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Research

Members of the group are involved in molecular, cellular, genetic and translational studies in various areas of cancer biology, including: 

 

Drug Resistance & Metabolism

Chemotherapy of many types of cancer fails to achieve a cure either because the tumors are inherently resistant to a wide range of cytotoxic drugs and differentiating agents, or they acquire such characteristics following an initial response. We are involved in the identification, cloning and characterization of proteins responsible for these resistance mechanisms. Studies to date have resulted in discovery of: the Multidrug Resistance Protein (MRP) which is capable of conferring resistance to a wide range of commonly used natural product chemotherapeutic agents; topoisomerase II mutations that reduce its nuclear localization causing resistance to drugs targeting this enzyme; a candidate protein that may be involved in development of resistance to platinum based drugs; CYP26 which is a novel retinoid inducible cytochrome P450 that may catalyze the rate limiting step in retinoid catabolism, and a mechanism by which xenobiotics can induce changes in expression of the major serum high density apolipoprotein, ApoAI, that may enhance hepatic elimination of these compounds. More detailed information can be obtained from the personal pages of individual investigators.

 

Susan P.C. Cole
Mechanisms of Resistance to Anticancer Drugs and Transport of Chemical Toxicants 

Roger G. Deeley
Gene Expression/Drug Resistance 

P. Martin Petkovich
Retinoic Acid Receptors in Development and Differentiation

Tumor Progression

The initiation and progression of cancer is a multistep process involving both genetic alterations and changes in tissue microenvironment. These genetic and cellular events result in dysfunction of normal cell growth and differentiation allowing the development of the malignant phenotype. We are investigating the molecular mechanisms which disrupt differentiation, allowing the reestablishment of growth ability, and stromal-tumour cell interactions which then promote this growth and eventual metastasis. The transcriptional regulation of the BRCA1 gene and the possibility that its regulation is involved in sporadic breast cancer is also being studied. As well, growth factors such as hepatocyte growth factor (HGF) show increased expression in regions of carcinoma in human breast, compared to surrounding nonmalignant tissue. In vitro studies indicate that establishment of an HGF autocrine loop in breast carcinoma cells is an important step in progression to metastasis. Mechanisms involved in the regulation of HGF expression and function in breast carcinoma cells are being investigated. See personal pages of individual investigators for more detailed information.

 

Andrew Craig
Cancer metastasis pathways

Bruce E. Elliott
Growth Factors and Cell Adhesion
Molecules in Breast Cancer 

Christopher R. Mueller
Transcription Factors in Growth and Development

Christopher J. Nicol
Involvement of PPAR(gamma) in breast and colon cancer

Cell Growth Proliferation & Differentiation

Normal development requires the coordination of a wide variety of events that determine the growth, specialization and ultimately, the death of the cell. We are characterizing the underlying molecular mechanisms which control these processes and are determining the relationship between defects in key genes and the etiology of cancer. Regulation at both the level of cytoplasmic signal transduction and nuclear signaling by nuclear receptors, transcription factors, and DNA topoisomerases is being studied. Specific interests include the role of retinoic acid and steroid hormones in development, control of the cell cycle and DNA damage-induced checkpoints, regulation of hematopoiesis, angiogenesis and vasculogenesis, nucleocytoplasmic trafficking of topoisomerase II, liver development and regeneration. This work emphasizes the use of molecular biology in conjunction with a variety of model systems including yeast, zebrafish and transgenic mice as well as cultured cells from a number of species.  See personal pages of individual investigators for more detailed information.

 

Susan P.C. Cole
Mechanisms of Resistance to Anticancer Drugs and Transport of Chemical Toxicants 

Scott K. Davey
Cell Cycle Checkpoint Control and DNA Repair 

Roger G. Deeley
Gene Expression/Drug Resistance

Peter A. Greer
Transgenic Mouse Models of Proto-oncogene Function

David P. LeBrun
Mechanistic and Correlative Research in Leukemia and Lymphoma

Christopher R. Mueller
Transcription Factors in Growth and Development

Lois M. Mulligan
Role of the RET Proto-oncogene in Neoplastic Growth

Christopher J. Nicol
Involvement of PPAR(gamma) in Breast and Colon Cancer

P. Martin Petkovich
Retinoic Acid Receptors in Development and Differentiation