2022 Pilot Project Awards
Interdisciplinary Pilot Project Award:
Principal Investigator: Anna Gumpert, Ph.D.
Collaborator: Daniel Conklin, Ph.D.
Title: "Combined Effects of Air Pollution and Hypertension on Cardiovascular Remodeling"
Description of Project: Air pollution is ubiquitous, and exposure to air pollution is associated with 200,000 excessive deaths yearly in the U.S., of which the majority (60–80%) is due to cardiovascular disease. Although air pollution is typically higher in urban centers, unique sources of air pollution including particulate matter (PM) and gases (volatile organic compounds) can occur anywhere. One such phenomenon was observed in the past few years when widespread wildfires throughout North America contributed to increased air pollution both locally but also at distant locations. Additionally, rurally located industrial sources of air pollution can disproportionally contribute to local air pollution, as witnessed by the hemp processing plant located in western Kentucky. These exposure events demonstrate that air pollution is a health issue everywhere including in Kentuckiana and regionally. We will use Louisville’s particulate air pollution to perform controlled exposures to better understand the ways that air pollution influences cardiovascular health. Ultimately, we want to better protect the health of members of our regional community and worldwide with special emphasis on those who have pre-existing conditions such as high blood pressure – the most important modifiable risk factor of cardiovascular disease in the world.
Interdisciplinary Pilot Project Award:
Principal Investigator: Mikus Abolins-Abols, Ph.D. and Ray Yeager, Ph.D.
Title: "Songbirds as air pollution sentinels for public health: jointly testing the effect of pollution on avian and human stress and inflammation markers"
Description of Project: Exposure to air pollution has well documented negative effect on human health. However, assessing the health risk of air pollution at a local scale can be difficult due to many barriers to localized human studies. Using wild animals as bioindicators of pollution can solve these issues. Birds and mammals respond to pollution in very similar ways to humans, and large numbers of animals can be sampled more rapidly and affordably than humans. In this study, we will ask if American robins, common native urban songbirds, can serve as bioindicators for air pollution by comparing how air pollution affects health of both robins and humans in the same locations. This study has the potential to provide new insights on the burden of pollution exposure on cardiovascular disease across diverse communities in Louisville and other cities across the South and Midwest. This work could ultimately inform novel ways to identify, assess, and develop interventions to environmental health issues.
Interdisciplinary Pilot Project Award:
Principal Investigator: Haixun Guo, Ph.D.
Co-Investigator: Lu Cai, M.D., Ph.D.
Title: "64Cu-PET metallomics for non-invasively tracing copper distribution in response to cadmium and/or HFD"
Description of Project: Cadmium has been known to cause a variety of ill effects from acute and chronic exposure, including nausea, vomiting, diarrhea, muscle cramps, liver injury, convulsions, and kidney failure. Long-term exposure to environmental contaminated metals, such as cadmium in drinking water and food has been linked to health problems such as liver, bone, and blood damage (US. Environmental Protection Agency, 2003). Although cadmium in Kentucky groundwater rarely exceeds the maximum contaminant level (MCL), Kentucky has been ranked number one as cadmium contamination by EPA, due to the coal mine and other industries. For instance, cadmium concentrations might expect to be higher in western Kentucky (specifically Caldwell, Crittenden, and Livingston Counties), where fluorspar was mined in the 1940’s, because of the association of barium and galena (lead ore) with fluorite. The Eastern Kentucky Coal Field also contains high amounts of sphalerite (zinc ore) associated with coal seams, which could cause higher cadmium levels. Therefore, to understand how cadmium affect our body is very important for us to develop the means to prevent cadmium-caused bad effect on our body. It is known that one of the reasons why cadmium exposure damage our body is due to its disturbance of other metals that are need to keep certain level for keeping us healthy. We already know cadmium exposure increases our body copper levels that also cause our tissue cell death. Therefore, we need to know which organ enriches the copper in the body. Therefore, there is an urgent need for tool and technology to non-invasively diagnosis, measure, and monitoring the cadmium exposures across the lifespan for Kentucky residents. The current project utilizes the non-invasive in vivo imaging technology, PET metallomics, to track the dynamic copper homeostasis response to the cadmium exposure in living bodies. The success of this project will provide a non-invasive imaging technology for monitoring the cadmium exposure-altered copper homeostasis in vivo. Such imaging technology can be translated directly to cadmium-exposed patients by using the clinical PET scanner in Radiology for both diagnosis and therapeutic efficacy monitoring.
Interdisciplinary Pilot Project Award:
Principal Investigator: Banrida Wahlang, Ph.D.
Collaborator: Shesh Rai, Ph.D. and Michael Merchant, Ph.D.
