PhD; Professor
danuta.radzioch@muhc.mcgill.ca

Research interests

Our studies have utilized a very well-defined system of genetically determined differences in host response to bacterial infections. The analysis of the molecular basis of macrophage activation for effective bactericidal function requires access to homogenous cell populations of defined genetic background. We have made very significant progress towards this goal by the generation of macrophage cell lines from mouse strains which carry either the Nramp1r or Nramp1s allele, and from Nramp1-knockout mice, and by detailed biochemical comparison of these cell lines. Among other subjects, we have been investigating the basis of the differential expression of MHC class II proteins in macrophages derived from the mouse strains carrying the resistant allele of the Nramp1 gene compared to the macrophages that do not express this gene. We have found that the expression of class II transactivator CIITA is impaired in the latter macrophages due (at least in part) to a differential phosphorylation of STAT1¦Á protein in macrophages activated with IFN¦Ã. We have also been studying the mechanism of MHC class II gene expression modulation in macrophages infected with bacteria (Mycobacteria, Pseudomonas aeruginosa) and bacterial products (endotoxins, exotoxins, bacterial wall components). We are also studying the genetic basis of differential response to pharmacological activators that can help to defend the organism against infection with Mycobacteria. The ultimate significance of these studies lies in the usefulness of the results that may help devise a better rationale for therapeutic management of infections with Mycobacteria, including M. bovis, M. major and M. tuberculosis.

A substantial amount of effort of the laboratory is also devoted to studies of the mechanism of post-transcriptional regulation of TNFa gene expression in macrophages. We focused our studies on the interactions of TNF¦Á mRNA with macrophage proteins, likely mediators of this post-transcriptional control. We found and mapped a novel region within the 3'UTR of the TNF¦Á mRNA molecule that interacts with macrophage RNA-binding protein complexes. We have cloned several of these proteins and we are studying their role in the regulation of TNF¦Á mRNA stability, transport and TNF¦Á protein translation in activated macrophages.

Finally, we hypothesized that TNF¦Á is overproduced in the lungs during chronic infection with Pseudomonas aeruginosa and it is responsible, at least in part, for the increase in bacterial load and mortality in C57Bl-CFTR-knockout mice. The major objective of these studies is to characterize the regulation of TNF¦Á and its role in modulating inflammation during bronchopulmonary infection with Pseudomonas aeruginosa in CFTR-knockout mice. Knowledge derived from the proposed studies will be important for the development of novel therapeutical strategies for cystic fibrosis.

Awards

National Scholar (Rechercheur National)
Fonds de la Recherche en Santé du Québec
1999-2004

Order of the Unique Class
Central University of Venezuela
1997

First Award for Investigations in Basic Sciences
Faculty of Medicine, Central University of Venezuela
1996

Senior Scholarship
Fonds de la Recherche en Santé du Québec
1995-1999

Montreal General Hospital Research Institute Salary Award
Montreal, Quebec, Canada
1995-1996

Junior 2 Research Scholarship
Fonds de la Recherche en Santé du Québec
1994-1995

Young Investigator Award for Excellence in Leukocyte Biology Research
Society for Leukocyte Biology
1992

Junior Research Scholarship
Fonds de la Recherche en Santé du Québec
1990-1993

Fraser-Monat-McPherson Scholarship Award
Faculty of Medicine, McGill University
1989-1992

Program Resources Inc. Award for Outstanding Performance
Frederick, MD, USA
1987, 1988

Montreal General Hospital Research Institute Salary Award
Montreal, Quebec, Canada
1988-1989

Fulbright Scholarship
Foundation for the Advancement in the Sciences
(One of the two awardees in Health Sciences selected by US Scientific out of 2000 applicants)
1984-1986

Departmental affiliation

Division of Experimental Medicine; Department of Human Genetics

Accepting students from

Division of Experimental Medicine; Department of Human Genetics