Interdisciplinary
Oncology Program
Tumour Biology and Immunology
Dr. Kevin Bennewith
Dr. Kevin Bennewith obtained his PhD in Pathology and Laboratory Medicine at UBC in 2004 studying solid tumour physiology with particular emphasis on quantifying poorly oxygenated (hypoxic) tumour cells. He then joined the laboratory of Dr. Amato Giaccia at Stanford University as a post-doctoral scholar, where he was involved in several projects investigating the role of hypoxia-induced secreted proteins in the growth and metastasis of solid tumours. His post-doctoral work included studying the role of connective tissue growth factor in pancreatic tumour growth and using an orthotopic pancreatic tumour model to study the efficacy of chemotherapeutics designed to target hypoxic tumour cells. He also helped to discover a central role for lysyl oxidase in breast cancer metastasis through promoting the recruitment of bone marrow-derived cells to metastatic target organs. Dr. Bennewith’s current research program at the BC Cancer Agency involves studying how hypoxic tumour cells promote tumour metastasis, how tumour secreted cytokines promote the recruitment of immune suppressive myeloid and lymphoid cells to various tissues, and the influence of these immune suppressive cells on primary and metastatic tumour growth. Dr. Bennewith’s research has been funded by the Terry Fox Foundation, the Canadian Institutes of Health Research, the BC Cancer Foundation, the Cancer Research Society, and a Michael Smith Foundation for Health Research Career Investigator Award. Dr. Bennewith is currently a Senior Scientist at the BC Cancer Agency and an Associate Professor in Pathology and Laboratory Medicine at UBC.
Admin Email: cclugston@bccancer.bc.ca
Dr. Michael Cox
Dr. Cox’s research is funded by the Terry Fox Foundation, Canadian Cancer Society, the VGH & UBC Hospital Foundation and the Prostate Cancer Foundation of British Columbia. His work focuses on early genetic changes in prostate cells, how resulting tumor cells respond to growth factors in the presence or absence of testosterone and how these cellular changes allow prostate tumor cells to utilize these growth factors to aid development of testosterone independence. With colleagues at the Vancouver Prostate Centre and University of British Columbia, he is developing combinatorial antisense and small molecule drug strategies that decrease the responsiveness of tumor cells to growth factors and has shown that prostate cancer cells treated in this way are more sensitive to testosterone deprivation or treatment with other chemotherapies. These are first steps in developing effective treatments for patients with advanced prostate cancer.
Dr. Mads Daugaard
Genomics and Computational Biology, Tumour Biology and Immunology, Molecular Biology and Metabolism
Dr. Mads Daugaard is a molecular biologist specialized in pre-clinical and translational cancer research. He earned his PhD degree in 2007 from the Faculty of Health Sciences, University of Copenhagen, for his studies on heat shock proteins in relation to cancer cell survival mechanisms. After completing his PhD, Dr. Daugaard received a junior fellowship award to continue his work at the Danish Cancer Society Research Centre on stress signaling pathways related to DNA damage response mechanisms. In 2010, Dr. Daugaard received a research award from the Danish Cancer Society to do postdoctoral training in molecular pathology at the BC Cancer Research Centre and the Department of Pathology and Laboratory Medicine, University of British Columbia (UBC).
In 2014, Dr. Daugaard was recruited to the Vancouver Prostate Centre as a Senior Research Scientist and a faculty member of the Department of Urological Sciences at UBC. His ongoing research focuses on molecular and biochemical events underlying sugar-modifications of proteins in solid tumors, chromatin context-dependent DNA repair mechanisms, chemotherapy resistance mechanisms, and immune-evasion mechanisms in cancer.
Dr. Daugaard has published original research in top-tier scientific journals and received competitive national and international research funding support from institutions such as the US Department of Defense (DoD), the National Cancer Institutes (NIH), the Canadian Institutes of Health Research (CIHR), the Stand Up 2 Cancer (SU2C) initiative, the St. Baldrick’s Foundation (SBF), and Vancouver Coastal Health Research Institutes (VCHRI). Dr. Daugaard was honoured with the Prostate Cancer Canada Rising Star Award in 2014 and the Robert J. Arceci Innovation Award in 2019.
Dr. Daugaard is a biotech entrepreneur and a co-founder of the biotech companies VAR2 Pharmaceuticals (2012), VarCT Diagnostics (2017), Rakovina Therapeutics (2020), and SnapCyte Solutions (2022).
