Matthew Jones, PhD
Assistant Professor of Medicine – The Pulmonary Center
PhD: Boston University School of Medicine, PhD, 2003, (Katya Ravid)
Postdoctoral Education: Harvard School of Public Health (Joseph Mizgerd)
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) and microRNA target sequences that can lead to their abrogated translation, deadenylation, and decay. 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.
- Jones MR, Blahna MT, Kozlowski E, Matsuura KY, Ferrari JD, Morris SA, Powers JT, Daley GQ, Quinton LJ, Mizgerd JP. 2012. Zcchc11 uridylates mature miRNAs to enhance neonatal IGF-1 expression, growth, and survival. PLOS Genet 8(11): e1003105.
- Quinton LJ, MT Blahna, MR. Jones, E Allen, JD Ferrari, KL Hilliard, X Zhang, V Sabharwal, H Algül, S Akira, RM Schmid, SI Pelton, A Spira, JP Mizgerd. 2012. Hepatocyte-specific mutation of both NF-kappaB RelA and STAT3 abrogates the acute phase response in mice. J Clin Invest 122:1758-1763.
- Blahna MT, Jones MR, Quinton LJ, Matsuura KY, Mizgerd JP. 2011. Terminal uridyltransferase enzyme Zcchc11 promotes cell proliferation independent of its uridyltransferase activity. J Biol Chem 286:42381-42389.
- Jones MR, Quinton LJ, Blahna MT, Neilson JR, Fu S, Ivanov AR, Wolf DA, Mizgerd JP. 2009. Zcchc11-dependent uridylation of microRNA directs cytokine expression. Nature Cell Biol. 11:1157-1163.