Robert Lafrenie, Ph.D.
Career Scientist &
Laboratory Director

Current Positions
Laboratory Director, Tumour Biology Seminar Series Co-ordinator and Career Scientist, Regional Cancer Program of the Hôpital Régional de Sudbury Regional Hospital, Sudbury, Ontario

Associate Professor, Department of Chemistry and Biochemistry, and Department of Biology, Laurentian University, Sudbury, Ontario

Associate Professor, Program in Biomolecular Sciences, Laurentian University, Sudbury, Ontario

Associate Professor, Division of Medical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario

Education/Training
1993-1997 Visiting Fellow, National Institute of Dental Research, National Institutes of Health

1988-1994 Ph.D. McMaster University, Medical Sciences

1986-1989 M.Sc. McMaster University, Medical Sciences

1979-1984 B.Sc. University of British Columbia, Biochemistry

Research Investigations
Cell Adhesion alters Cellular Signals and Gene Expression 
Adhesion of cells to extracellular matrix is an important regulator of both cellular differentiation and carcinogenesis. The adhesion of cells to extracellular matrix is mediated primarily by integrin cell surface receptors.  We have shown that the adhesive interaction of non-malignant human cells with extracellular matrix can regulate cell growth, promote the expression of a large number of different genes, and is central to cellular differentiation. Further, we have shown that integrin-dependent adhesion activates multiple cellular signal transduction pathways and that this activation mediates the changes in gene expression. Monocyte adhesion to extracellular matrix via cell surface integrin adhesion molecules leads to significant changes in the expression and synthesis of inflammatory mediators such as cytokines and proteases. Continuing work in the laboratory is focused on determining the role of the protein kinase C and MAP kinase pathways in these signaling cascades. Preliminary results suggest that this is a very complex process and that adhesion-dependent expression of different genes may be regulated by different mechanisms. Therefore, it seems likely that the regulation of cellular differentiation or carcinogenesis is also a complex signaling process which involves interactions between several different signaling pathways.

Prognostic Indicators for Women with Breast Cancer
Breast cancer affects about 1/9 women in North American and approximately 1/3 of those women go on to develop metastatic disease. However, the number of women who die from breast cancer is decreasing in North America where early diagnosis and improved treatments are available. The success of a specific treatment for patients with metastatic breast cancer can vary significantly from one patient to another. These inter-individual variations in chemotherapeutic efficacy and clinical outcome are influenced by genetic differences between individuals. In vitro and in vivo studies have shown that variations in the genes and/or proteins that are involved in DNA repair, drug metabolism, drug transport, and cell cycle control are associated with different sensitivities to a broad range of drugs. Single nucleotide polymorphisms (SNPs) in the genes involved in DNA repair, drug metabolism, and cell cycle control pathways have been identified and studies have shown that small genetic variations can affect repair efficiency, increase cancer risk and significantly alter patient responses to cancer treatment. Several studies show that having an increasing number of variant alleles in the genes involved in chemotherapy-related pathways can significantly influence survival following treatment for cancer. We have been measuring individual differences in sequence (SNPs) in genes that are involved in DNA repair, carcinogen detoxification, and inflammation and differences in protein expression levels for growth and inflammatory markers in women with breast cancer. We have then correlated these differences to relative patient prognosis. The goal of these approaches is to identify biomarkers that predict responses to therapy and relative clinical outcome for patients with metastatic breast cancers.

Evaluation of natural health products in the treatment and control of cancers 
Despite largely stable population rates, the total number of new cancer cases and deaths continue to rise steadily as the Canadian population grows and ages. Chemotherapy and radiation therapy target cells undergoing rapid proliferation, like cancer cells, but also damage normal cells. This can induce a host of unpleasant and often debilitating side effects. Current evidence suggests that a shift from reactive treatment to cancer prevention would be of benefit. A wealth of evidence points to diet as one of the most important modifiable determinants of cancer risk Further, many patients are including natural health products in their diets as these products are developed and promoted although the mechanisms of action and efficacy of these components is frequently unknown. Current research in our laboratory is aimed at determining the mechanisms of action of two widely used natural health products: the Peruvian medicinal herb, Uncaria tomentosa, and the omega-3 fatty acid rich flax seed oil. We have shown that treatment of cultured cells with extracts of these natural products inhibits cells growth and may enhance susceptibility to death. To determine the mechanisms of action of these compounds, we have been measuring their effects on the activation of cellular signaling pathways that mediate changes in cell growth and susceptibility to apoptosis.

Jordana Fera, Alison Buckner, Rob Lafrenie and Carly Buckner

Ranji Singh
Research Technician