Dr. Shoukat Dedhar
The Dedhar lab carries out research in the broad area of the Tumour Microenvironment.
Specifically, the goals are to understand how tumour cells communicate with the extracellular microenvironment: matrix proteins, growth factors and other cell types, and to understand, at the molecular and cellular level, how these interactions promote tumour growth and metastasis.
The goals are to identify key signaling pathways and proteins that promote tumour progression and to develop novel therapeutic approaches to target these pathways and proteins to suppress tumour growth and metastasis.
Admin Email: jhunter@bccancer.bc.ca
Dr. Xuesen Dong
Dr. Dong’s laboratory investigates the molecular mechanism by which prostate tumors develop therapy resistance with emphasis on RNA binding proteins that promote treatment-resistant disease progression. His lab applies computer-aided drug design to develop new anti-cancer drugs and RNA sequencing technology to explore cell-free circular RNA as diagnostic markers.
Dr. Connie Eaves
Experiments in this laboratory and elsewhere have established the existence in adults (both mouse and man) of primitive hematopoietic stem cells capable of permanently reconstituting the production of mature blood cells in marrow-ablated or suppressed recipients. A major part of our work continues to focus on the development, validation and use of quantitative assays that are specific for biologically distinct subsets of these stem cells using syngeneic (mouse-mouse) and xenogeneic (human-mouse) hosts. We have also identified a developmental “switch” that alters stem cell proliferation and self-renewal control in the post-natal period. We are now trying to elucidate the molecular mechanisms underlying each of these causes of variable stem cell behavior using defined culture systems, gene transfer strategies, and genome-wide gene expression analyses. We have pioneered the development of quantitative assays for normal mouse and human breast epithelial stem cells and these are being used to identify their distinguishing features and growth regulation. Studies to adapt these methods for application to human breast cancer are underway. The objective is to provide a basis for analyzing molecular and genetic determinants of breast cancer at the level of the breast cancer stem cell and thereby develop more rational, patient-targeted therapies.
Admin Email: atoner@bccrc.ca
Dr. Cathie Garnis
Our primary research interests are focused around head and neck malignancies. These are a group of biologically similar tumors originating from tissue of the upper aerodigestive tract, including the lip, oral cavity (mouth), nasal passages, paranasal sinuses, oropharynx, and larynx. More than 4,300 Canadians will be diagnosed with this type of cancer this year and approximately 1,600 of them will die from it.
Currently, histopathological criteria are the gold standard for grading and classifying many tumor types. In recent years it has become clear that cancers with very similar morphologies may have drastically different underlying gene changes. Given that cancer is a disease driven by accumulated gene changes, it is imperative that we determine which of these changes are associated with specific clinical parameters. This will ultimately give us insight into mechanisms driving observed clinical behaviors (chemoresistance, metastasis, etc.) and provide us with effective biomarkers for guiding treatment strategies.
At the Garnis Lab, we are using molecular profiles of head and neck malignancies to better understand the gene changes involved in initiation and progression of this disease. We are looking into dysregulation of the genome and transcriptome (including non-coding RNAs) to develop molecular stratifications for what is presently treated as a homogeneous disease.
In addition to analyzing tumor tissues, we are investigating the utility of surface epithelial markers and blood-based biomarkers for managing disease. Surface epithelial markers may arise due to malignancy-associated changes (MACs) in normal tissues and may be useful for detecting disease when tumors arise in inaccessible locations, such as tonsillar crypts, which is common in the oropharynx.
Admin Email: cclugston@bccancer.bc.ca
Dr. Alina Gerrie
Dr. Alina Gerrie is a hematologist and Assistant Professor in the Divisions of Hematology and Medical Oncology at the University of British Columbia (UBC) and a Clinician Investigator at the Centre for Lymphoid Cancer at BC Cancer. Dr. Gerrie is involved in translational, clinical trial and outcomes-based research related to leukemia and lymphoma. Other academic interests include the investigation of novel therapeutics and stem cell transplant for chronic lymphocytic leukemia (CLL) and lymphoma and improving long-term outcomes for lymphoma and stem cell transplant survivors. Dr. Gerrie currently holds a Michael Smith Health Research Investigator Award and grant funding through the Mitacs Accelerate Program and Cancer Research Society to investigate the impact of genetic abnormalities on population-level outcomes in chronic lymphocytic leukemia (CLL) patients. She is a co-investigator on a Genome Canada Large-Scale Applied Research Project (LSARP) to advance personalized treatments of lymphoid cancer patients in collaboration with Drs. Christian Steidl and David Scott, and is a collaborator on a number of CIHR grants and industry-sponsored clinical trials.
