Rachel Fearns, Ph.D.
Professor of Microbiology
Director of Graduate Studies, Microbiology Program
National Emerging Infectious Diseases Laboratories
650 Albany Street, Boston MA 02118
Office: NEIDL 501T; 617-358-9287
Lab: NEIDL 502; 617-358-9195
B.S. University of Leeds
Ph.D. University of St. Andrews
My group’s research focuses on the transcriptional and genome replication mechanisms of non-segmented negative strand RNA viruses. This group of viruses includes a number of significant human pathogens, including respiratory syncytial virus (RSV), human metapneumovirus (HMPV), measles, mumps and parainfluenza viruses, and emerging highly pathogenic viruses, such as Nipah, Marburg and Ebola viruses. Our overarching goal is to understand the processes of transcription and genome replication, both at a molecular level and within the context of the cellular environment. We are accomplishing this by applying biochemistry and molecular biology approaches and by collaborating with researchers with expertise in structural biology and cutting edge cell imaging techniques. By studying representative viruses from three different non-segmented negative strand RNA virus families, we are characterizing the similarities and differences between these viruses. This could help identify suitable targets for development of broad spectrum antivirals and helps us to appreciate the rich diversity of the non-segmented negative strand RNA viruses and the mechanisms that they have evolved to express and replicate their genomes.
Research in the lab can be divided into the following areas:
- Determining the mechanisms by which viral transcription and replication occur and are regulated over the course of infection.
- Deciphering structure-function relationships of the viral polymerase and associated proteins.
- Determining the mechanism of action of small molecule inhibitors of the viral polymerase.
- Pan J, Qian X, Lattmann S, El Sahili A, Yeo TH, Jia H, Cressey T, Ludeke B, Noton S, Kalocsay M, Fearns R, Lescar J. Structure of the human metapneumovirus polymerase phosphoprotein complex. Nature 2020, 577: 275-279. PMCID: PMC6949429.
- Cressey TN, Noton SL, Nagendra K, Braun MR, Fearns R. Mechanism for de novo initiation at two sites in the respiratory syncytial virus promoter. Nucleic Acids Res. 2018. 46: 6785-6796. PMCID: PMC6061868.
- Noton SL, Tremaglio SZ, Fearns R. Killing two birds with one stone: How the respiratory syncytial virus polymerase initiates transcription and replication. PLoS Pathog. 2019. 15:e1007548. PMCID: PMC6394897.
- Braun MR, Deflubé LR, Noton SL, Mawhorter ME, Tremaglio CZ, Fearns R. RNA elongation by respiratory syncytial virus polymerase is calibrated by conserved region V. PLoS Pathog. 2017. 13: e1006803. PMCID: PMC5760109.
- Warren TK et al, Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016. 531:381-5. PMCID: PMC 5551389.
- Noton SL, Nagendra K, Dunn EF, Mawhorter ME, Yu Q, Fearns R. Respiratory syncytial virus inhibitor AZ-27 differentially inhibits different polymerase activities at the promoter. J. Virol. 2015. 89: 7786-7798. PMCID: PMC4505683
- Tremaglio CZ, Noton SL, Deflube LR, Fearns R. 2013. The respiratory syncytial virus polymerase can initiate transcription from position 3 of the leader promoter. J. Virol. 87:3196-3207. PMCID: PMC3592119
- Noton SL, Deflubé LR, Tremaglio CZ, Fearns R. 2012. The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter. PLoS Pathogens 8: e1002980. PMCID: PMC3475672
- C.R. Zack, D.R. McGivern and R. Fearns. 2010. Evidence that the polymerase of respiratory syncytial virus initiates RNA replication in a non-templated fashion. Proc. Natl. Acad. Sci. USA 197:10226-10231. PMCID: PMC2890450
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