Janetta Bijl

TITLE

• Assistant Professor

EDUCATION

• Research Investigatorship, IRCM/IRIC, Montreal (2002-2006).
• Postdoctorate, IRCM, Montreal (1997-2002).
• Ph.D., Vrije Universiteit Amsterdam, Amsterdam (1991-1997).

RESEARCH INTERESTS

The main objectives of the laboratory are to investigate the role of Homeobox (Hox) genes in the regulation of hematopoiesis and in human leukemia. Hox genes are transcription factors that originally were found as master control genes in the formation of the embryonic body plan. Multiple Hox genes are expressed in hematopoietic stem cell and progenitor fractions and aberrant expression of several members of the gene family have been associated with several types of leukemia. So far, it is not clear whether Hox genes are critical for hematopoiesis and which members are implicated in specific hematopoietic regulatory functions as lineage commitment, self-renewal, differentiation/proliferation and homing.

One of the projects in the lab aims to address these issues using a conditional knock-out mouse model. The gene Hoxb4 has been identified as a potent factor to expand hematopoietic stem cells with the conservation of its specific characteristics. As numbers of HSCs are limiting the in vitro expansion of this population has a huge impact on autologous bone marrow transplantations. However, Hoxb4 appears not essential for self-renewal of HSCs and other Hox genes are suspected to possess similar properties as Hoxb4. We aim to identify other Hox genes that could expand HSCs more efficiently than Hoxb4 or in combination with Hoxb4.

To study Hox gene involvement in leukemia we are exploiting a transgenic mouse model for human pre-B cell leukaemia induced by the fusion protein E2a-PBX1. A proviral insertional mutagenesis approach will be applied to identify collaborator oncogenes and dissect the molecular pathways underlying this disease. Furthermore, efforts are undertaken to identify partners in protein complexes containing the oncogene E2a-PBX or HOX proteins that might be potential targets for new therapies for leukemia.

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RESEARCH TEAM

• Marilaine Fournier, Ph.D. student
• Charles-Etienne Lebert Ghali, Ph.D. student
• Heloise Frison, M.Sc. student
• Elena Shestakova, Research Associate

Selected papers

Thorsteinsdottir U., Mamo A., Kroon E., Jerome L., Bijl J.J., Lawrence H.J., Humphries K., and Sauvageau G. Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood. 2002 Jan 1;99(1):121-9.

Bijl J.J., Sauvageau M., Thompson A. and Sauvageau G. High Incidence of Proviral Integrations in the Hoxa Locus in a New Model of E2a-PBX1-Induced B-Cell Leukemia. Genes & Dev. 2005 Jan 15; 19:224

Bijl J.J., Thompson A., Ramirez-Solis R., Krosl J. Grier D., Lawrence H.J. and Sauvageau G. Analysis of HSC Activity and Compensatory Hox Gene Expression Profile in Hoxb Cluster Mutant Fetal Liver Cells. Blood 2006 July 1; 108(1):116.

Mamo A., Krosl J., Kroon E., Bijl JJ., Thompson A., Mayotte N., Beslu N., Featherstone M. and Sauvageau G. Molecular Dissection of Meis1 Reveals Two Nucleating Domains for Leukemia Induction and a Key Role for Hoxa Gene Activation. Blood 2006 July 15; 108(2):622.

Bijl J., Krosl J., Lebert-Ghali C.E., Vacher J., Mayotte N., Sauvageau G. Evidence for Hox and E2A-PBX1 collaboration in mouse T-cell leukemia. Oncogene. 2008. Aug 4.

Complete list of Dr Bijl’s publications (PubMed)

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DISTINCTIONS AND ACHIEVEMENTS

• Development of the first and only mouse model for B-cell leukemia induced by the E2a-PBX1 oncogene.
• MRC Postdoctoral Fellowship.

ADDITIONAL INFORMATION

Collaborations

The lab started in fall 2006 and is very young and dynamic. Imbedded in the axe Immuno-onco-hematology of the Research Center Hopital Maisonneuve-Rosemont there are active collaborations with the lab of Drs. Roy and Labrecque on the effect of Hoxb4 on expansion of leukemic stem cells and memory T-cells, respectively. Results on the expansion of leukemic stem cells are extremely important for the potential use of Hoxb4 in stem cell therapy, while expansion of memory T cells by Hoxb4 is not only important for an immunotherapy application, but will provide an accessible model to study the molecular pathway of self-renewal divisions induced by Hoxb4. 

There is also a full collaboration established with Dr. Affar regarding the isolation of HOX and fusion oncogene protein complexes to identify new partners. Potential oncogenic properties of newly identified protein partners might open the way to new targets for drug strategies.

Outside Canada we have a long-lasting collaboration with Dr. Alex Thompson (Queens’ University, Belfast, UK) on the role of several HoxA genes and their co-factor Meis1 in myeloid leukemia.
Students in the lab will get a thorough formation in hematopoietic stem cell and leukemia biology. They will learn to exploit different genetic mouse models, such as knock-outs, transgenics and BM chimeras to study the function of our genes of interest. Evaluation of these models includes expression analysis by Q-RT-PCR, Northern and Western Blotting, clonal analysis using Southern blotting, and hematopoietic analysis using several in vitro culture and transplantation assays etc.

Student Training Program

Students of the laboratory receive full training on the biology of leukemia and hematopoietic stem cells. They learn to use a variety of genetically-modified mouse models to study different gene functions of interest such as: knockout, transgenic and BM chimera. The evaluation of these models include: analyses of expression through Q-RT-PCR, and Northern and Western blots; clonal analyses through Southern blots; and hematopoietic analyses through different in vitro cultures and transplantation trials.

Grants

• HMR Foundation (startup grant )
• Canadian Cancer Society
• Leukemia & Lymphoma Society
• NSERC

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