Dr. Kevin Hay
My research focuses on preclinical development, bench-to-bedside translation, and clinical evaluation of novel cellular immunotherapeutic approaches, with an expertise in chimeric antigen receptor (CAR-)T cell therapy.
A CAR is comprised of an extracellular antigen recognition domain linked to intracellular T cell signaling domains, which after introduction into the T cell enables T cell activation upon encounter with the target antigen. Clinical trials of CAR-T cells targeting CD19 have demonstrated impressive results in the treatment of patients with relapsed/refractory B-cell malignancies such acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia (CLL), with response rate >80% for some cancers, highlighting the promise and feasibility of this cellular therapeutic approach.
My laboratory aims to: (a) develop CAR-T cells targeting other malignancies, such as myeloma, and (b) modify CAR-T cells so as to improve efficacy and decrease toxicity. We are exploring multi-antigen targeting approaches, modifications to the CAR construct, and different approaches to T cell manufacturing.
My clinical research with the Leukemia/BMT Program of BC focuses on the development of a CAR-T program in BC and involvement in clinical trials of CAR-T cell therapy.
Dr. Rob Holt
The Holt Lab uses cutting edge tools and methodologies to investigate the biology of cancer from several different angles. Focusing on the immune system, the group has used deep sequencing to survey T cell repertoire diversity at the resolution of individual clonotypes and are now using these methodologies to explore the role of T cells in cancer. They are also working to develop cancer immunotherapies using engineered T cells to selectively deliver cytotoxic payloads to bolster the anti-cancer immune response and to enhance tumour cell killing. The group employs their expertise in DNA sequencing and computational analyses to investigate the role of infectious agents in cancer development and were the first to demonstrate a strong link between the pathogen Fusobacterium nucleatum and colorectal cancer. Finally, they apply deep sequencing technologies to identify the spectrum of mutations in various cancer types, with a particular focus on tumour evolution and the identification of antigens for cancer vaccines.
Dr. Xiaoyan Jiang
The overall goal of Dr. Jiang's research program is to understand the molecular mechanisms and cellular functions of specific oncogenes, tumor suppressor genes, miRNAs/target genes, and their associated pathways/networks, in the regulation of the properties of cancer/leukemic stem cells, signal transduction events, metabolism/mitochondria vulnerabilities, immune responses and initiation and progression of human leukemia and drug resistance. The ultimate objective is to identify and characterize key druggable molecules and pathways, using our well-established in vitro and patient-derived xenotransplantation (PDX) models, which will lead to new, rationally designed, more effective, and less toxic, personalized anti-cancer therapies. In particular, Dr. Jiang and her lab are extremely interested in developing mechanism-based combination therapeutic strategies that can directly target drug-insensitive leukemic stem cells and mutated drug-resistant cells, to improve outcomes in leukemia patients, especially those destined to develop drug resistance.
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.
Dr. Ramon Klein Geltink
Our team aims to better understand the role of metabolism in regulation of immune cell function. We aim to expand our understanding of the role of metabolism in the dysfunction of immune cells in cancer, and to uncover therapeutic targets to improve cancer immunotherapy. When cells are confronted with changing environments they have to adapt to their new surroundings to maintain cellular function. This adaptation is especially relevant for immune cells that move throughout the body and encounter different levels of metabolites and nutrients in the blood, tissues or tumours they traverse. The availability of nutrients influences immune cell metabolism, but having a metabolite available does not mean a cell will necessarily use it. Cellular metabolism consists of an interconnected network that is influenced by at least 4 factors which we aim to better understand: 1. Metabolite / cellular nutrient availability How do immune cells sense changes in the context of their nutrient environment, and how are these signals transmitted? 2. Metabolite transport into the cell How are metabolite transporters regulated during immune cell activation and in the tumour microenvironment? 3. Metabolic enzyme and pathway activity Metabolic enzymes are often considered "household genes" for control experiments. But we are aiming to better understand how the activity of these enzymes is modulated. 4. Availability of enzyme cofactors Most, if not all, metabolic enzymes are dependent on substrate and cofactors. We are interested in the sensing of cofactor status and their effects on metabolic pathway activity and immune cell function. Not all immune cells use the same metabolic pathways even if metabolites are abundant, transporters and enzymes are expressed, and cofactors are available. The response can be regulated by growth factors, cytokines, or immune cell receptor signaling, and we aim to better understand the signals that provide the instructions for which metabolic pathway to use with in the setting of immune homeostasis and during an anti-tumor response.
