Research Summary

Our lab is engaged in both basic and translational research emphasizing mycobacterial genetics and biochemistry with the aim to develop new drugs in collaboration with industry and other academic groups. Our focus is primarily in tuberculosis (TB) research, studying signal transduction in Mycobacterium tuberculosis (Mtb) and understanding the intracellular lifestyle of Mtb in order to develop new and better drugs that can target Mtb in its natural environment in the Human host.

Projects
  • Molecular analysis of Mycobacterium tuberculosis kinases and phosphatases. Their role in TB pathophysiology, macrophages infection, antibiotic resistance and persistence.
  • Identification and characterization of novel compounds acting against Mycobacterium tuberculosis inside macrophages (in collaboration with GSK). Analysis of their physiological targets and mode of action.
  • Developing new screening methods and carrying screening assays testing natural products (With Prof. Raymond Anderson) and compounds libraries to identify novel drugs against the nontuberculous mycobacterial (NTM) cystic fibrosis pathogen, M. abscessus.
Bio

Dr. Yossef Av-Gay is a professor of Microbiology and Infectious Diseases in the Faculty of Medicine. He is also an associate member of the Department of Microbiology and Immunology and holds an adjunct professorship at the medical school of Ben Gurion University of the Negev, Israel. A microbiologist by training, his research interests lie with microbial disease mechanisms causing chronic lung infections, primarily tuberculosis (TB), followed by nontuberculous mycobacteria (NTM) diseases . He explores molecular events that govern host-pathogen interactions and the ability of mycobacteria to block the immune response to infection. Dr. Av-Gay’s research is geared towards the identification and characterization of novel drugs and drug targets in Mycobacterium tuberculosis. Dr. Av-Gay’s most significant discovery was the identification and characterization of PtpA, a protein phosphatase in Mtb which inhibits the normal macrophage response to infection.

Prof. Av-Gay received his BSc in Biology, MSc in Microbiology, and PhD in Microbial Genetics – all from Tel Aviv University, Tel Aviv, Israel, and advanced training at John Innes Institute, Norwich, UK, Albert Einstein Collage of Medicine, New York and UBC Microbiology.

Prof. Av-Gay authored over 100 peer review scientific publications, review articles, book chapters and 15 patents. Prof. Av-Gay served as an editor for the Journal of Biological Chemistry (2010-2015), and on scientific advisory boards of several biotechnology companies. Prof. Av-Gay is a member of the scientific review panels of the Canadian Institute of Health Research (Microbiology and Infectious Disease (2009-2016) and Foundation and Project Grants (2016-) , the French Agence Nationale de la Recherche, Innovative Medicine Innovations, The UK welcome Trust, US National Institute of Health, and the European Commission FP6, FP7 and Horizon 2020 programs.

Publications

Comprehensive List

Google Scholar

Selected Publications

  1. Richard-Greenblatt, M and Av-Gay, Y. (2017). Epigenetic Phosphorylation Control of Mycobacterium tuberculosis Infection and Persistence. Microbiol Spectrum TBTB2-0005-2015. doi:10.1128/microbiolspec.TBTB2-0005-2015.
  2. Sorrentino F., Gonzalez del Rio R., Zheng, X., Matilla, J.P., Torres Gomez, P., Hoyos, M.M., Perez Herran. M, E., Mendoza Losana, A., Av-Gay, Y. (2015). Development of an intracellular screen for new compounds able to kill Mycobacterium tuberculosis in human macrophages. Antimicrob Agents Chemother. 60(1):640-5.
  3. Poirier, V. and Av-Gay, Y. (2015). Intracellular Growth of Bacterial Pathogens: The Role of Secreted Effector Proteins in the Control of Phagocytosed Microorganisms. Microbiol Spectr. 2015 doi: 10.1128/microbiolspec.VMBF-0003-2014.
  4. Richard-Greenblatt M, Bach H, Adamson J, Pena-Diaz S, Wu L, Steyn AJ, Av-Gay, Y. (2015). Regulation of Ergothioneine Biosynthesis and its effect on Mycobacterium tuberculosis Growth and Infectivity. J Biol Chem. 2015. 18;290(38):23064-76.
  5. Hmama, Z., S,J. Pena. S, Joseph and Y. Av-Gay. (2015). Immunoevasion and immunosuppression of the Macrophage by Mycobacterium tuberculosis. Immunological reviews. 263(1): 220-232.
  6. Poirier V, Bach H, Av-Gay Y. (2014). Mycobacterium tuberculosis Promotes Anti-Apoptotic Activity of the Macrophage by PtpA- Dependent Dephosphorylation of Host GSK3α. J. Biol. Chem. 289(42): 29376-85
  7. Chao JD, Wong D, Av-Gay Y. Microbial Tyrosine Kinases. (2014) J Biol Chem. 289(14):9463-9472.
  8. Gómez-Velasco, A., Bach, H., Rana, K. A., Cox, R.L., Bhatt, A., Besra, S, G., and Av-Gay. Y. (2013). Disruption of the Serine Threonine Protein Kinase H affects Phthiocerol Dimycocerosates Synthesis in Mycobacterium tuberculosis. Microbiology. 159:726-36.
  9. Wong, D., Chao, J.D., and Av-Gay, Y. Mycobacterium tuberculosis-secreted phosphatases: from pathogenesis to targets for TB drug development. (2013). Trends in Microbiology. 21:100-109
  10. Lam KK, Zheng X, Forestieri R, Balgi AD, Nodwell M, Vollett S, Anderson HJ, Andersen RJ, Av-Gay Y, Roberge M. Nitazoxanide Stimulates Autophagy and Inhibits mTORC1 Signaling and Intracellular Proliferation of Mycobacterium tuberculosis. (2012). PLoS Pathog. May;8(5):e1002691.
  11. Wong, D., Bach, H., Sun, J., Hmama, Z., and Av-Gay, Y. (2011). Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. PNAS. 108,19371-19376.
  12. Chao JD, Papavinasasundaram KG, Zheng X, Chávez-Steenbock A, Wang X, Lee GQ, Av-Gay, Y. (2010). Convergence of Ser/Thr and two-component signaling to coordinate expression of the dormancy regulon in Mycobacterium tuberculosis. J Biol Chem. 285(38):29232-29246.
Office
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