(337cb) A Systems Biology Approach to Understanding Environmental Stress Responses in Human Lung Cells

Exposure to air pollution is linked to diseases of the lungs, brain, and heart and is estimated to contribute to over 7 million deaths annually by the World Health Organization. Although the link between exposure and adverse health effects has been made apparent through epidemiological studies, the role of unique air pollution components in disease pathogenesis needs to be further characterized on the cellular and molecular level. It has recently become apparent that RNA modifications, or the epitranscriptome, have important regulatory roles in many cellular functions, including stress responses. In this study, we couple quantitative transcriptomics and epitranscriptomics with single-cell morphological analysis to better understand the effects of environmental toxins on human lung cells.

Specifically, we examine human bronchial epithelial cells (BEAS-2B cells) as a model system to determine the effects of airborne particulate matter (PM) mixtures. We use an interdisciplinary approach involving RNA sequencing and large-scale epitranscriptomics to map specific RNA modifications across the transcriptome coupled with quantitative analyses of changes in cellular morphological traits. Using these systems and quantitative biology tools, we have developed an integrated approach that combines large-scale biological data to understand the interplay between environmentally-induced transcriptional changes and the resulting changes to the epitranscriptome. Collectively, these methods have allowed us to show broad changes in the levels of RNA modifications can be induced by particulate matter stress. We have also used this approach to show that the epitranscriptome provides an additional method of regulation used to respond to environmental stress by altering patterns of RNA modifications on key RNA transcripts involved in the stress response. Additionally, these changes in transcriptomic regulation result in unique morphological readouts in cells. Together, this systematic approach helps to deconvolute how the epitranscriptomic regulation contributes to lung cell health. We believe this approach can be broadly applicable to investigate subtle changes in cellular responses to different stimuli and pathologies.

Research Interests

I am interested in utilizing large-scale datasets to answer elusive biological questions relating to cellular stress responses, pathologies, and therapies. I am particularly interested in deciphering the role that the epitransriptome, or RNA modifications, play in different biological contexts. This layer of control over gene expression is just beginning to be understood and impacts functions of not only protein-coding mRNAs, but also regulatory non-coding RNAs, interactions with proteins, and has been implicated in the development of many human pathologies including cancers. Understanding these RNA modifications and their governing protein-based regulation could allow for development of new biomolecular tools and therapeutic approaches to treat the pathologies associated with altered RNA modification patterns.