Congratulations to all the Lymphoma Canada Research Fellowship award winners!
2016-2018 Lymphoma Canada Research Fellowship
2016 Lymphoma Canada Research Fellowship has been awarded to Dr. Anja Mottok, a hematopathologist and research fellow at the British Columbia Cancer Agency.
Title: Deciphering the cellular crosstalk in the tumour microenvironment of Hodgkin lymphoma.
Classical Hodgkin lymphoma (cHL) is the most prevalent type of lymphoma affecting people under the age of 30. Despite the fact that most patients can be cured with chemotherapy, 30% still experience relapse and eventually succumb to their disease. There is now increasing evidence that not only tumour cells, but also the normal cells surrounding them (the “microenvironment”), are important for tumour progression. Over the past years a number of studies have contributed to the current knowledge about the mechanisms by which the tumour cells in cHL, the Hodgkin and Reed-Sternberg (HRS) cells, recruit immune cells to form the tumour microenvironment and manipulate them to be non-functional.
Dr. Mottok’s experimental program aims to identify and characterize genetic changes and molecular pathways that provide the rationale for targeting tumour microenvironment biology as a therapeutic approach. The goal of her proposed research project is to comprehensively characterize the composition of the tumour microenvironment in cHL and explore which genetic changes in the tumour cells might have an impact on microenvironment composition. Integration of these results will provide the unique opportunity to relate mutational composition of the tumour cells to the immune cell composition. By establishing a linkage between genomic alterations, microenvironment composition and clinical outcome, this research has the potential to lead to identification of novel biomarkers and their use in clinical practice.
Link to Dr. Mottok’s Pubmed publications
2015-2017 Lymphoma Canada Research Fellowship
2015 Lymphoma Canada Research Fellowship has been awarded to Dr. Kerry Savage, a medical oncologist and researcher at the British Columbia Cancer Agency.
Title: Gene expression profiling of peripheral T-cell lymphomas
With poor survival rates in PTCLs, there is an urgent unmet need for novel drug design based on an understanding of the critical genes and pathways that operate in malignant T cells. Currently, oncogenic drivers in PTCLs and their functional significance are poorly understood. Dr. Savage’s innovative experimental design has the capacity to elucidate the unknown molecular and cellular biology underlying these diseases, thereby providing the scientific basis for novel drug design.
Update – September, 2016
Dr. Savage reports…Previous studies using gene expression profiling (GEP) have been hampered by the use of whole lymph node biopsy specimens containing both malignant T cells as well as non-malignant cells. This results in a mixed genetic signature from malignant and non-malignant cells. The British Columbia Cancer Agency (BCCA) collected a precious tumour bank of frozen diagnostic lymph node cell suspensions over the past 20 years for research purposes. The aim of our project was to obtain pure or highly enriched tumour to interrogate the malignant T cells themselves. In the past 12 months we have made considerable progress in our experimental aims. Using all available T cell lymphoma samples in the BCCA tumour bank, we implemented a plan to identify and purify the malignant T cells using a cell sorter. We then used additional molecular tests to prove those cells were malignant. We have performed sequencing of the RNA (called RNA-seq) to identify the genes that are important for tumour proliferation and survival. We are in the process of analysing the gene-expression data in the two most common types of T-cell lymphoma: peripheral T-cell lymphoma not-otherwise specified (PTCL NOS) and angioimmunoblastic T cell lymphoma (AITL).
Link to Dr. Savage’s Pubmed publications
2013-2015 Lymphoma Canada Research Fellowship
2013 Lymphoma Canada Research Fellowship has been awarded to McGill University Professor Jerry Pelletier.
Title: Validating Tumor Suppressor Genes in Burkitt Lymphoma
Update – May, 2015
Dr. Pelletier reports… “Burkitt’s lymphoma (BL) is a type of non-Hodgkin lymphoma. It is characterized by a mutation in a gene called myc, which triggers the BL cells to grow uncontrollably. However, much is still unknown about the cause of the disease. Genetic studies of BL tumours have identified a number of genes that are mutated in these tumours. The goal of our research is to determine whether these mutated genes play a role in the development of BL.”
