FIRG pilot projects

To foster the growth of cutting-edge interdisciplinary research, CEHS began providing funding for pilot projects that target new ideas from the Flexible Interdisciplinary Research Groups (FIRGs). Center researchers, along with scientists in other University departments, have been awarded three $50,000 grants to explore innovative environmental health research that can reduce the burden of disease. The FIRG pilot projects are funded through the NIEHS-approved Center Director Funds.

 Previously awarded FIRG Pilot Projects


The following proposal for FIRGs was approved for funding in 2012:
 
Project: Inorganic arsenic-induced DNA methylation and risk of urinary bladder cancer
PI: Rebecca Fry, PhD, Assistant Professor, Department of Environmental Sciences and Engineering, and Miroslav Styblo, Associate Professor, Department of Nutrition, Adjunct Associate Professor, Department of Environmental Sciences and Engineering
 

Abstract

Cancer of the urinary bladder is one of the most common forms of cancer associated with chronic exposures to inorganic arsenic (iAs). A mechanism for this association is not clearly established and has historically been hindered by a limited access to relevant target tissues for study. This project builds off of existing research in Mexico and enables analysis of target tissues (exfoliated urinary bladder cells) collected in an iAs-exposed population. In preliminary data, we have identified 17 tumor suppressors that are hypermethylated in peripheral blood lymphocyte DNA from iAs-exposed individuals who were diagnosed with precancerous skin lesions. Of note, one of these novel sites miR126, has been shown independently to be silenced in bladder tumors. Importantly, these sites, if similarly altered in bladder epithelial cells, could represent a hitherto unknown mechanism by which iAs induces its effects in the bladder. In this application, the team of FIRG researchers come together to test a common hypothesis related to iAs exposure. Specifically, we hypothesize that iAs exposure alters DNA methylation of tumor suppressors in bladder epithelial cells in a manner that is consistent with DNA methylation in bladder cancer. We are uniquely positioned to test this hypothesis in a cohort of iAs-exposed individuals in Mexico. These study subjects have been well-characterized for their iAs exposures, for inter-individual differences in iAs metabolism, and genetic polymorphisms affecting iAs metabolism and toxicity. In addition, bladder epithelial cells are currently being collected from this population for arsenic analysis. The DNA from these cells will be used in our project to identify the sites of DNA methylation across the epigenome that are associated with iAs exposure. DNA from bladder tumor specimens from clinical samples already collected by our collaborators at the UNC Lineberger Cancer Center will be used as a positive control. This interdisciplinary research is likely to provide new insights into the molecular mechanism of bladder carcinogenesis associated with exposure to iAs and to establish early epigenetic markers for risk assessment of this exposure.

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The following proposals for FIRGs were approved for funding in 2011:

Project 1: Pilot study on mechanisms of soot inhalation injury to large airways in humans.
PI: Terry L. Noah, MD, Professor, Pediatric Pulmonology, and Samuel Jones, MD (Co-PI), Assistant Professor, Surgery; Department of Pediatrics and Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine.
 
PI: Stephanie M. Engel, PhD, Associate Professor, Department of Epidemiology, School of Public Health.

Project 1-2011:

FIRG: Airway Biology and Disease

Project: Pilot study on mechanisms of soot inhalation injury to large airways in humans.
Principal Investigator: Terry L. Noah, MD, Professor, Pediatric Pulmonology, and Samuel Jones, MD (Co-PI), Assistant Professor, Surgery; Department of Pediatrics and Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine.
Award: $50,000

Abstract

Acute lung injury (ALI) after burn/inhalational injuries is caused by environmental factors including smoke, thermal, or chemical injury. Few studies have investigated factors leading to ALI after these exposures. We propose to test the hypothesis that injury responses (inflammatory, antioxidant, antimicrobial) in large airways epithelium, induced by toxins in inhaled soot, contribute to progression to ALI. Our specific aims are to (1) characterize the chemical composition of inhaled soot particles taken directly from the airways of inhalation injury victims; (2) measure the impact of soot particles on cultured human airway epithelial injury response pathways in vitro; and (3) compare levels of injury response factors in bronchial washings between patients who do vs. do not progress to ALI. This project will expand the Pulmonary Disease/CEMALB FIRG to include investigators from the UNC School of Public Health and the NC Jaycee Burn Center, and will provide preliminary data for an extramural grant application aimed at discovering key pathophysiologic pathways and novel therapeutic targets in acute severe environmental toxin inhalation injuries. The project will utilize the CEHS Biostatistics and Bioinformatics, Integrative Health Sciences, and Career Development Cores.

Project 2-2011:

FIRG: Reproductive and Developmental Health

Project: Investigation of biospecimen integrity for the examination of prenatal toxicant exposure in relation to attention-deficit hyperactivity disorder in the Norwegian mother and child birth cohort (MoBa).
Principal Investigator: Stephanie M. Engel, PhD, Associate Professor, Department of Epidemiology, School of Public Health.
Award: $50,000

Abstract

Organophosphate pesticides, bisphenol A (BPA) and phthalates have been implicated in the etiology of Attention-Deficit Hyperactivity Disorder (ADHD), but there have been no prospective studies of prenatal exposure in relation to a clinically defined phenotype. We propose to investigate these relationships in the ADHD substudy of the Norwegian Mother and Child Birth Cohort. This pilot application seeks support for preliminary studies of the suitability of stored biospecimens within the MoBa biorepository to investigate our aims. We propose to conduct a reliability study of free and conjugated BPA over the course of pregnancy using stored MoBa urine samples; to examine the consequences of MoBa maternal plasma shipping in storage methods on FT4 concentration using a small population of women enrolled at UNC; and to investigate the feasibility of extracting FT4 from fetal blood spots. To achieve our aims we will be collaborating with the UNC-CEHS Biostatistics and Integrative Health Sciences and Facilities Cores. This application represents a transdisciplinary collaboration between behavioral scientists, epidemiologists, and clinical investigators, and addresses the complex interaction between environmental exposures and human neurodevelopment.
 
Funded by NIEHS Grant # P30 ES010126