Our lab studies the biochemical mechanisms of host-virus interactions, identifying and developing small molecules with antiviral properties and through understanding and harnessing non-coding RNAs as signal transducers and thus important drug targets. Through our research, we have pioneered the development of antiviral strategies based on non-coding RNAs called microRNAs (miRNAs). We have developed novel screening methods, such as ‘small molecule-based annotation of miRNA targets’ that has been used to discover novel microRNAs with biological function (Nature Chem. Biol, 2015). Resulting miRNAs are then studied with a variety of biochemical techniques to uncover the biological mechanisms of their function. Our lab also works on innovative approaches to deliver therapeutic small RNAs, addressing a key medicinal chemistry challenge in the field (Bioconj. Chem. 2019, Mol. Ther. Nucleic Acids, 2016). For example, our group discovered the role that the virus-induced microRNA-27 plays in triglyceride accumulation and liver disease, which led to a cover article in Hepatology (2014) and was highlighted by Genetic Engineering & Biotechnology News and the College of American Pathologists. We also discovered that miRNAs regulate the immunometabolic response to viral infection, work that was highlighted as a top advance in virus research in 2015 by Nature Reviews Gastroenterology and Hepatology.  Our group also identified microRNA-7 as a mediator of cross-talk between metabolic signaling pathways in the liver (Scientific Reports, 2017) and microRNA-124 that was shown to regulate catabolism (iScience, 2018). Our group also discovered a cluster of miRNAs that are immunomodulatory, which resulted in a patented strategy for combating multiple types of viral infection by targeting this miRNA cluster (2018 patent, JBC, 2019). Together, our work is advancing the understanding of non-coding RNAs and has allowed us to target microRNAs for therapeutic development.

Select reviews: 

Powdrill MH, Desrochers GF, Singaravelu R, Pezacki JP “The role of microRNAs in metabolic interactions between viruses and their hosts” Curr. Opin. Virol. 2016, 19, 71-76.  (invited review)

Singaravelu R, Russell RS, Tyrrell DL, Pezacki JP “Hepatitis C virus and human microRNAs: miRed in a host of possibilities” Curr. Opin. Virol. 2014, 7, 1-10.
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Select research articles: 

Evers, P.; Pezacki, J. P. "Unraveling Complex MicroRNA Signaling Pathways with Activity‐Based Protein Profiling to Guide Therapeutic Discovery" Isr. J. Chem. 2023, 63, 3-4, e202200088. DOI: 10.1002/ijch.202200088​

Desrochers, G. F.; Filip, R.; Bastianelli, M.; Stern, T.; Pezacki, J. P. "microRNA-27b regulates hepatic lipase enzyme LIPC and reduces triglyceride degradation during hepatitis C virus infection" J. Biol. Chem. 2022, 298, 6, 101983. DOI: 10.1016/j.jbc.2022.101983

Singaravelu, R., Ahmed, N., Quan, C., Srinivasan, P., Ablenas, C.J., Roy, D.G., Pezacki, J.P. “Conserved miRNA-183 cluster regulates the innate antiviral response”  J. Biol. Chem. 2019, 294, 19785–19794

Shaw TA, Singaravelu R, Powdrill MH, Nhan J, Ahmed N, Özcelik D,  Pezacki JP "MicroRNA-124 regulates fatty acid and triglyceride homeostasis" iScience. 2018,  10, 149-157

Singaravelu R, Quan C, Powdrill MH, Shaw TA, Srinivasan P, Lyn RK, Alonzi RC, Jones DM, Filip R, Russell RS, Pezacki JP "MicroRNA-7 mediates cross-talk between metabolic signaling pathways in the liver" Sci. Rep. 2018,  8:361 

Singaravelu R, O'Hara S, Jones DM, Chen R, Taylor NG, Srinivasan P, Quan C, Roy DG, Steenbergen RH, Kumar A, Lyn RK, Özcelik D, Rouleau Y, Nguyen MA, Rayner KJ, Hobman TC, Tyrrell DL, Russell RS, Pezacki JP “MicroRNAs regulate the immunometabolic response to viral infection in the liver”, Nat. Chem. Biol. 2015, 11, 988-993.