Matthew Jones, Ph.D.
Associate Professor of Medicine
Graduate Education: Boston University School of Medicine, PhD, 2003, Vascular biology
Other Post-doctoral Fellowship: Harvard School of Public Health (Joseph Mizgerd)
- Post-transcriptional gene regulation
- Innate immunity in the lungs
Our research is broadly focused on the host inflammatory response to acute bacterial pneumonia. During pneumonia, various pro-inflammatory cytokines and chemokines are released to guide immune cells to the site of infection. Too much inflammation can compromise normal lung function whereas, too little of a host response can lead to uncontrolled bacterial growth and sepsis. Cytokine expression thus needs to be carefully directed by molecular mechanisms regulating transcription, mRNA stability, and translation. Our work is centered on several aspects of cytokine mRNA instability. In general, cytokine transcripts are very labile which is a property imparted by various sequence elements residing in their 3´ untranslated regions (UTRs). These 3´ UTRs contain AU-rich elements (AREs) that are bound by ARE-binding proteins and direct mRNA translational efficiency and decay. One project in the lab is centered on how specific ARE-binding proteins regulate select cytokine expression during inflammation. In addition to AREs, many cytokine transcript 3´ UTRs are targeted by microRNAs, which can lead to their abrogated translation, deadenylation, and ultimately, decay. Another research focus of ours is exploring how cytokine transcript targeting microRNAs themselves are processed and regulated. We have found that the Zcchc11 protein is a uridyltransferase that is responsible for the uridylation of specific microRNAs. End modifications of microRNAs, such as untemplated uridylation, can reduce their ability to repress the targeted transcript. Future studies are designed to elucidate which microRNAs are modified by Zcchc11 during inflammation and whether these edits have functional consequences. Understanding how these mechanisms function to orchestrate inflammation during pneumonia will provide an important basis for future disease management.
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