Dr. Nada Lallous
My primary research goal is to employ a multidisciplinary approach — proteomics, genomics, biophysics, structural biochemistry, molecular and cellular biology— to identify novel therapeutics for patients with advanced forms of cancer. My research program is currently focused on studying the role of transcriptional condensates in prostate cancer (PCa) progression and treatment resistance. Designing better therapeutics for PCa patients relies on understanding the structure-function relationship of the androgen receptor (AR), the key driver of PCa progression and treatment resistance. Getting high-resolution structural information of the AR has proven challenging due to heterogeneity dictated by AR’s disordered N-terminal domain (NTD). Proteins containing intrinsically disordered regions (IDR) have been shown to form liquid-like condensates via a mechanism known as phase separation. We recently confirmed that full-length AR also forms such condensates upon stimulation with dihydrotestosterone (DHT) in prostate cancer models and in vitro. These condensates exhibit liquid-like properties and are hubs for transcription. These transcriptional hubs are essential for the execution of oncogenic programs and for controlling the partitioning of cancer therapeutics, thus dictating the clinical outcome of a specific treatment. Our specific goals are to: 1) Demonstrate that these condensates are hallmarks of cancer cells, 2) Understand what genetic/epigenetic factors drive their formation, 3) Identify proteins/nucleic acids involved in these condensates, and 4) Exploit them to identify novel cancer therapeutics.
Dr. Wan Lam
Dr. Lam’s laboratory at the BC Cancer Research Institute 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 involvement of developmental genes and non-coding RNA in cancer (2) the biology of lung cancer and COPD in smokers, former smokers, and non-smokers, (3) immune cells in the tumour microenvironment, (4) the genetic basis of aggressiveness, metastasis, and treatment response, and (5) molecular mechanisms of environmental carcinogenesis.
Admin Email: cclugston@bccancer.bc.ca
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.
Admin Email: cclugston@bccancer.bc.ca
Dr. Jonathan Loree
Jonathan Loree is a medical oncologist at BC Cancer with an interest in GI malignancies. He completed his medical oncology fellowship at BC Cancer and subsequently undertook a translational research fellowship at MD Anderson Cancer Center where he completed a Master’s of Science before returning to British Columbia. His research focus is translational research and biomarker development in colorectal cancer and neuroendocrine neoplasms and he serves as the co-chair of the colon cancer disease site for the Canadian Cancer Trials Group.
Dr. Kelly McNagny
Dr. Kelly McNagny obtained a BSc in Biology and Biotechnology at Worcester Polytechnic Institute (WPI) in Massachusetts and subsequently a PhD in Cellular Immunology at the U of Alabama at Birmingham (UAB). At UAB he worked with Dr. Max D Cooper, a founding father of B cell immunology, and his research focused on cell surface proteins that regulate B cell maturation and homing. He then moved to the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany where he performed postdoctoral studies with Dr. Thomas Graf and his work focused on transcriptional control of stem cell fate and the commitment to macrophage, eosinophil and thrombocyte development. He also identified a number of novel hematopoietic stem cell surface proteins (the CD34 family) and this then became the research focus of his own laboratory at The Biomedical Research Centre, at the University of British Columbia in Vancouver. He is currently a full professor in the departments of Biomedical Engineering and Medical Genetics where his work focuses on stem cell behaviour, innate immune responses, inflammatory disease, cancer biology and immunotherapeutics. His research relies heavily on the use of transgenic mice and animal models of human inflammatory disease as well as high-throughput “omics”technologies to reveal the immune components that determine the outcome of human disease. Nationally, he has filled leadership roles in the Stem Cell Network Centre of Excellence, the Centre for Drug Research and Development and the AllerGen Network Centre of Excellence. He is currently Co-leader of the Immunotherapeutics Cluster at UBC and is UBCs Delegate to CIHR. Twitter: @KMcNagnyLab.