Title: "Sex-dependent Effects of Organochlorine Pesticides on Metabolic Diseases: Role of the Gut-Liver Axis"
Description of Project: Organochlorine pesticides (OCPs) were initially manufactured for agriculture and household purposes but were banned worldwide two decades ago when it was discovered that these chemicals elicited harmful effects on our ecosystem and wildlife. Despite this ban, OCPs continue to persist in our environment including our soils and rivers due to their resistance to chemical degradation, which is why OCPs are commonly referred to as “forever chemicals”. Exposures to OCPs still occur throughout the world, and not just in certain developing countries where these chemicals are still in use. The United States, too, has considerable exposure rates even though it was one of the first countries to ban these pesticides. In fact, significant levels of these chemicals were recently detected in residential areas in Louisville, Kentucky. The EPA reported that these detected OCPs likely migrated through the soil and sewer system, from the Black Leaf Chemical plant, which was already abandoned decades ago. The presence of these chemicals in the Ohio River and other Kentucky streams have also been reported. Importantly, marine organisms including fish can accumulate these “forever chemicals” in their bodies, and exposure in humans often occur through ingestion of pesticide-laden fish and water. Indeed, significant levels of these pesticides are still detected in blood samples in the American adult population. Scientific studies have shown that increased levels of these pesticides in human blood are directly correlated with numerous diseases, including obesity, high cholesterol levels and fatty liver. However, studies looking at how these chemicals can contribute to these diseases are still scarce and limited. Moreover, most published studies looking at health effects of pesticides in humans were done in agricultural workers, who were predominantly men. Therefore, this proposal seeks to understand “how” exposure to OCPs can contribute to such liver and metabolic diseases, and if the impact from these exposures is “different between males and females” (sex differences). Identifying how sex differences influence chemical exposure is of utmost importance because it may help explain why some diseases are more prevalent in women, while others are more prevalent in men. Furthermore, men and women may behave differently in their responses to chemical exposure due to their fundamental biological make-up and can have different levels of these chemicals in their bodies. Thus, the proposal, if funded, will provide ground-breaking insight into how pesticide exposure, which is relevant to the Louisville Regional Community, can contribute to metabolic diseases. The information, concepts and findings gained from this proposal will contribute to people in our community in the following ways: this research will 1)will help address sex and gender disparities in environmental health, 2) provide health authorities with further knowledge to identify environmentally-induced diseases in susceptible populations, 3)provide information for policy changes and decision-making, 4) help design sex-specific intervention strategies to better control future health care costs.
Interdisciplinary Pilot Project Award:
Principal Investigator: Barbara Clark, Ph.D. and Carolyn Klinge, Ph.D.
Consultant: Nichola Garbett, Ph.D.
Title: "STARD5 and lipid dysregulation in toxicant-associated steatohepatitis (TASH)"
Description of Project: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder that is characterized by an accumulation of fats in the liver, termed steatosis. NAFLD has increased in parallel with the rise in obesity over the past decade. Simple fatty liver (steatosis) can progress to fatty liver with inflammation (steatohepatitis or NASH). It is well-established that environmental chemicals, or toxicants, worsen obesity-induced NASH and this disease has been defined as toxicant associated steatohepatitis (TASH). Currently, there is no FDA-approved treatment for NAFLD-NASH/TASH, and agents that have shown beneficial results in phase III clinical trials appear to be effective on only a subset of patients. Therefore, there is a need to identify novel markers or druggable targets that may work on a subset of patients not responsive to the current therapies. We have identified a potential novel target, called STARD5, and the goals of this pilot project are to determine whether STARD5 contributes to TASH development. To address this question we generated a mouse that lacks STARD5 (Stard5-/-) and treated them with the endoplasmic reticulum (ER) stress inducer Tunicamycin. Chronic ER stress from over nutrition and environmental toxicants contributes to development of NAFLD/TASH and this pilot project will answer the question if the ER stress-induced liver NAFLD/NASH markers are different between the Stard5-/- and wild-type mice. We have also modeled polychlorinated biphenyls (PCBs), major environmental toxicants of concern, binding to STARD5. This pilot project will determine whether selected PCBs physically bind to STARD5. The potential for a STARD5-PCB interaction could alter the toxicity of PCB exposure in TASH development. Detection of PCBs in human populations is widespread and higher serum PCB levels have been associated with greater liver disease severity. PCB exposure is likely higher for residents surrounding the Arkema facility located in Marshall Co, KY (western KY region) that was a PCB manufacturing facility. The data generated from this pilot project will support future investigations on STARD5 as a risk factor for development of TASH.