Collaborative Applied Statistics

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As an interdisciplinary scientist, I work with a number of collaborators both within and outside the NIEHS and applied studies. Such collaborations provide the opportunity to be involved in high impact science, and to realize important gaps in current methods that inspire methods development work. In a continuing collaboration with Dr. Matthew Breen at NCSU, we have completed several studies in this last year related to understanding the genetic and environmental factors that underlie the etiology of cancer in canines as a model for better understanding cancer in humans. A lack of understanding regarding the mechanisms of disease development and progression hinders development of novel therapeutics. Our study aimed to improve the understanding of underlying disease mechanisms using genome-wide DNA copy number and gene expression analysis of spontaneous HM across several dog breeds. Copy Droplet digital PCR evaluation of the regions in numerous cancer specimens effectively discriminated HM from other common round cell tumors resulting in a novel, rapid diagnostic aid for veterinary medicine. Silicone wristbands are promising passive samplers in characterizing exposure to organic contaminants; however, investigating associated health risks remains challenging because of the latency period for many chronic diseases that take years to manifest. In another collaboration with Dr. Breen, we evaluated exposures among pet dogs and their owners using silicone dog tags and wristbands to demonstrate that contaminant levels were correlated with validated exposure biomarkers and demonstrated strong correlations. This supports the value of using silicone bands with dogs to investigate health impacts on humans from shared exposures. I also worked with another collaborator using the canine model - Dr. Lauren Trepanier at the University of Wisconsin. Non-Hodgkin lymphoma in humans is associated with environmental chemical exposures, and risk is enhanced by genetic variants in glutathione S-transferases enzymes. We resequenced variant loci in canine GSTT1, GSTT5, GSTM1, and GSTP1 and compared endogenous DNA damage in peripheral leukocytes of boxers and nonboxers using the comet assay. We also compared GST variants and questionnaire-based environmental exposures in boxers with and without lymphoma. Proximity to nuclear power plants, chemical suppliers, and crematoria were significant risk factors for lymphoma in this population of boxers. Additionally, I collaborated with Dr. Stephanie London here at NIEHS. We conducted the largest epigenome-wide association study of blood DNA methylation in adults in relation to non-atopic and atopic asthma. Participants were categorized as atopy without asthma , non-atopic asthma , atopic asthma , or a reference group of neither atopy nor asthma. Numerous CpGs were differentially methylated in non-atopic asthma and implicated 382 novel genes. More CpGs were identified in atopic asthma and implicated 569 novel genes. I have also continued collaborative work in metabolomics, with Dr. Rima Kaddurah-Daouk. Alzheimer's disease is the most common cause of dementia. The mechanism of disease development and progression is not well understood, but increasing evidence suggests multifactorial etiology, with a number of genetic, environmental, and aging-related factors. To interrogate the relationship between metabolites and disease susceptibility and progression, we worked with the AD Metabolomics Consortium and AD Neuroimaging Initiative. We used the Biocrates Bile Acids platform to evaluate the association of metabolic levels with disease. A second study with her in metabolomics evaluated metabolomics with food allergy. We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA. In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. We demonstrated that children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. I also have been collaborating with Drs. Janet Hall, David Fargo, Charles Schmitt, Miller and Akhtari on statistical genetics in the Environmental Polymorphisms Registry. We are working on several projects including exposome-wide association studies of both immune mediated disease and cardiovascular disease. I have recently recruited a new post doc fellow, Dr. Eunice Lee to work on these projects. We are currently processing and cleaning the whole genome sequencing data.