Dr. Andrew Minchinton
Tumour Biology and Immunology, Molecular Biology and Metabolism, Cancer Therapy: Drug Development, Delivery, and Radiation Therapy
The tumour microenvironment is heterogeneous, both biochemically and structurally. Abnormal vasculature (with inter-vascular distances reaching 300µm or ~40 cell diameters) and dysregulated cell proliferation result in microregional gradients in nutrients, oxygen and drugs.
This biochemical and structural heterogeneity has consequences for cancer treatment. Cells located far from blood vessels are difficult for drugs to reach and because they have little oxygen, are resistant to radiotherapy.
Our group is interested in how the tumour microenvironment influences anticancer treatments including radiation and chemotherapy and have developed methodologies to quantitatively examine the extravascular distribution and effects of small and large molecular weight anticancer agents.
Dr. Gregg Morin
The general theme of our research program is to understand the functional mechanisms of somatically mutated or differentially expressed proteins in cancer pathology. The research integrates proteomic, genomic, chemical biology and bioinformatic technologies with more traditional biochemical and molecular biology methodologies. Our goal is to develop large scale integrative programs to understand the causes, and identify therapeutic targets, for multi-factorial diseases such as cancer. To learn more about Dr. Morin's research, read The Protein Link to Cancer, published in the BC Cancer Foundation Spring 2015 Partners in Discovery magazine.
The functions of most proteins are defined by or mediated through interactions with other proteins. These interactions are organized into complex networks regulated, in part, through modulation of protein phosphorylation by an elaborate interconnected system of kinases and phosphatases. We use quantitative proteomic techniques to study how protein networks, protein-protein interactions and post-translational modifications are aberrantly regulated in cancer.
Admin Email: alroth@bcgsc.ca
Dr. Lucia Nappi
Dr. Nappi is a clinician scientist medical oncologist. Her major research focus involves:
1. Study of molecular mechanisms mediating resistance to the targeted and chemotherapy agents in genitourinary tumors;
2. Drug discovery
3. Identification of new biomarkers for the diagnosis and treatment response/resistance in patients with genitourinary malignancies.
Dr. Brad Nelson
Dr. Nelson is a native of Vancouver BC. He received his B.Sc. from the University of British Columbia in 1987 and Ph.D. from the University of California at Berkeley in 1991. He completed postdoctoral training with Dr. Phil Greenberg and held faculty positions at the Fred Hutchinson Cancer Research Center and University of Washington in Seattle. In 2003, he became the founding Director of the BC Cancer Agency's Deeley Research Centre in Victoria BC. He is a Professor of Medical Genetics at the University of British Columbia and a Professor of Biochemistry/Microbiology at the University of Victoria. Dr. Nelson’s lab uses genomic and molecular approaches to study the immune response to cancer, with an emphasis on ovarian and lymphoid cancers. As Co-Director of the BCCA’s Immunotherapy Program, he is leading a phase I clinical trials program focused on adoptive T cell therapy for gynecological cancers, leukemia, lymphoma, and other malignancies. His team is developing innovative genetic engineering approaches to create more potent and precise T cell products for the treatment of cancer.
Dr. Torsten Nielsen
Prof Torsten Nielsen is an MD/PhD clinician-scientist in the Department of Pathology, who specializes in sarcomas and breast cancer. He works to translate genomic discoveries into practical clinical diagnostics and treatments. Some of his successes include the development of new diagnostic immunohistochemistry and nanoString assays for sarcomas and breast cancer molecular subtypes, international standardization of Ki67 testing, FDA and EU clearance of the PAM50 (Prosigna) assay for breast cancer risk, and contributions to clinical trials for fusion oncogene sarcomas and for the safe de-escalation of breast cancer chemo- and radiotherapy in low risk women. His current projects listed at www.gpecdata.med.ubc.ca/torsten/ActiveResearch.html and current lab members at www.gpecdata.med.ubc.ca/torsten/Lab.html
Admin Email: jamie.s.yu@ubc.ca
Dr. Daniel Renouf
Tumour Biology and Immunology, Molecular Biology and Metabolism, Cancer Therapy: Drug Development, Delivery, and Radiation Therapy
Daniel Renouf is a medical oncologist at the British Columbia Cancer Agency, Vancouver Centre, and an Assistant Professor at the University of British Columbia, Department of Medicine.
