Augustine Sobo – UMass Fellow 2024-2025
Research Progress: I am a second year PhD student in the Timme-Laragy lab where I study the effects of developmental perfluorooctanesulfonic acid exposure on pancreatic islet vascularization in zebrafish (Danio rerio). Perfluorooctanesulfonic acid (PFOS) is a member of a group of man-made organic compounds known as Per- and polyfluoroalkyl substances (PFAS). This chemical is characterized by fully substituted fluorinated atoms making it resistant to hydrolysis. As a result, they are widely used in the manufacturing processes of several products, including non-stick materials, water repellent coating, cleaning products and firefighting foams. PFOS is a ubiquitous environmental contaminant found in >98% of human serum samples tested. Animal studies and epidemiological studies have linked PFOS exposures to several adverse health effects including metabolic dysfunction. Recently, research in our lab has shown that embryonic exposure to PFOS caused aberrant islet morphology and disrupted pancreatic organogenesis in zebrafish. Vascularization of the islets is essential for β-cell physiology since it keeps islets in close proximity to blood to detect changes in glucose levels. This also renders the islets vulnerable to toxicants like PFOS found in systemic circulation. As a result, we aim to understand the mode of toxicity of PFOS by assessing its effects on vascularization of islets as a potential contributor to the altered islet development with developmental PFOS exposure.
To study this, our lab generated a transgenic fish line which expresses fluorescent proteins in the endothelial cells (green) and pancreatic β-cells (red), respectively. Over the past year, I have honed my confocal microscopy skills by using the Nikon AXR NSPARC confocal microscope at the Nikon Center of Excellence in the UMass light microscopy core facility to image exposed fish to analyze islet vasculature. We have found that PFOS exposure significantly decreased the contact points between vasculature and islets. Single cell RNA sequencing data generated from the lab showed a down regulation of integrin gene expression in PFOS exposed fish. Since changes in integrin expression have been shown to affect insulin release, I am currently looking at exposing fish to known integrin inhibitors to investigate the effect of integrin inhibition on vascularization of the islet. With this, I hope to understand if PFOS reduces vascularization via inhibiting integrin activation and if that affects β-cell function in the fish.