Education & Certifications

  • Master of Science, Stanford University, BIOE-MS (2018)
  • Bachelor of Applied Science, University of Ottawa, Chemical Engineering (2016)
  • Bachelor of Science, University of Ottawa, Biochemistry (2016)

All Publications

  • MicroRNA-7 mediates cross-talk between metabolic signaling pathways in the liver. Scientific reports Singaravelu, R., Quan, C., Powdrill, M. H., Shaw, T. A., Srinivasan, P., Lyn, R. K., Alonzi, R. C., Jones, D. M., Filip, R., Russell, R. S., Pezacki, J. P. 2018; 8 (1): 361


    MicroRNAs (miRNAs) have emerged as critical regulators of cellular metabolism. To characterise miRNAs crucial to the maintenance of hepatic lipid homeostasis, we examined the overlap between the miRNA signature associated with inhibition of peroxisome proliferator activated receptor-α (PPAR-α) signaling, a pathway regulating fatty acid metabolism, and the miRNA profile associated with 25-hydroxycholesterol treatment, an oxysterol regulator of sterol regulatory element binding protein (SREBP) and liver X receptor (LXR) signaling. Using this strategy, we identified microRNA-7 (miR-7) as a PPAR-α regulated miRNA, which activates SREBP signaling and promotes hepatocellular lipid accumulation. This is mediated, in part, by suppression of the negative regulator of SREBP signaling: ERLIN2. miR-7 also regulates genes associated with PPAR signaling and sterol metabolism, including liver X receptor β (LXR-β), a transcriptional regulator of sterol synthesis, efflux, and excretion. Collectively, our findings highlight miR-7 as a novel mediator of cross-talk between PPAR, SREBP, and LXR signaling pathways in the liver.

    View details for PubMedID 29321595

    View details for PubMedCentralID PMC5762714

  • MicroRNAs regulate the immunometabolic response to viral infection in the liver NATURE CHEMICAL BIOLOGY Singaravelu, R., O'Hara, S., Jones, D. M., Chen, R., Taylor, N. G., Srinivasan, P., Quan, C., Roy, D. G., Steenbergen, R. H., Kumar, A., Lyn, R. K., Ozcelik, D., Rouleau, Y., Nguyen, M., Rayner, K. J., Hobman, T. C., Tyrrell, D. L., Russell, R. S., Pezacki, J. P. 2015; 11 (12): 988-993


    Immune regulation of cellular metabolism can be responsible for successful responses to invading pathogens. Viruses alter their hosts' cellular metabolism to facilitate infection. Conversely, the innate antiviral responses of mammalian cells target these metabolic pathways to restrict viral propagation. We identified miR-130b and miR-185 as hepatic microRNAs (miRNAs) whose expression is stimulated by 25-hydroxycholesterol (25-HC), an antiviral oxysterol secreted by interferon-stimulated macrophages and dendritic cells, during hepatitis C virus (HCV) infection. However, 25-HC only directly stimulated miR-185 expression, whereas HCV regulated miR-130b expression. Independently, miR-130b and miR-185 inhibited HCV infection. In particular, miR-185 significantly restricted host metabolic pathways crucial to the HCV life cycle. Interestingly, HCV infection decreased miR-185 and miR-130b levels to promote lipid accumulation and counteract 25-HC's antiviral effect. Furthermore, miR-185 can inhibit other viruses through the regulation of immunometabolic pathways. These data establish these microRNAs as a key link between innate defenses and metabolism in the liver.

    View details for DOI 10.1038/NCHEM.BIO.1940

    View details for Web of Science ID 000365834000019

    View details for PubMedID 26479438

  • Armand-Frappier Outstanding Student Award - The emerging role of 25-hydroxycholesterol in innate immunity CANADIAN JOURNAL OF MICROBIOLOGY Singaravelu, R., Srinivasan, P., Pezacki, J. P. 2015; 61 (8): 521-530


    The metabolic interplay between hosts and viruses plays a crucial role in determining the outcome of viral infection. Viruses reorchestrate the host's primary metabolic gene networks, including genes associated with mevalonate and isoprenoid synthesis, to acquire the necessary energy and structural components for their viral life cycles. Recent work has demonstrated that the interferon-mediated antiviral response suppresses the sterol pathway through production of a signalling molecule, 25-hydroxycholesterol (25HC). This oxysterol has been shown to exert multiple effects, both through incorporation into host cellular membranes as well as through transcriptional control. Herein, we summarize our current understanding of the multifunctional roles of 25HC in the mammalian innate antiviral response.

    View details for DOI 10.1139/cjm-2015-0292

    View details for Web of Science ID 000358786800001

    View details for PubMedID 26182401

  • Soraphen A: A Probe for Investigating the Role of de Novo Lipogenesis during Viral Infection ACS INFECTIOUS DISEASES Singaravelu, R., Desrochers, G. F., Srinivasan, P., O'Hara, S., Lyn, R. K., Mueller, R., Jones, D. M., Russell, R. S., Pezacki, J. P. 2015; 1 (3): 130-134
  • Hepatitis C Virus Induced Up-Regulation of MicroRNA-27: A Novel Mechanism for Hepatic Steatosis HEPATOLOGY Singaravelu, R., Chen, R., Lyn, R. K., Jones, D. M., O'Hara, S., Rouleau, Y., Cheng, J., Srinivasan, P., Nasheri, N., Russell, R. S., Tyrrell, D. L., Pezacki, J. P. 2014; 59 (1): 98-108


    MicroRNAs (miRNAs) are small RNAs that posttranscriptionally regulate gene expression. Their aberrant expression is commonly linked with diseased states, including hepatitis C virus (HCV) infection. Herein, we demonstrate that HCV replication induces the expression of miR-27 in cell culture and in vivo HCV infectious models. Overexpression of the HCV proteins core and NS4B independently activates miR-27 expression. Furthermore, we establish that miR-27 overexpression in hepatocytes results in larger and more abundant lipid droplets, as observed by coherent anti-Stokes Raman scattering (CARS) microscopy. This hepatic lipid droplet accumulation coincides with miR-27b's repression of peroxisome proliferator-activated receptor (PPAR)-α and angiopoietin-like protein 3 (ANGPTL3), known regulators of triglyceride homeostasis. We further demonstrate that treatment with a PPAR-α agonist, bezafibrate, is able to reverse the miR-27b-induced lipid accumulation in Huh7 cells. This miR-27b-mediated repression of PPAR-α signaling represents a novel mechanism of HCV-induced hepatic steatosis. This link was further demonstrated in vivo through the correlation between miR-27b expression levels and hepatic lipid accumulation in HCV-infected SCID-beige/Alb-uPa mice.Collectively, our results highlight HCV's up-regulation of miR-27 expression as a novel mechanism contributing to the development of hepatic steatosis.

    View details for DOI 10.1002/hep.26634

    View details for Web of Science ID 000328738400014

    View details for PubMedID 23897856

  • Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Singaravelu, R., Lyn, R. K., Srinivasan, P., Delcorde, J., Steenbergen, R. H., Tyrrell, D. L., Pezacki, J. P. 2013; 441 (2): 447-452


    Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB's role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB's role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway's role in LD dynamics and the VLDL pathway.

    View details for DOI 10.1016/j.bbrc.2013.10.080

    View details for Web of Science ID 000327290100029

    View details for PubMedID 24161736