“In order to determine the role of the identified mutated genes, we used a mouse model of Burkitt’s lymphoma to screen each gene. These mice normally develop lymphoma due to a mutation in the myc gene. Blood stem cells can be manipulated to include one of the mutated genes and then transplanted into the mice to repopulate their immune system. If the gene mutation contributes to tumour formation, B-cell lymphomas develop more quickly than usual. If the mutation has no effect on tumour growth, B-cell lymphomas will develop at the normal rate.”
“To introduce the desired gene mutations with precision we used a specialized genetic engineering tool. 91 genes that were identified from the BL genetic screening experiments were introduced into Burkitt lymphoma cells. These cells were then transplanted into mice and the time until the onset of lymphoma was monitored. The first round of experiments has been completed and we have identified genetic mutations that accelerate tumour development. Current work is directed at confirming our results and then characterizing the function of these genes. We will then conduct further experiments to identify how these genes contribute to tumour growth. Our hope is that these studies will illuminate the molecular processes involved in BL, potentially leading to future development of more effective and less toxic therapies.”
Link to Dr. Pelletier’s Pubmed publications
2011-2013 Lymphoma Canada Research Fellowship
2011 Lymphoma Canada Research Fellowship has been awarded to Dr. Julie Nielsen and her supervisor Dr. Brad Nelson of the Trev and Joyce Deeley Research Centre, BC Cancer Agency.
Title: The Mutated Lymphoma Genome: A Target for Immune Surveillance and Immunotherapy
Cancer is caused by genetic mutations that provide cells with abnormal growth properties. It is now possible to identify these mutations using “next-generation” DNA sequencing technology, but an important clinical challenge is how to therapeutically target mutations in patients. We and others have shown that T cells of the immune system can recognize tumour mutations as “foreign” and mount an immune attack. The goal of this project is to develop efficient methods to analyze and enhance the T cell response to common mutations found in lymphoma. Our long-term goal is to develop personalized cancer vaccines that harness the power of the immune system to treat lymphoma.
Link to Dr. Nelson’s Pubmed publications
Link to Dr. Nielsen’s Pubmed publications
2008-2010 Lymphoma Canada Research Fellowship
The Philip Lavorgna LC Research Fellowship Award was granted to Dr. Stuart A. Berger of University Health Network, Toronto General Research Institute.
Title: c-Myc-dependent targeting of lymphoma in vitro and in vivo
Lymphomas often involve the c-myc oncogene. It was found that inhibiting an enzyme called calpain causes c-myc-transformed cells, but not normal cells to die. The goals are to evaluate how c-myc sensitizes human lymphoma cells to calpain inhibition and to optimize its use in a lymphoma model. This project will provide information on the function and potential of calpain as a lymphoma target
Link to Dr. Berger’s Pubmed publications
The Terry Creighton LC Research Fellowship Award was granted to Dr. Philip Hieter of Michael Smith Laboratories, University of British Columbia.
Title: Understanding and exploiting chromosome instability associated with NHL for the discovery of broad spectrum therapeutics.
Understanding and exploiting chromosome instability associated with NHL for the discovery of broad spectrum therapeutics. This research is significant both in the context of understanding the basic biology of chromosome instability underlying the onset of NHL, and the potential to identify novel therapeutic targets and drugs that could dramatically improve the quality of life and treatment of NHL.
2007-2009 Lymphoma Canada Research Fellowship
Dr. Xiaoyan Jiang, Terry Fox Laboratory, BC Cancer Agency, “Molecular and Functional Characterization of a Novel Oncogene (AHI-1) in Human Cutaneous T-Cell Lymphomas.”
Because many forms of human lymphoma originate in blood stem cells, uncovering the changes that occur in these cells is crucial to understanding how these diseases develop and progress. This study is focused on investigating a newly discovered oncogene (cancer causing gene), AHI-1 that was recently identified. AHI-1 is involved in murine lymphoma development (lymphoma in mice) and shows abnormal expression in human blood cancer cells, including Sezary cancer cells from patients with cutaneous T-cell lymphoma and leukemic stem cells from patients with chronic myeloid leukemia. These findings are highly intriguing indicators that AHI-1 is likely to be an important new cancer causing gene involved in development of lymphomas and leukemia in humans. The investigations should help to identify critical target genes that interact with AHI-1 and play crucial roles in altering T-cell signaling pathways involved in processes of human T-cell lymphoma development. This investigation is expected to translate into new diagnostic and treatment strategies leading to the development of targeted cancer treatment that will be more effective and have fewer side effects than currently used chemotherapy.
