Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
microRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression through post-transcriptional targeting of messenger RNAs (mRNAs). Discovered in mammals in 2001, miRNAs have since become appreciated as both biomarkers and drivers of disease, including metabolic diseases such as type 2 diabetes. Metabolic diseases are characterized by systemic energy imbalance, which involve diverse tissues such as liver, pancreas, adipose, brain, muscle, and intestine. Understanding the role of miRNAs in the regulation of these organ systems during normal physiology and disease pathogenesis is a necessary step to help develop effective miRNA-based therapeutics. Toward this goal, in my dissertation research I identify miRNAs that act as biomarkers of metabolic and gastrointestinal (GI) diseases and evaluate their role in gene regulatory networks in the liver and small intestine. miRNAs are severely understudied in the intestine compared to most other metabolic tissues, and specifically in the intestinal epithelium, so I extended my research objective to help bridge this gap by identifying diet- and microbiota-sensitive miRNAs in distinct cell populations of the intestinal epithelium. I found that intestinal epithelial stem cells (IESCs) respond most robustly to these environmental stimuli. Furthermore, I demonstrated that specific microbiota-sensitive miRNAs regulate IESC proliferation, which is a key process underlying intestinal homeostasis. The findings of my research represent key advances in the GI field, and serve as a strong foundation for future research into the role of miRNAs in metabolic and GI disease.