TRSC CUSP Awards
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New Hypothesis Expansion/Direction Medium TRSC Research Voucher Award(s): Medium research voucher applications support the expenses (up to $5,000) associated with critical exploratory research and proof-of-concept studies needed by CIEHS members for hypothesis generation and grant (re)submission.
Principal Investigator: Jiapeng Huang, MD, PhD
Collaborators: Lu Cai, MD, PhD and Maiying Kong, PhD
Title: Statistical Analysis of the Pulmonary Arterial Hypertension Biobank Clinical Data and Metallomics
Lay Description: The causes of pulmonary arterial hypertension (PAH) is extremely complex, involving genetic, epigenetic, environmental factors, inflammation, oxidative stress, and metabolic transformation. There is no effective therapy currently. This proposal will comprehensively analyze the clinical data in the PAH Biobank, integrate metallomics data with clinical data, identify significant risk factors for worse PAH clinical outcomes, and design well controlled clinical trials to optimize metal concentrations in PAH.
New Hypothesis Expansion/Direction Medium TRSC Research Voucher Award(s): Medium research voucher applications support the expenses (up to $5,000) associated with critical exploratory research and proof-of-concept studies needed by CIEHS members for hypothesis generation and grant (re)submission.
Principal Investigator:Natalie DuPre, ScD
Collaborator: Lu Cai, MD, PhD and Sandy Kavalukas, M.D.
Title: Biospecimen Processing, Storing and Metal Levels For Epidemiologic Studies Of Cancer
Lay Description: The proposed research is relevant to public health because novel short-term and long-term environmental risk factors may be identified for the development of colorectal cancer, the 3rd most commonly diagnosed cancer in the US. This may explain health disparities due to environmental injustices and/or the rise of early onset colorectal cancer. This study is important because alternative prevention strategies for colorectal cancer could stem from environmental interventions at the individual-level or via public health policy (e.g., promote colorectal cancer screening in communities with high environmental contamination and/or more closely monitor metallic pollutants in residential areas).
New Hypothesis Expansion/Direction Medium IHSFC Research Voucher Award(s):Medium research voucher applications support the expenses (up to $5,000) associated with critical exploratory research and proof-of-concept studies needed by CIEHS members for hypothesis generation and grant (re)submission.
Principal Investigator: Jiapeng Huang, MD, PhD
Collaborator:Lu Cai, MD, PhD; Jun Cai, MD, PhD
Title: Effects And Mechanisms of Antimony During Pulmonary Arterial Hypertension Pathogenesis
Lay Description: The etiology of pulmonary arterial hypertension (PAH) is extremely complex, involving genetic, epigenetic, and environmental factors. We hypothesize that heavy metal, antimony, may directly induce PAH, and would significantly facilitate the development or worsen the pathogenesis of PAH via disturbance of the redox homeostasis. We aim to examine effects of antimony on PAH and right ventricular dysfunction by direct exposure, which will shed light on roles of low dose antimony exposure in PAH pathogenesis and help identify novel therapeutic targets for PAH.
New Hypothesis Expansion/Direction Medium TRSC Research Voucher Award(s): Medium research voucher applications support the expenses (up to $5,000) associated with critical exploratory research and proof-of-concept studies needed by CIEHS members for hypothesis generation and grant (re)submission.
Principal Investigator: Lu Cai, MD, PhD
Collaborators: J. Christopher States. PhD, Ted Smith, PhD, Aruni Bhatnagar, PhD; Emory University Collaborators: Doug Walker, PhD, Dean Jones, PhD
Title: Wastewater Exposome Screening In Jefferson County
Lay Description: Developing approaches to measure the exposome will provide an avenue toward precision environmental health. This project proposes to use analysis of wastewater samples to provide data on chemical exposome across a defined geographic area. The exposome data can be correlated with health data to gain insight into correlations between specific exposures and disease.
New Hypothesis Expansion/Direction Medium TRSC Research Voucher Award(s): Medium research voucher applications support the expenses (up to $5,000) associated with critical exploratory research and proof-of-concept studies needed by CIEHS members for hypothesis generation and grant (re)submission.
Principal Investigator: Venkatakrishna Jala, PhD
Collaborator: Mayukh Banerjee, PhD
Title: Effect of Arsenic Exposure on Intestines
Lay Description: Arsenic exposure causes significant damage to the gastro-intestinal (GI) system. Here, we identified microbial metabolite Urolithin A potentially protect against arsenic induced GI tissue damage. We propose to identify the potential mechanisms by determining the differential gene expression patterns between treatment group versus control group of mice.
Large TRSC Research Voucher Award(s)(up to 25% total costs capped at a $10,000 maximum): Large research voucher applications will be provided to subsidize already funded EHS research (for example NIEHS).
