A critical barrier to the development of better TB control strategies has been insufficient knowledge of how Mtb alters the host immune system to cause infection. Dr. Zakaria Hmama’s team has been investigating the subcellular and molecular mechanisms of host/pathogen interactions over the last six years. Their efforts have revealed subtle strategies used by pathogenic mycobacteria to invade the macrophage and attenuate critical functions such as intracellular killing and stimulation of T cell mediated specific immune response. In vitro studies also revealed that the BCG vaccine mimics the effects of virulent mycobacteria, which explains its low efficacy in TB prevention.
Ongoing research in the Hmama lab builds on original and innovative projects that challenge existing TB prevention and treatment practices. Dr. Hmama’s laboratory is developing novel gene manipulation technologies to upgrade the current BCG vaccine in order to maximize the induction of protective TB immunity. Of equal importance to the vaccine project, a biology-based study of Mtb persistence has revealed important virulence factors that represent attractive drug targets that could be used for TB treatment.
University: University of British Columbia
Position: Associate Professor
Research Location: Jack Bell Research Centre
Wong D, Bach H, Sun J, Hmama Z, Av-Gay Y. Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19371-6. doi: 10.1073/pnas.1109201108. Epub 2011 Nov 15. (PubMed abstract)
Sun J, Wang X, Lau A, Liao TY, Bucci C, Hmama Z. Mycobacterial nucleoside diphosphate kinase blocks phagosome maturation in murine RAW 264.7 macrophages. PLoS One. 2010 Jan 19;5(1):e8769. doi: 10.1371/journal.pone.0008769. (PubMed abstract)
Sun J, Lau A, Wang X, Liao TY, Zoubeidi A, Hmama Z. A broad-range of recombination cloning vectors in mycobacteria. Plasmid. 2009 Nov;62(3):158-65. doi: 10.1016/j.plasmid.2009.07.003. Epub 2009 Jul 30. (PubMed abstract)
Bach H, Papavinasasundaram KG, Wong D, Hmama Z, Av-Gay Y. Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe. 2008 May 15;3(5):316-22. doi: 10.1016/j.chom.2008.03.008. (PubMed abstract)
Soualhine H, Deghmane AE, Sun J, Mak K, Talal A, Av-Gay Y, Hmama Z. Mycobacterium bovis bacillus Calmette-Guérin secreting active cathepsin S stimulates expression of mature MHC class II molecules and antigen presentation in human macrophages. J Immunol. 2007 Oct 15;179(8):5137-45. (PubMed abstract)
Type Scholar Award
Type Scholar Award