Sébastien Tabariès Ph.D.
RESEARCH PROJECT
I have developed a strong research interest in elucidating the molecular mechanisms that drive cancer initiation and progression to metastatic disease. In 2006, I joined the laboratory of Dr. Siegel, which focuses on breast cancer, the most commonly diagnosed malignancy among Canadian women. My research aims to identify genes that regulate the metastatic capacity of breast cancer cells, particularly their ability to colonize and proliferate within the liver.
To address this objective, we employed the 4T1 murine mammary carcinoma cell line as a model system to investigate gene expression programs associated with liver metastasis. Through three successive rounds of splenic injection, we selectively enriched for breast cancer cells with enhanced liver tropism and aggressive growth characteristics. Gene expression profiling of explanted metastatic cells was subsequently performed to identify differentially expressed genes associated with the liver-metastatic phenotype. These analyses identified Claudin-2 (CLDN2) as a key mediator of breast cancer liver metastasis.
Consistent with our findings, CLDN2 has since been implicated as a critical regulator of colorectal cancer metastasis to the liver and is associated with poor prognosis in replacement-type liver metastases. Collectively, these observations highlight Claudin-2 as a promising therapeutic target for the treatment of solid tumors that metastasize to the liver. Accordingly, we have generated and characterized a panel of Claudin-2–specific antibodies, two of which have been developed as therapeutic candidates and are currently being evaluated for safety and efficacy in preclinical models.
BACKGROUND
Through the course of my career, I have pursued training opportunities in diverse fields, ranging from fundamental to applied research. I have helped define the molecular structure of the Annexin II-p11 complex, which is implicated in membrane fusion during exocytosis/endocytosis, and as a result have become proficient with numerous biochemistry techniques including chromatography (HPLC, FPLC), crystallogenesis, immunoblotting and immunoprecipitation (INSERM, Institut Cochin de Genetique Moleculaire, France). I subsequently moved to the pharmaceutical industry, using microarray and real-time PCR technologies to identify new therapeutic targets responsible for the development of cancer cell resistance to chemotherapy (Les laboratoires Pierre Fabre, France) and the application of these approaches to the study of type II diabetes (Lipha S.A., France).
During my Ph.D. degree, under the supervision of Dr. Lucie jeannotte (Université Laval, Québec), I have learned techniques necessary for the generation of defined mutations in genetically engineered mouse models. I designed a conditional mutant mouse to study of the role of the Hoxa5 gene during murine development and defined regulatory sequences that control the regionalization of Hoxa5 expression in the developing embryo. This phase of my training provided me with practical skills in molecular and cellular biology techniques such as cloning, DNA footprinting, PCR, Northen blotting, Southern blotting, the generation and maintenance of transgenic mouse lines, mouse embryo micro-dissection and stem cell culture.
CONTACT INFO
Rosalind and Morris Goodman Cancer Institute - McGill University
1160 Pine Ave. West (Room 508)
Montreal, Quebec (Canada)
H3A 1A3
T. 514.398.8889
F. 514.398.6769