Dr. Aly Karsan
My lab focuses on two major areas in normal and malignant blood cell formation: (1) Understanding the molecular basis of myeloid malignancies, such as the preleukemic bone marrow failure condition called myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML); and (2) Determining the role of the endothelium in the development of the hematopoietic system.
With respect to the myeloid malignancies, we have a major focus on understanding the relationship of non-coding RNAs and the regulation of the epigenome. We have taken genomic approaches to study patient material followed by functional analyses of specific microRNAs. One example of translation of genomic studies to understanding biologic function is our discovery that microRNAs residing on the long arm of chromosome 5 act to independently regulate innate immune signaling and DNA methylation. Deletion of chromosome arm 5q is the commonest structural anomaly seen in MDS, and current studies centre around establishing the function of these microRNAs, deregulated innate immune signaling and remodeling of the epigenome in the manifestations of MDS.
We have also identified specific defects in the ubiquitin pathway in AML that are potentially tied to regulation of the epigenome, and we are using proteomic, genomic and in vivo methods to define the role of this pathway in leukemogenesis and hematopoietic stem cell function. We are using a variety of in vivo transplantation assays, in vitro cell biology and cell signaling studies as well as additional genomic approaches to answer these questions.
Lab website: http://www.bcgsc.ca/faculty/dr-aly-karsan-md
Dr. Wan Lam
Dr. Lam’s laboratory at the BC Cancer Research Centre is known for multi-dimensional approaches to develop combinatorial detection and treatment strategies. His team has developed whole-genome technologies and bioinformatic tools for tracking genetic, epigenetic, and gene expression events in order to identify genes and pathways critical to cancer progression and treatment responses. His research team focuses on (1) the biology of lung cancer and COPD in smokers and non-smokers, (2) molecular mechanisms of environmental carcinogenesis, (3) the involvement of developmental genes in cancer, (4) immune cells in the tumour microenvironment, and (5) the genetic basis of aggressiveness, metastasis, and treatment response.
Lab website: https://www.bccrc.ca/dept/io/people/wan-lam
Dr. William Lockwood
Lung cancer is the leading cause of cancer mortality worldwide, suffering from a late stage of disease at the time of diagnosis and a paucity of effective therapeutic strategies to treat advanced tumours. However, with our increasing understanding of lung cancer biology has come the advent of targeted therapies to combat this devastating disease. These therapies target mutated components of key cellular pathways on which tumours have become dependent on for survival, yielding drastic initial response rates without the major side effects of traditional chemotherapies. Despite these successes two major problems remain: first, the majority of lung cancer patients have tumours without mutations in targetable genes and; second, all patients eventually develop resistance to treatment with these targeted agents. In addition, since lung tumours commonly have hundreds of mutated genes, it is difficult to pinpoint those that are responsible for tumour growth and resistance to therapy, creating a clear bottleneck in the translation of laboratory findings to a clinical setting.
My lab utilizes an integrative strategy to address these issues. Through analysis of the genomic profiles of human lung tumours, we aim to identify novel genes and pathways that are altered during lung cancer development. Furthermore, by combining this information with the characterization of mice genetically engineered to develop lung tumours, we attempt to elucidate the key genes driving lung cancer initiation, progression and response to therapy. Lastly, by screening libraries of chemical compounds across lung cancer cells, we aim to characterize novel inhibitors of these identified genes and their corresponding pathways that show promise for use as targeted therapies. Together, this work will further our understanding of lung cancer biology and create insight toward the development of new approaches to diagnose and treat patients suffering from this disease.
Lab website: https://www.bccrc.ca/dept/io/people/william-lockwood
Dr. Marco Marra
I am Professor and Head of Medical Genetics at UBC; UBC Canada Research Chair in Genome Science and the Director of the BC Cancer Agency Genome Sciences Centre (GSC). I was trained as a geneticist, and have been involved in the development and application of high-throughput genomics strategies, with special emphasis on large-scale DNA sequencing and bioinformatics. I have spent much of my career working within and leading teams to conduct large-scale high throughput genomics projects.
A current focus of my research activities is the development and application of “next generation” sequencing approaches to characterize cancer genomes, transcriptomes and epigenomes, with the aim of comprehensive identification of the genetic and epigenetic changes that drive cancer progression. With such data, and as co-Leader of the BC Cancer Agency Personalized Oncogenomics Project (http://www.cbc.ca/natureofthings/episodes/cracking-cancer), my objective is a new generation of diagnostic, prognostic and treatment strategies to benefit cancer patients.
A second focus of my research revolves around the functional interplay between cancer genomes and epigenomes. My team has described the strikingly high frequency of mutations in transcriptional regulators, including chromatin modifiers, implying they are “cancer genes” and that mutations in them drive cancers. The interplay between the genome and the epigenome is thus exploited by cancer cells, but exactly how, the extent to which common mechanisms exist across cancers and whether answers to such questions might reveal therapeutic opportunities all require investigation. My team is analyzing the cancer regulatory networks impacted by epigenome dysregulation using cell biology, genetics, genomics, bioinformatics and functional genomics tools, and we aim to understand the selective advantages conferred to cancer cells as a consequence of such dysregulation. My objectives are to: (1) Identify and characterize regulatory networks disrupted by epigenome dysreulation in cancer; (2) Assess the extent to which epigenome dysregulation converges on common pathways/networks in different malignancies; (3) Identify candidate therapeutic vulnerabilities resulting from epigenome dysregulation.
Lab website: http://www.bcgsc.ca/faculty/mmarra