Please describe the research questions of your lab.
I am currently a senior postdoctoral researcher in the Chris Carlsten lab at the University of British Columbia (UBC). Our lab investigates the effects of environmental exposures on the lungs, with a focus on diesel exhaust as a model of traffic-related air pollution (TRAP) exposure in asthma and COPD. We are interested in understanding the effects of diesel exhaust exposure at a mechanistic level and how responses are affected by factors, such as time, concentration, co-exposure to allergens, antioxidant supplementation or treatment with corticosteroids. My research has to date focused on the analysis of microRNA, messenger RNA and DNA methylation in these study samples.
I also have a keen interest in how responses to glucocorticoids are modified by inflammatory factors, including air pollution exposure. I recently authored a review discussing the modest evidence that air pollution exposure induces glucocorticoid resistance. We are starting a controlled human exposure study to investigate the effects of inhaled budesonide on acute exposure to diesel exhaust which will allow me to integrate these two major areas of interest. Our hope is that our research will contribute to the refinement of environmental policy and improved treatment of important lung diseases.
What genetics/genomics techniques do you utilize in your lab?
Because of the difficulty of performing controlled human exposure studies the data that we obtain are precious, and we therefore attempt to obtain as much information as possible from these samples. We do a lot of in-house analysis of blood and BAL samples using flow cytometry and microscopy. We also collaborate with Dr. Michael Kobor (UBC) on DNA methylation analysis and Dr. Neeloffer Mookherjee (University of Manitoba) on proteomics. Additionally, we employ a range of non-genomics techniques from questionnaires through spirometry to complete blood counts. We are increasingly using bioinformatics and statistical techniques to integrate the different layers of our data with the hope of obtaining an improved understanding of the effects of exposures.
Describe a key technique/assay/instrument utilized in your lab, and what novel insights does it bring to your research question?
The DNA methylation data obtained from our controlled human exposure studies have yielded a number of novel insights so far, but we are still in the early stages of integrative analysis. Our data indicate that exposure to diesel exhaust and allergen results in changes to DNA methylation in the blood that increase up to 48 hours. We also have data that suggests that DNA methylation of bronchial epithelial cells is altered by diesel exhaust and allergen exposure and that priming effects of exposure may be sustained over time. These results may help explain how exposure to TRAP and allergens contributes to asthma development.
At what point in your life did you decide you wanted to be a scientist/physician?
I think I first started to seriously consider becoming a researcher in high school in about 1998, after reading a number of books on genetics, including Richard Dawkins' the selfish gene, Steve Jones' the language of genes and Matt Ridley's the origins of virtue. I had an interest in this area earlier as remember begging my parents for various science sets and a microscope. I chose to focus on respiratory diseases as both my mother and sister have asthma and so completed a PhD in respiratory sciences in the Newton lab at the University of Calgary.
In your opinion, what is one of the most important discoveries in the field of respiratory illness/disease/function that was dependent on genomics or similar techniques?
I think the increasing computational power delineated by Moore's law has been of substantial benefit to all areas of research, including in respiratory diseases. Increasingly this is allowing us to perform more complex multi-omics analyses. This, alongside the swift drop in the price of sequencing, has opened up a whole new vista in areas, including thoracic oncology. The recent development of single-cell RNA-seq has started to enhance respiratory research through our improved understanding of the many cell types present in the lungs and their differing gene expression profiles. Additionally, improved understanding of mutations in cystic fibrosis transmembrane conductance regulator and development of therapy was a milestone. I believe we are only starting to appreciate the benefits of improved understanding of DNA methylation and epigenetics in general. I believe one fascinating area of future research will be the effects of lung diseases, such as COPD, on the epigenetic clock/DNA methylation age acceleration and the implications this has for treatment and predicting mortality.
Briefly describe your favorite publication involving genomics/omics that you were involved with (with a PMID or reference) in general-audience terms.
While my favourite paper is always the one that I will publish next, one memorable paper was "Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers" (PMID: 27283384). This paper investigated the effects of exposure to an allergen, diesel exhaust or the combination on microRNA, gene expression and inflammatory markers in the lung.
We found that allergen exposure evoked significant changes in gene and miRNA profiles, while, in contrast, the effects of diesel exhaust were more limited. At this late time point in our stringent models, we did not find that diesel exhaust and allergen exposure interacted in affecting miRNA or gene expression. These results suggest that adjuvant effects of diesel exhaust on these endpoints may be transient or require higher or prolonged exposure, but that allergen and diesel exhaust exposure nevertheless modulated factors important in asthma at this late time point.
What is your favorite aspect of ATS?
I really enjoy many aspects of the ATS including having my eyes opened to new research, meeting collaborators and developing connections with other basic and clinical investigators. I particularly enjoy being able to put faces to the author lists of interesting papers I have read. One aspect of the ATS that has been especially helpful is the mentorship program, in which junior trainees like me are matched with well-established researchers. This enabled me to meet and get outstanding careers advice from talented individuals, including GG members Dr. Oliver Eickelberg and Tricia LeVan.
How could your research assist scientists and clinicians in other assemblies at ATS?
My research is relevant to the mandates of other assemblies, particularly the environmental, occupational and public health (EOPH) assembly. I am also a member of the respiratory cell and molecular biology (RCMB) assembly, due to my interests in the effects of glucocorticoids in bronchial epithelial cells. We have access to unique human data and banked samples that we can share with collaborators potentially boosting the impact of publications.
Would you be open to collaborations with GG and/or non-GG scientists and clinicians?
Both Dr. Carlsten and I are always interested in collaborations that can enhance respiratory research. Just reach out to us if you have an exciting project idea.
Do you have any potential lab openings currently or in the near future?
The Carlsten lab does not have any specific openings currently, but we always welcome applications from talented undergraduates, graduate students, postdocs and those who wish to join us as visiting scientists.
Lab website address and email address:
Our lab website is www.pollutionlab.com, and you can contact me at c.rider@ubc.ca . You can also email Dr. Carlsten directly at carlsten@mail.ubc.ca.