Yao Liu

Immunology and inflammation research, bioassay development (ELISA, western blot, potency assay), and biologics characterization (RP/IEX/SEC-HPLC)

Small molecule drug discovery in inflammatory diseases and cancer • Novel target identification and validation • Design, develop and optimize reporter assays and immunoassays for HTS • Provide support for lead optimization by screening compounds • Conduct drug mechanism of action studies • Establish animal models of inflammatory diseases to measure the therapeutic efficacy of drug candidates • Perform large molecule bioanalysis of samples from cell lines, primary cells, plasma, muscle tissues treated with PTC small molecule compounds using ELISA, MSD, HTRF and flow cytometry

1 Bacille Calmette–Guérin (BCG), the only licensed vaccine against Mycobacterium tuberculosis, could cause potentially lethal infections in immunocompromised individuals. I developed a safer BCG vaccine which is safe to immunodeficient mice and have the potential to be used in immunocompromised people. • Designed a small molecule-controllable suicidal BCG vaccine • Assessed its safety using immunocompromised mouse model • Investigated the immune responses induced by the suicidal BCG vaccine using multi-color flow cytometry • Demonstrated that the suicidal BCG vaccine is safe for immunocompromised mice while retaining a similar protection efficacy against M. tuberculosis infection as the original BCG vaccine 2 Investigate the immunological determinants that regulate tuberculosis (TB) relapse Background: Infection with Mycobacterium tuberculosis (MTB) frequently results in latent tuberculosis infection (LTBI). Individuals with LTBI are at risk for developing active TB. However, studying LTBI was limited by the lack of a suitable mouse model • Established two genetic models of LTBI with different TB relapse rates in mice by transiently knockdown essential genes (bpl or trxB2) in Mycobacterium tuberculosis (MTB) • Identified immune signatures of T cells indicative of TB relapse using flow cytometry • Compared the blood transcriptomes of the two LTBI models using RNA-seq and identified differentially expressed genes using DESeq in R • A co-author paper was published in Journal of Experimental Medicine

Made multiple significant discoveries in understanding the virulence strategies employed by the intracellular bacterial pathogen Legionella pneumophila to survive inside mammalian professional phagocytes. Discovered and characterized post-translational modification mechanisms employed by bacterial virulence factors to subvert mammalian ubiquitination pathway and cell cytoskeleton. • Developed and performed genetic screenings using yeast (Saccharomyces cerevisiae) and mammalian cells as model systems to functionally characterize novel virulence factors (effector proteins) secreted by L. pneumophila • Identified a Legionella virulence factor (RavK) that remodels the mammalian cytoskeleton by cleaving actin • Identified a Legionella virulence factor (SidJ) that inhibits the activity of a phosphoribosyl ubiquitin ligase SdeA by a novel calmodulin-dependent glutamylation reaction • Contributed to elucidate the mechanism of a novel phosphoribosyl ubiquitination mediated by a single Legionella virulence factor SdeA Leadership/ Team Work • Trained two undergraduate students on mammalian cell culture, L. pneumophila infection, site-directed mutagenesis, protein purification, western blot and confocal fluorescence microscope. • Collaborated with a visiting student on multiple suppressor screens of toxic L. pneumophila effector proteins in yeast. • Led two highly collaborative projects - Collaboration with Dr. Ernesto S Nakayasu at Pacific Northwest National Laboratory (mass spectrometry) and Yuxin Mao lab at Cornell University (structure biology) on the biochemical characterization of two L. pneumophila effector proteins.