Principal Investigator: Timothy O’Toole, PhD
Collaborator: Lu Cai, MD, PhD
Title: Metalomics of NEAT Cohort Samples
Lay Description: The inhalation of fine airborne particulate matter (PM2.5) is associated with a diverse array of cardiovascular, immunological, and neurocognitive disorders and contributes to increased mortality throughout the world. The Nucleophilic Defense Against PM Toxicity (NEAT) study, is an NIH-supported, double-blinded, clinical trial examining whether dietary supplementation with carnosine can mitigate the adverse effects of PM2.5.More than 250 participants will be enrolled in the NEAT study and randomized to receive placebo or carnosine tablets during the summer months when local PM2.5 levels are at their highest. During these study periods, we will collect blood and urine from study participants for the analysis of biomarkers indicative of pre-clinical vascular disease and will make direct assessments of vascular function, cognition and physical function as well. Funds supplied in this researcher voucher will support the NEAT study overall and will expand upon its goals and impact by allowing the quantitation of 23 metals in collected blood and urine samples. This is a here-to-fore unmeasured endpoint in our study, which may nevertheless be of importance given the role of environmental metals in impacting cardiovascular function, neurodegenerative disease, and frailty. Use of these funds in the NEAT study will enable a more rigorous characterization of local PM2.5 composition, provide insight into the mechanisms of PM2.5 toxicity, and assist in evaluating the potential therapeutic impact of dietary carnosine supplementation.
Small TRSC Research Voucher Award(s): Small research voucher applications (up to $1,500) support the costs associated with research needed to finish out a project or address questions arising in manuscript revisions or grant resubmissions.
Principal Investigator: Timothy O’Toole, PhD
Collaborator: NA
Title: Markers of physical strength and aging in the NEAT cohort
Lay Description: In addition to promoting inflammation and pre-clinical cardiovascular disease, the inhalation of air pollution particles may also contribute to physical frailty and aging, and we are addressing these effects in our current study cohort by measuring hand grip and leg strength. An additional indicator of physical strength that is sometimes used is blood plasma levels of suPAR. Elevated levels of suPAR are associated with an accelerated pace of aging and declines in physical and cognitive function. This award will allow us to measure suPAR in our local study cohort, enabling a rapid assessment of the biological links between air pollution and impaired physical function.
Large TRSC Research Voucher Award(s)(up to 25% total costs capped at a $10,000 maximum): Large research voucher applications will be provided to subsidize already funded EHS research (for example NIEHS).
Principal Investigator: Lonnie Sears, PhD
Collaborator: Kristina Zierold, PhD (UAB), Lu Cai, MD, PhD, Clara Sears, PhD
Title: Metal(loid) body burden in children living near coal power plants
Lay Description: The research voucher will fund ICP-MS to be used to assess finger and toe nails as biomarkers of heavy metal exposure in children living near coal ash storage sites. ICP-MS will provide information on metal body burden in a sample of 260 children and identify metals potentially impacting child neurobehavioral health.
Medium TRSC Research Voucher Award(s): Medium research voucher applications support the expenses (up to $5,000) to cover costs associated with critical exploratory research and proof-of-concept studies needed for hypothesis generation and grant (re-)submission.
Principal Investigator: Timothy O’Toole PhD
Collaborator: NA
Title: The Nucelophilic Defense Against PM Toxicity (NEAT) Trial
Description: Extensive epidemiologic data have indicated that exposure to particulate matter air pollution (PM2.5) is associated with a variety of pulmonary, immunological, cardiovascular, and cognitive disorders. Oxidative stress and inflammation have been implicated as causative agents in PM2.5-induced vascular toxicity and we have previously shown that strategies to limit oxidative stress in mice mitigate these adverse effects. One particularly effective strategy in mice has been dietary supplementation with carnosine, an endogenous dipeptide (b-alanine-L-histidine) found at high levels in the skeletal muscle, brain and heart. Among its chemical properties, carnosine can neutralize unsaturated aldehydes produced as a consequence of oxidative stress. To assess the efficacy of carnosine supplementation in humans, we have devised a double-blind randomized clinical study, the Nucleophilic Defense Against PM Toxicity (NEAT) trial. In this study 240 individuals will be randomly selected to take either carnosine or placebo supplements for 12 weeks over two summer periods (2021 and 2022), when local PM2.5 levels are at their highest. At baseline (prior to taking tablets) and twice during the 12-week supplementation period, we will collect blood and urine from the participants for the measurement of biomarkers, as well as make direct measures of vascular function, cognitive function, and physical strength. Statistical modeling approaches will be used to assess associations between PM2.5 exposure, adverse outcomes, and mitigation by carnosine.
Principal Investigator: Jiapeng Huang, MD, PhD
Collaborator: Lu Cai, MD, PhD
Title: The Impact of Cadmium on Pulmonary Arterial Hypertension in a Mouse Model
Description: This project will explore whether exposure to cadmium may worsen pulmonary hypertension and right ventricular dysfunction in a mouse model. The results will shed lights on environmental effects in the etiology and progression of pulmonary hypertension and right ventricular dysfunction.
Medium TRSC Research Voucher Award(s): Medium research voucher applications support the expenses (up to $5,000) to cover costs associated with critical exploratory research and proof-of-concept studies needed for hypothesis generation and grant (re-)submission.
Principal Investigator: Loretta Jophlin, MD, PhD
Collaborator: Matt Cave, MD
Title: Mechanisms of hepatic stellate cell activation and liver fibrosis in toxicant associated steatohepatitis.
Description: A comprehensive understanding of the mechanisms regulating fibrosis in toxicant associated steatohepatitis (TASH) is critical for the development of therapeutics aimed at treating the clinically significant endpoints of TASH, e.g. advanced hepatic fibrosis and cirrhosis. This TRSC Research Voucher will allow for exploratory translational research and proof-of-concept studies aimed at obtaining pilot funds and the eventual submission of an NIEHS R01 grant focused on druggable anti-fibrotic targets in patients with TASH.