A Terry Fox New Frontiers Program Project Grant: Exploiting Pathogenic Mechanisms in Acute Leukemia for Clinical Translation
The overall long-term goal of this program is to better understand the difference between normal blood-forming cells and leukemic cells, and thereby to identify and exploit vulnerable disease-causing pathways that may be shared across different types of acute leukemias that can then be translated into useful biomarkers and treatments that are more effective and less toxic.
| Project Leaders | Aly Karsan , Connie Eaves , Martin Hirst , Andrew Weng |
|---|---|
| Project Co-Investigators | Keith Humphries , Peter Lansdorp , Gregg Morin , Raewyn Broady |
| Project Contacts |
For all project related inquires contact: Joanne JohnsonAmy Yu |
| Involved Organizations | |
| Funding Agencies |
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Overview
Our research team: scientists, clinicians, research staff, trainees, and project managers.
Acute leukemias remain one of the most devastating and costly cancers with less than 1 in 5 adult patients surviving 10 years and some childhood patients failing current treatments. Even in those who survive, consequences of the toxic treatments diminishes lifespan and the quality of life. While the need for improved treatment is great, so too is the challenge. We recognize the enormous complexity of both the normal blood forming system and the diversity of ways in which acute leukemia can arise and progress, with many important contributions having come from this longstanding program in acute leukemia research. There is thus a critical need for new approaches for investigating mechanisms of disease pathogenesis and new models to help translate basic findings into new and improved treatments that effectively target leukemic cells while sparing normal blood forming cells. This now seems within reach with the advent of modern tools that can identify every change in every gene in cells, and that can also determine whether and why every gene is being expressed. In addition, vast libraries of naturally occurring and synthetic chemicals that can target specific molecules in cells are now available. Our group brings powerful genetic engineering tools to enable human models of aggressive leukemia to be rapidly created in the lab so that mechanisms of treatment resistance and new drugs and biomarkers can be efficiently analyzed and tested directly and repeatedly in human cells that mimic patients’ cells. We have also developed mouse models that allow us to grow patient leukemic cells in mice that efficiently accept human cells.
The overall long-term goal of this acute leukemia program is to better understand the difference between normal blood-forming cells and leukemic cells and thereby to identify and exploit vulnerable disease-causing pathways that may be shared across different types of acute leukemias that can then be translated into useful biomarkers and treatments that are more effective and less toxic.
Four projects and two supporting cores, providing key technical support, are proposed that will focus on examples of the worst types of leukemia known, develop human models of these and, in concert with world experts in the field, we will use these models to search for common therapeutic targets. Success will be facilitated by a strong history of interaction between the applicants complemented by collaborating scientists outside the funded team, the participation of 2 clinician-scientists, a close relationship with the Leukemia/BMT Program at BC Cancer, and the involvement of an outstanding group of trainees.
Project 1 | Connie Eaves |  |
Analysis and Control of Normal Human CD34+ Hematopoietic Cell States |
|---|---|---|---|
Project 2 |
Aly Karsan | |
A New Targetable Pathway in Adult Human AML involving and SCF Complex |
Project 3 |
Andrew Weng | |
Deciphering Mechanisms of Human T-cell transformation by synthetic design |
Project 4 |
Martin Hirst | |
Aberrant Epigenetic Pathways as Novel Targets in Human AML |
Core 1 |
Connie Eaves |  |
Primary Cell Accrual, manipulation, tracking and testing |
Core 2 |
Martin Hirst | |
Molecular Characterization tools, protocols and bioinformatics |
Contact Information
For all project related inquiries please contact:
Joanne Johnson, Project Manager
Genome Sciences Centre, BC Cancer Agency
Email: jjohnson@bcgsc.ca
or
Amy Yu , Project Manager
Terry Fox Laboratory, BC Cancer Agency
Email: ayu@bccrc.ca