Biological and Biomedical Science
 DMS Home  /  About DMS  /  Current Student Resources  /  Contact Us  /  Search 

Robert N. Husson

Department of Pediatrics
Division of Infectious Diseases
Children's Hospital
Enders Building, Room 761
300 Longwood Avenue
Boston, MA 02115
Tel: (617) 919-2883
Fax: (617) 730-0254
Email: robert.husson@childrens.harvard.edu
4 postdoctoral fellows, 1 research scientist, 1 research assistant


Mycobacterium tuberculosis remains a major human pathogen, causing roughly 8 million new cases of active tuberculosis (TB) annually, mostly in the developing world where it is the leading cause of mortality in HIV-infected persons. TB disease results from a prolonged and complex interaction between the bacterium and the host. My laboratory studies the regulatory mechanisms that allow M. tuberculosis to adapt to host environments during the course of infection.

One focus of our research is the regulation of M. tuberculosis gene expression by alternative sigma factors, including those that regulate virulence determinants and stress adaptation. We have characterized a regulatory network involving at least three alternative sigma factors (SigE, SigH and SigB) that is critical for the response to oxidative stress and for virulence. Additional studies have elucidated regulation of surface lipid and secreted protein determinants of virulence by two other sigma subunits. Current work aims to further define these regulons, including the functions of specific sigma-regulated genes involved in these stress responses and in pathogenesis.

The second major focus of our research is signal transduction in M. tuberculosis mediated by eukaryotic-like serine/threonine kinases. We have demonstrated a role for two of these signaling molecules, PknA and PknB, in regulation of cell shape and cell division, and identified in vivo substrates of these kinases. Ongoing work aims to define the functions of these kinase targets and the ways in which reversible phosphorylation modulates these functions. A broad, proteomic approach to kinase substrate identification is also underway in the laboratory.

 

References:

  • Kang C-M, Nayapathy S, Lee J-Y, Suh J-S, Husson RN. Wag31, a homolog of the cell division protein DivIVA, regulates growth, morphology and polar cell wall synthesis in mycobacteria. Micriobiology 2008 154:725-735.

  • Raman S, Puyang X, Cheng T-Y, Young DC, Moody DB, Husson, Robert N. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and non-ribosomal peptide biosynthesis genes, and down-regulates virulence-associated surface lipid synthesis. J Bacteriol 2006; 188:8460-8468.

  • Kang C-M, Abbott DW, Park ST, Dascher CC, Cantley LC, Husson RN. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape. Genes Dev 2005; 19: 1692-1704.

  • Song T, Dove SL, Lee KH, Husson, RN. RshA, an anti-sigma factor that regulates the activity of the mycobacterial stress response sigma factor SigH. Mol Micro 2003;50:949-959.