He received his Doctor of Medicine from the University of Alberta and completed his internal medicine and medical oncology training at the University of British Columbia and British Columbia Cancer Agency. He undertook further training in early drug development and gastrointestinal oncology at Princess Margaret Hospital and the University of Toronto, and obtained a Masters of Public Health from Harvard University.
Daniel’s research interests include developmental therapeutics, genomics, and biomarker development within gastrointestinal cancers, with a focus on pancreatic cancer. He is the leader of the BC Cancer Agency Phase I program, the Co-Director of Pancreas Centre BC and is the Co-chair of the Canadian Cancer Trials Group Pancreatic Cancer disease group.
Dr. Arefeh Rouhi
Drug resistance is one of the main treatment barriers in cancer therapy. Understanding how resistance emerges and how to overcome it are crucial to the development of new therapeutics. I am interested in understanding the molecular mechanisms of drug resistance as well as relapse in acute myeloid leukemia (AML) and multiple myeloma (MM). Factors such as tumor heterogeneity as well as cell intrinsic and microenvironmental changes lead to drug refraction. Understanding these mechanisms and creating novel drug combinations targeting multiple tumorigenic pathways, will result in a more specific, efficient and sustained therapy with potentially less side-effects.
Dr. Marianne Sadar
Genomics and Computational Biology, Tumour Biology and Immunology, Molecular Biology and Metabolism
The major focus of my research is to develop therapies that will delay or prevent tumour progression and emergence of hormone independence in prostate cancer. Current treatment for the onset of early stages of prostate cancer is the removal of male hormones, also called androgens, by either drug or surgical treatments. While initially effective in reducing cancer symptoms and PSA levels, this treatment is unable to completely and permanently eliminate all prostate cancer cells. After a predictable initial response to treatment, there is a relapse as the cancer progresses to a more aggressive androgen-independent stage. An early sign of progression to androgen independence, related to reduced survival, is the reappearance of elevated serum levels of PSA. The proteins that regulate the expression of the PSA gene have been shown to correlate well with the progression of prostate cancer, with both gene expression and the disease going from an androgen-dependent to an androgen-independent stage. One of these proteins is the one that actually recognizes and interacts directly with androgens and is called the androgen receptor. Thus the major objective of one area of my research program is to identify the molecular mechanisms that orchestrate the behaviour of proteins such as the androgen receptor during the progression of prostate cancer to androgen independence.
Dr. David Schaeffer
Dr. Schaeffer is an associate professor in the Department of Pathology & Laboratory Medicine at University of British Columbia and the Head of the Department of Pathology and Laboratory Medicine at Vancouver General Hospital (VGH) where he practices as a gastrointestinal pathologist. Dr. Schaeffer obtained his medical degree from the Johannes Gutenberg University of Mainz, Germany. After a residency program in Anatomical Pathology in Vancouver he completed his gastrointestinal pathology fellowship at Mount Sinai Hospital in Toronto. Dr. Schaeffer is a co-director of Pancreas Centre BC and also heads the Gastrointestinal Biobank (GIBB) at VGH. He has an active research program focusing predominately on translational research in colonic and pancreatic cancer.
Admin Email: lisa.scully@vch.ca
Dr. Kirk Schultz
My work has evaluated clinically driven issues related to hematopoietic cell transplantation. Clinical investigations have focused on age-related factors affecting graph-versus-host disease (GVHD), graft-failure and graft-versus-leukemia (GVL). Laboratory investigations have used pre-clinical models and the performance of correlative studies in humans to investigate the mechanisms of GVHD and GVL and to develop experimental approaches to modulate these phenomena.
Our laboratory has evaluated the hypothesis that manipulation of MHC class II antigen presentation can alter T cell responses to endogenous antigens. We have investigated the importance of two MHC class II antigen presenting cells in vivo, B cells and dendritic cells, for T cell priming responses to leukemia, and minor histocompatibility antigens (MiHC). We have also investigated whether inhibition of MHC class II antigen presentation by lysosomotropic agents such as chloroquine can inhibit T cell responses to MiHC and development of GVHD. We have translated these pre-clinical observations into clinical studies. We have been one of the first groups to identify chronic GVHD biomarkers in children.