Link to Dr. Jiang’s Pubmed publications
Dr. Alberto Martin, University of Toronto, “Characterizing the Biochemical Mechanism of Somatic Hypermutation”
The immune system plays a major role in protecting humans from bacteria, viruses and toxins. One of the ways that the immune system accomplishes this is by producing antibodies that bind to and neutralize these pathogens. B cells produce antibodies and can increase the binding strength of the antibody to the specific pathogen by making changes (i.e. mutations) in the antibody genes. This process is termed somatic hypermutation and is initiated by an enzyme called activation-induced cytidine deaminase (AID). Although AID mutates antibody genes, this enzyme sometimes makes mistakes and mutates other genes. Unfortunately, some of these other genes can cause cancer if mutated. Three types of lymphomas might be caused by mistake made by the AID enzyme, namely Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Burkitt’s lymphomas. The overall goal of this research is to determine how the AID enzyme produces mutations in antibody genes as well as in other genes with the goal to gain further insight into AID’s oncogenic potential.
Link to Dr. Martin’s Pubmed publications
2004-2006 Lymphoma Canada Research Fellowship
Lymphoma Canada/RBC Dominion Securities Inc. Research Fellowship was awarded to Dr. Andrew Weng, BCCA, Cancer Research Centre for his study in “Downstream Targets of Notch in Lymphoid Neoplasia”.
“A common theme in cancer is the dysregulation of a normal development process that either directly causes cells to grow in an uncontrolled manner, or renders them susceptible to other deleterious changes that, in turn, lead to uncontrolled growth. One example of this situation occurs with a gene called Notch, which is important for guiding the development of normal lymphoid cells that help the body to fight infection. We recently discovered that the Notch gene is mutated in over 50% of cases of a pediatric and adult lymphoproliferative disorder, T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia. The Notch mutations we identified lead to inappropriate activation of several other genes, and thus, these “downstream” genes are actually responsible for enacting the cancer program and causing uncontrolled tumour growth. We intend to study these downstream genes to determine the molecular mechanism by which they promote malignant transformation of normal lymphoid cells and drive the growth of established lymphoid tumour cells. Furthermore, since the Notch signaling pathway is so highly conserved in the immune system, we anticipate these downstream genes will also be relevant in the pathogenesis of other types of lymphoma. By identifying the molecular pathways most critical to lymphoid tumour development/growth, we will be able to design more effective and less toxic therapies for lymphoproliferative disorders.”
Link to Dr. Weng’s Pubmed publications
2006 Lymphoma Canada Research Fellowship was awarded to Dr. Raymond Lai, University of Alberta, Edmonton Alberta; “Role of STAT3 activation in Mantle Cell lymphoma”.
“Mantle Cell lymphoma is an aggressive lymphoma for which conventional therapy is ineffective in most cases. Based on the previous data, they believe that a cancer-causing gene, STAT3, may contribute to the formation of a subset of MCL by promoting cell growth and survival advantage. To determine the importance of STAT3 in MCL, they will investigate a large number of MCL patient tumour samples, to establish if STAT3 in MCL is associated with other biological or clinical markers. Second, the will employ several cell culture experimental models in which the biological activity of STAT3 can be experimentally modulated, to determine if STAT3 inhibition is a feasible treatment approach for MCL patients.”
Link to Dr. Lai’s Pubmed publications
2005 Lymphoma Canada Research Fellowship was awarded to Dr. Tony Reiman, Cross Cancer Institute for his study of The Centrosome as a Therapeutic Target in Multiple Myeloma
Multiple Myeloma is an incurable lymphoproliferative cancer for which new treatment approaches are needed. The centrosome is an important structure in human cells that controls cell division, and other processes. We have discovered that the centrosome and some proteins in the centrosome are altered in multiple myeloma cancer cells, in a way that correlates with poor patient outcomes. With this fellowship we will study further the components of the centrosome that are altered in myeloma, with great emphasis on finding ways to exploit these alterations for the purposes of developing new therapeutic strategies. There is potential for this work to lead to clinical trials of new drug treatments for myeloma in short order.
