On going research projects
The focus of the laboratory is to study the host-response to virus infections. Our research is aimed at deciphering the molecular mechanisms involved in the innate Interferon (IFN)-mediated antiviral/proinflammatory response mounted by the host against viruses that target the host mucosa.
We bring our expertise in the following goals:
- Role of redox metabolism in the regulation of the Interferon-mediated antiviral defense and proinflammatory response induced by viruses. We have identified the role of two isoforms of Reactive Oxygen Species (ROS)-generating enzymes NADPH oxidase, NOX2 and DUOX2, in the antiviral response against respiratory viruses in airway epithelial cells. Our effort is now to identify how ROS regulate the capacity of cells to mount an antiviral defense through redox post-tranlational modifications of key antiviral proteins. We use biochemical and proteomic analysis to characterize redox modifications of the proteome.
- Study the innate IFN response to Respiratory Syncytial Virus (RSV), the leading cause of pediatric respiratory virus infections. We aim to characterize the host mechanisms required for the replication of RSV and for the establishment of a efficient antiviral response. We also study the evasion mechanisms used by this virus to subvert the host defense. In this regards, we are particularly interested in the role of the NS1 and NS2 proteins of RSV.
- Synergism between IFNb and TNFa. We found that costimulation with IFNb and TNFa induces a broad antiviral and immunoregulatory transcriptional program in the absence of STAT1. Our recent findings highlight the role of distinct non-canonical STAT2 and/or IRF9 pathways in the regulation of distinct sets of genes. The overreaching goal of this research program is to decipher the molecular mechanisms which govern the specific and coordinated cellular response to IFNb+TNFa. Our goal is to further characterize the non-canonical functions of STAT2 and IRF9.
Past research projects
- IKKε in breast cancer: potential for redox-based therapeutic IKK-related kinases, IKKε and TBK1, have been shown to be essential to mount an interferon antiviral response. However, they are also found to be associated with cancer cell proliferation. Based on our work showing redox regulation of the antiviral response, we studied the potential of manipulated IKKe expression in breast cancer cells to decrease their proliferation. We found that cationic triphenylmethane dyes, Brilliant Green and Gentian Violet, and nitroxide Tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, a cell-permeant superoxide dismutase mimetic that is the lead compounds of a series of nitroxide that have antioxidant activities, mainly through free radical scavenging, reduced IKKe levels and breast cancer cells proliferation.
We studied IKKε expression by immunohistochemistry (IHC) using tissue microarrays of 154 human breast cancer tissues and analyzed the association with clinicopathological parameters and with a panel of biomarkers used for molecular classification of tumors. IKKε expression was found inversely associated with lymph node metastasis status. Additionally, we identified a novel association between IKKε and EGFR expression.