Jason Wu, PhD: What’s Brewin’ in Your Lab?

Jason Wu, PhD: What’s Brewin’ in Your Lab? 

The Southwest Environmental Health Science Center (SWEHSC) recently hosted a “What’s Brewin’ in Your Lab” session featuring Jason Wu, PhD, Assistant Professor of Physiology, and Jing Liu, PhD, Assistant Research Professor, who collaborate in their research on the effects of per- and polyfluoroalkyl substances (PFAS) exposure on kidney and  cardiovascular health. Their research programs are funded by NIDDK, American Heart Association, American Society of Nephrology, and the SWEHSC pilot award program. 

Wu’s research focuses primarily on investigating how the kidneys regulate blood flow and electrolyte balance, as well as examining renal mechanisms in hypertension and chronic kidney disease. His lab is particularly interested in exploring the susceptibility of these processes to oxidative stress and environmental toxicants such as PFAS. The current research explains and explores the mechanistic effects of chronic PFAS exposure on kidney inflammation, glomerulosclerosis (scarring of the kidneys), and abnormalities in renal electrolyte transport.  

While Liu’s previous research focused on understanding the roles of lipoproteins in atherosclerosis and aneurysms, the regulation of vascular remodeling and metabolism through microRNAs, and the molecular and cellular mechanisms involved in kidney function and blood pressure control,  her current work focuses on how PFAS exposure may contribute to dyslipidemia and  kidney metabolic dysfunction. Liu is also examining how genetic variants in PFAS-excreting transporters may affect the susceptibility to hypertension, microvascular dysfunction, kidney dysfunction, and chronic kidney disease. 

PFAS are man-made chemicals widely used since the 1940s, known for their water and stain-resistant properties. They are contained in many of our everyday objects, such as non-stick cookware, microwave popcorn bags, fast-food packaging, and cosmetics. The primary routes of PFAS exposure include ingestion through contaminated food, water, or consumer products. According to the National Health and Nutrition Examination Survey (NHANES), 98% of Americans have PFAS detected in their body. The even more alarming aspect of this fact is that once PFAS enter the body, their serum half-life is 3 to 8 years. This means that even for those who were once exposed and have stopped being exposed, it takes a long time for the PFAS to leave their body. In the natural environment, PFAS have a lifespan of around 50,000 years, fulfilling their nickname as “forever chemicals”. PFAS are detected in 45% of U.S. drinking water samples, including those from rural wells, posing an even greater risk of water contamination to Arizona residents already dealing with water scarcity.  

PFAS affect almost every organ in the body, associated with cardiovascular disease, kidney disease, liver disease, metabolic syndrome, reproductive disorders, immune dysfunction, and cancer. Wu’s lab focuses on the impact on the kidneys and cardiovascular healthin response to the statistics surrounding the prevalence of hypertension in the United States. Hypertension (high blood pressure) affects several areas of the body, including the kidneys, central nervous system, and blood vessels. 46% of the U.S. adult population has overt hypertension, and by the age of 70, 70% of the population is affected. Some studies, using data from the NHANES, have identified a positive correlation between high blood pressure and PFOA, a specific type of PFAS. Other studies examining PFAS in drinking water have also shown a positive correlation between high blood pressure and PFOA, with even small concentrations of PFAS causing a profound effect.  

The main objective of Wu’s research is to directly test the effects of chronic PFAS exposure on blood pressure and kidney function in mouse models. To test this objective, Wu employs various laboratory procedures, such as radiotelemetry for blood pressure monitoring, wire and pressure myography to examine small blood vessels, and a transonic flow meter system to measure renal blood flow and renal vascular resistance. Notably, instead of studying just one type of PFAS, his team adopts a mixed model to study the interactions of several types, better reflecting how people are exposed in real life. 

Liu researches how PFAS exposure affects kidney function and why certain individuals are more susceptible. To explore this, Liu has identified a common genetic variant in a PFAS efflux transporter. When this transporter is compromised, it cannot effectively remove PFAS from the body. Liu hypothesizes that people carrying this variant clear PFAS less efficiently, making them more susceptible to kidney damage and adverse cardiovascular effects. Together, their research will increase understanding of how PFAS exposure affects human health, specifically in the  kidney, and ultimately explore therapeutic agents that can reduce cardiovascular and renal toxicity.