Dr. Tony Reiman reports… “to summarize: 1) We have seen expression of Aurora family kinases at varying levels of primary myeloma cells from patients with the disease. 2) We have found that Aurora A kinase gene knockdown by RNA interference induces apoptosis and reduces visibility of myeloma cell lines. 3) We have found that two different chemical, small molecule Aurora kinase inhibitors also have cell killing effects in a panel of myeloma cell lines, inducing the expected polyploid phnotype prior to cell death. 4) We have found that the chemical inhibitors also reduce the viability of purified myeloma bone marrow plasma cells provided by a patient with the disease. 5) We have studied the combination of the chemical inhibitors with the conventional myeloma therapies, and found in both cell lines and primary cells that the inhibitors seem to have additive effects of the two classes of therapy. 6) We have made arrangements to obtain other Aurora kinase inhibitors for pre-clinical evaluation, as well as other inhibitors of centrosome proteins. 7) We are preparing to initiate studies of myeloma treatment with Aurora kinase inhibitors in murine myeloma xenograft models.”
These results have been submitted for presentation at the 2006 meeting of the American Society of Hematology and will also be submitted for publication in a peer-review journal.
Link to Dr. Reiman’s Pubmed publications
2005 Lymphoma Canada/Hoffman-La Roche Research Fellowship was awarded to Dr. John Decoteau, Royal University Hospital
Title: Epigenetic Silencing of Putative Tumour Suppressor Gene PRDM1 in human DLBCL
Link to Dr. Decoteau’s Pubmed publications
2004 Lymphoma Canada/Deborah Sterritt Research Fellowship was awarded to Drs. John Bell and Harold Atkins – Ottawa Regional Cancer Centre, Ottawa Hospital
Normal cells lose their protection against viral attack as they become more malignant. Exploiting this weakness has allowed researchers to develop a strategy using certain viruses to selectively infect and kill many types of cancer cells. Drs. Bell and Atkins aim to expand their knowledge of which viruses are the most active in killing lymphoma cells and to address the reasons, at a genetic level, of why some lymphomas are sensitive to viral attack and others are not.
Link to Dr. Bell’s Pubmed publications
2004 Lymphoma Canada/GlaxoSmithKline Research Fellowship was awarded to Dr. Yaacov Ben-David – Sunnybrook & Women’s College Health Science Centre
Dr. Ben-David’s study is the continuation of ongoing research and the goals of this study will provide important insight into the molecular mechanisms of B-lymphoproliferative disorder in humans as well as gaining insight into the roles of the Fli-1 gene in lymphoproliferative diseases towards clinical treatment.
Link to Dr. Ben-David’s Pubmed publications
2001-2003 Lymphoma Canada Research Fellowship
2003 Lymphoma Canada/Berlex Canada Research Fellowship was awarded to Dr. Diponkar Banerjee – British Columbia Cancer Agency
The fellow will determine the patterns of gene expression in tumour cell lines exposed to antibodies that recognize novel cell surface markers (year 1). As well, the research will determine whether the genes encoding the proteins are amplified or mutated in Hodgkin’s and Non Hodgkin’s Lymphoma (year 2) and whether expression of the gene or protein in archived biopsies influence outcome.
Link to Dr. Banerjee’s Pubmed publications
2003 Lymphoma Canada Research Fellowship was awarded to Dr. Lawrence Panacsi – Lady Davis Institute for Medical Research – Montréal
Link to Dr. Panacsi’s Pubmed publications
2001 Patricia Manson Memorial Research Fellowship was awarded to Dr. Steven Ralph for his research on using genomic approaches to better understand genetic alterations underlying lymphoma development and progression.
Link to Dr. Ralph’s Pubmed publications
2001 Shaw Lymphoma Research Fellowship was awarded to Dr. Albert Kabore for his research to determine if TRAIL (tumour necrosis factor related apoptosis inducing ligand) can kill lymphoma cells by itself or if it can boost the effectiveness of standard chemotherapy drugs.
Link to Dr. Kabore’s Pubmed publications
1998 – 2000 Lymphoma Canada Research Fellowship
1999 Patricia Manson Memorial Research Fellowship was awarded to Dr. Steven Robert Knezevich who researched the identification of genes involved in clonal evolution of follicular lymphoma.
Link to Dr. Knezevich’s Pubmed publications