The research in my laboratory is currently focused on two main areas. For each project we are applying molecular techniques to animal models of experimental asthma to investigate asthma pathogenesis.
In the first project we are using recombinant retroviruses to generate gene-modified T cells with the capacity to deliver specific cytokines or molecules with therapeutic potential to the airways. The retrovirally transduced T cells that we generate express enhanced green fluorescent protein (EGFP), which allows us to track these cells following adoptive transfer into naïve recipient rats. We are investigating airway inflammation and smooth muscle remodeling in the Brown Norway rat model of adoptively transferred asthma. We have shown that adoptively transferred T cells expressing EGFP are present in the lungs following allergen challenge and some of them colocalize with airway smooth muscle cells. We have also generated T cells overexpressing the Th2 specific transcription factor, GATA-3, and shown that these cells promote enhanced eosinophilic airway inflammation. The ability of these cells to induce airway smooth muscle remodeling is currently under investigation.
For the second project we are using cell permeable peptides to inhibit signaling molecules whose aberrant activation contributes to allergic airways disease. We are investigating the ability of these peptides to inhibit airway inflammation, hyperresponsiveness, and remodeling in murine and rat models of asthma. We have tested a cell permeable peptide targeting the SH2 domain in the Th2 specific STAT-6 transcription factor. We have shown that a cell permeable STAT-6 inhibitory peptide (STAT-6-IP) inhibits STAT-6 activity in cultured cells as well as in a murine model of combined rhinitis and asthma. Experiments are in progress to define the mechanism by which the STAT-6-IP inhibits STAt-6 activity, both in vitro and in vivo.
RI-MUHC, Block E
1001 Decarie Blvd.
Montreal QC H4A 3J1
Tel: 514-934-1934 Ext. 76366 (lab)
Tel: 514-934-1934 Ext. 76242 (office)
Tel: 514-934-1934 Ext. 76172 (admin)
Education & Training
BSc (Chem/Biochem) Colorado State U (1986)
PhD (Pharmacology) Johns Hopkins (1992)
Adv Topics in Respiration (EXMD 508)