeneration in response to neurotoxic agents

Metal exposure is increasingly being recognized as a key environmental contributor to chronic neurological diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Glial cell activation and neuroinflammation are key pathophysiological hallmarks of these neurodegenerative disorders, but the mechanism of this non-cell-autonomous neuronal loss is not well understood. In particular, occupational and environmental exposure to manganese has been shown to cause a PD-like disease. We and others have shown that overexposure to the environmental metal Mn induces astrocytic pathology, including gliosis and classical reactive astrocytes, leading to the production of pro-inflammatory cytokines and signal transduction mediators both in vitro and in vivo, suggesting environmental stressors can modulate glial cells to contribute to the pathogenesis of neurodegenerative diseases.

Multi-omics approaches to identify novel mechanistic insights in response to neurotoxic insults

Per- and poly-fluoroalkyl substances (PFAS) are synthetic organofluorine chemical compounds that have been used widely in various applications. Recent studies have shown that various PFASs are involved in liver damage and fertility issues, among others. But very few studies have demonstrated the long-term effects of PFAS on the brain. Using multi-omic approaches (proteomics, high-resolution mass spect), as well as genetic screens, we aim to understand the role of these classes of compounds on brain health.