Robert N. Husson
Division of Infectious Diseases
Department of Pediatrics
Enders Bldg., Room 761
300 Longwood Ave.
Boston, MA 02115
Lab Members: 4 postdoctoral fellows, 1 research assistant
Visit my lab page here.
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.
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. Microbiology 2008 154:725-735.
Park ST, Kang C-M, Husson RN. Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2008; 105:13105-13110.
Prisic A,Dankwa S, Schwartz D, Chou MF, Locasale J, Kang C-M, Bemis G, Church GM, Steen S, Husson RN. Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases. Proc Natl Acad Sci USA 2010: 107:7521-7526.
Mir M, Asong J, Li X, Cardot J, Boons G-J, Husson RN. The Extracellular Domain of the Mycobacterium tuberculosis Ser/Thr Kinase PknB Binds Specific Muropeptides and is Required for PknB Localization. PLoS Pathogens 2011; 7:e1002182. PMID: 21829358
For a complete listing of publications click here.
Last Update: 8/1/2012