1650 Cedar Ave. Room RS1-133
Office phone: (514) 934-1934 x43641
michael [dot] reed [at] mcgill [dot] ca
Link to Pubmed
The research of my laboratory focuses on molecular aspects of the pathogenesis of Mycobacterium tuberculosis, the bacterial agent responsible for the infectious disease, tuberculosis (TB). Despite the existence of effective antibacterial drugs and a partially effective vaccine for more than half a century, TB still remains the cause of 2 million deaths worldwide each year - the most due to any single infectious agent. This situation reflects very poorly on the current level of understanding of the pathogenic processes associated with this important pathogen.
Although early studies considered TB strains to be restricted in terms of their genetic and antigenic variability, more recent evidence indicates that M. tuberculosis has evolved into several genetically diverse lineages of strains that are likely to possess unique attributes related to the transmission and development of disease. My laboratory utilizes a range of molecular biology, biochemical, microbiological and immunological techniques to investigate the array of metabolic and virulence strategies available to this phenotypically diverse pathogen. Increasing our knowledge and understanding of this diversity will greatly enhance future efforts aimed at developing new strategies to successfully diagnose and treat TB disease.
Two major research themes of my laboratory are:
M. tuberculosis strain variability - the “Beijing” lineage.
One family of TB strains that has gained considerable notoriety over the past decade is known as the “Beijing” family. In many regions of the world, TB incidence due to Beijing strains is found to be increasing in an epidemic fashion. Moreover, in many of these countries infection due to these strains is frequently associated with the development of drug resistance. Two avenues of research into the mechanisms underlying Beijing strain pathogenesis are currently underway in my laboratory.
(1) We have recently demonstrated that all members of this strain family share the ability to constitutively over-express a transcriptional program controlled by the DosS-DosR two-component regulatory system. This regulon is associated with environmental sensing of oxygen by the bacterium and is likely to be one of the key pathways leading to the development of latent TB infection. Ongoing work in my laboratory will continue to uncover the role of the DosS-DosR regulon in shaping the unique virulence and epidemiological properties attributed to the Beijing strain family.
(2) A second unique characteristic of the Beijing strains is their ability to produce a complex, polyketide synthase-derived lipid known as phenolic glycolipid (PGL-tb). Production of this immunosuppressive lipid inhibits pro-inflammatory cytokine release by host macrophages and results in a “hypervirulence” phenotype in animal models of TB infection. We are currently attempting to identify the macrophage receptors and signaling pathways that interact with the PGL-tb glycolipid and that result in suppression of the host’s innate immune response.
Antigenic variation and M. tuberculosis lipids
The majority of M. tuberculosis virulence factors described to-date include the various waxes and glycolipids associated with the multi-layered, lipid-rich cell wall that plays a central role in defining the unique biological and physical characteristics of the Mycobacteria. My laboratory is actively pursuing the characterization of lipids that are uniquely produced within genetically distinct lineages of TB and that contribute to the evolution of M. tuberculosis antigenic and pathogenic diversity. An understanding of the biosynthetic pathways leading to the formation of these lipids, as well as the nature of their interaction with cells of the host, may shed valuable light on potential novel approaches to prevent the ongoing cycle of transmission and disease associated with this globally successful pathogen.
Department of Medicine; Department of Microbiology and Immunology
Accepting students from
Medicine; Microbiology and Immunology