Lay Summaries of Funded Pilot Projects
2024
PROJECT TITLE: Investigating The Role of Volatile Organic Compounds in Breast Cancer Risk and Progression
PI: Sue Fenton, Dept. Biological Sciences, NC State University
In recent decades, breast cancer incidence in young (premenopausal) women and men has risen at a slow, but steady pace. Environmental exposures to man-made chemicals are thought to contribute to that rise. Volatile Organic Compounds (VOCs) are a mixture of chemicals that have been associated with breast cancer in men and women who served as a Marine or lived in Camp Lejeune, NC. To test if VOCs affected mammary tumor risk, pregnant rats were exposed to a VOC mixture mirroring that at Camp Lejeune and mammary tumors were noted in male and female offspring. Using stored samples from that study we propose to evaluate differentially expressed genes in tumors and normal mammary tissue induced by VOCs to better understand mechanisms surrounding these effects. We will also use human breast cancer diagnostic markers (currently used in clinics for precision treatment options) to compare to both the rat genomic dataset and sectioned rat tumors stained with breast tumor subtype antibodies (ER, PR, Her-2/neu, and Cytokeratin5) to enhance translation of outcomes in rat and human tumor studies in the future.
PROJECT TITLE: Investigating the link between atrazine and intestinal birth defects
PI: Nanette Nascone-Yoder, Department of Molecular Biomedical Sciences, NC State University
Atrazine (ATR) is the second most common herbicide in the US and is frequently reported above the regulatory limit in potable water supplies. A known endocrine- and metabolism-disrupting compound, ATR also affects animal cells and has been associated with adverse pregnancy outcomes and birth defects in humans. Our previous studies in frog embryos showed that ATR elicits intestinal malrotation, a life-threatening malpositioning and twisting of the intestine tube that occurs in 1 in 500 births. The underlying causes of this common birth defect are poorly understood. We recently discovered that the left versus right sides of the frog intestine elongate at different rates; this inherent asymmetry causes the intestine to curve and rotate as it lengthens. If ATR affects this novel developmental process, that could explain how it causes intestinal malrotation. In this project, we will determine the effect of ATR exposure on the left versus right cell properties and patterns of gene activity that drive left-right asymmetric intestine elongation. As similar cellular and molecular processes are used in the development of other organs, understanding how ATR exposure affects intestinal elongation and rotation in frogs has implications for how similar toxins, or mixtures of toxins, may cause multipledevelopmental defects across species, including humans.
Project Title: Investigating how exposure to the toxic metal cadmium in early life affects liver health and aging
PI: Michael Cowley, Dept. Biological Sciences, NC State University
Background: Cadmium is one of the top ten chemicals of major public health concern identified by the World Health Organization. Humans can be exposed to cadmium through tobacco smoking, eating contaminated food, or drinking contaminated water. Some pregnant women show high levels of cadmium in their blood, suggesting that children could be exposed before birth or while breastfeeding. Our prior work has focused on understanding how exposure to cadmium during this window affects the developing liver, leading us to propose that cadmium causes the liver to undergo accelerated aging, making it vulnerable to other stressors and increasing disease risk.
Methods: The proposed study will test the idea that early life cadmium exposure causes accelerated aging of the liver using cultured cells and mice. We cannot study human subjects because of ethical reasons, but we will continue our long-standing collaborations with Dr Cathrine Hoyo (epidemiologist, NC State) and Dr Anna Mae Diehl (hepatologist, Duke University) to ensure that our findings are relevant to humans.
Importance and implications: Cadmium poses a public health problem, including for children. If our hypothesis is correct, our work will represent a substantial step forward in understanding how cadmium causes disease, opening the doors to developing approaches that might protect children from the impacts of exposure. Our findings will advance the field by identifying novel mechanisms linking early life exposure to aging, a critical area that is under-explored.
Project Title: Human pollutants in African rivers important for protecting human health and
biodiversity – methods development for study of wildlife and human exposures
PI: Scott Belcher, Dept. Biological Sciences, NC State University
Background: The World Health Organization (WHO) found that at least 2.2 billion people live without safe drinking water. Low- and middle-income countries are disproportionally impacted and there is a critical need to understand the types of pollutants that are impacting humans and critical economic resources such as wildlife. The proposed studies will develop methods to evaluate the chemical pollutants present in endangered wildlife on protected lands being impacted by human waste and pollution in South Africa.
Methods: The pilot funding requested here will be used to support travel, sample collection, andoptimization of analysis of biological samples by the Belcher lab. Non-invasive field samples (feces) from animals in protected areas will be led by Dr. Webster with trained trackers from the community. The Belcher lab will collaboratively collect and return samples to NC State where sample preparation, extraction, and MS analysis of PFAS and metals from each type of sample will be optimized. The method development is critical for demonstrating analysis feasibility for the many different types of samples and will be key preliminary data necessary for competitive grant funding.
Importance/Implications: The key importance for CHHE is to acquire preliminary results to support international funding (e.g. Belmont Foundation, WHO, NIEHS) for research on mitigating environmental and human health impacts of human derived chemicals and waste during a time of changing climate and extreme weather events.
Project Title: Do Forever Chemicals Influence Eye Health?
PIs: Tracey Woodlief & Jessica Bailey, Dept. of Pharmacology & Toxicology, ECU
Background Info: Per- and polyfluoroalkyl substances (PFAS), often called “forever chemicals,” are present in common items such as food packaging, non-stick pans, and waterproof clothing. Research indicates that PFAS exposure can lead to severe health issues, including cancer, liver damage, and high cholesterol. Low-income communities face higher exposure rates and an increased burden of health disparities. However, the full impact of PFAS on human health, particularly eye health, remains unclear. This project aims to explore how PFAS exposure affects eye health.
Methods: In Specific Aim 1, Dr. Woodlief will administer PFOA or PFOS to mice over a 30-day period. Post-exposure, ocular tissues will be analyzed for PFAS concentrations, serum inflammatory markers, and molecular changes associated with eye disease to reveal PFAS-related mechanisms of eye disorders. In Specific Aim 2, Dr. Cooke Bailey will evaluate PFAS levels and inflammatory biomarkers in blood samples from patients with and without glaucoma, drawn from both urban and rural areas. This aim is to address the knowledge gap on how environmental contaminants contribute to health disparities, especially among historically marginalized populations.
Importance and Implications: This study is crucial for understanding how PFAS may impact vision and eye health. By revealing the links between environmental exposures and eye problems, the findings will guide strategies to protect vulnerable groups, improve health outcomes, and reduce health inequalities.