Dr. David Scott
The focus of the research in the Scott laboratory is aimed at improving outcomes of patients with lymphoid cancers through precision medicine. This involves unravelling the molecular determinants of treatment failure, applying cutting edge technology to patient biopsies, and then translating that knowledge into assays that can be used to guide treatment management. These approaches have led to the development of prognostic and predictive biomarkers for classical Hodgkin lymphoma, diffuse large B-cell lymphoma and mantle cell lymphoma that are applicable to routinely produced formalin-fixed paraffin-embedded biopsies – allowing these assays to be used in clinical practice.
The poor outcomes seen when patients experience treatment failure have led to an emphasis on the biology of these cancers at the time point of relapse, exploring high-risk genetic features and evolution of tumors as they are exposed to immuno-chemotherapy. The Scott laboratory is now leading and co-ordinating correlative studies in clinical trials of treatment of relapsed and refractory aggressive B-cell lymphoma. Finally, the Scott laboratory has broadened the biobank at BC Cancer to enable the expansion of this research into chronic lymphocytic leukemia (CLL).
Admin Email: aleli.capuno@bccancer.bc.ca
Dr. Poul Sorensen
Dr. Poul Sorensen is a molecular pathologist specializing in the genetics and biology of pediatric cancers. Dr. Sorensen holds the Johal Endowed Chair in Childhood Cancer Research at the University of British Columbia (UBC), and is a UBC Professor of Pathology and a Distinguished Scientist at the BC Cancer Agency. Dr. Sorensen’s laboratory, located at the BC Cancer Research Centre, focuses on using both genetic and biochemical approaches to identify deregulated signaling cascades in childhood cancer cells. His group has discovered many novel genetic alterations in childhood cancer, including the EWS-ERG gene fusion in Ewing sarcoma and the ETV6-NTRK3 chimeric tyrosine kinase in congenital fibrosarcoma and secretory breast carcinoma. Dr. Sorensen’s work focusses on pathways involved in the tumor stress response. Tumor cells are continually exposed to diverse stress forms including nutrient deprivation, hypoxia, endoplasmic reticulum, oxidative, or genotoxic stress, or toxic drug or radiation exposure during patient therapy. Each stress form is potentially lethal unless tumor cells can acutely adapt to it. Dr. Sorensen’s group is focused on how stress adaptation occurs through acute changes in mRNA translation, including the molecular switches that allow tumor cells to reprogram their mRNA translatomes under stress, and how these mechanisms can be therapeutically targeted. Dr. Sorensen’s recent work also focusses on the identification and validation of novel immunotherapeutic targets specifically expressed on the surface of pediatric cancer cells. Indeed, Dr. Sorensen is also a principal investigator on the St. Baldrick’s Foundation Pediatric Cancer Dream Team grant, now known as the EPICC Team (Empowering Pediatric Immunotherapies for Childhood Cancer), and on the U54 program grant for the NCI-NIH Cancer Moonshot Pediatric Immunotherapy – Discovery and Development Network (PI-DDN) initiative. Recent work in Dr. Sorensen’s laboratory focus on identifying novel immunotherapeutic targets and develop targeted therapeutic approaches for high-risk childhood cancers.
Admin Email: carlai@bccrc.ca and mrouleau@bccrc.ca
Dr. Christian Steidl
Dr Steidl is an Associate Professor in the Department of Pathology (University of British Columbia) and Lymphoid Cancer Research (BC Cancer Agency). He is holding an MD degree from the University of Muenster, Germany, and a PhD equivalent degree from University of Witten-Herdecke, Germany. Dr Steidl has expertise in clinical malignant hematology, cytogenetics, molecular genetics, next-generation sequencing and functional genomics. Dr. Steidl joined the Centre for Lymphoid Cancer at the British Columbia Cancer Agency in 2006. He is currently supervising a translational research laboratory focusing on the pathogenesis of B cell lymphomas. Dr Steidl is most known for his work on biomarkers in Hodgkin lymphoma and discovery of novel gene fusions in B cell lymphomas. He has authored 74 refereed articles in the field of hematological malignanices and has been an invited speaker at many conferences. He also serves as a member of the Lymphoma Research Foundation’s Panel of Scientific Advisors and the Medical Expert Committee of the Cancer Research Society. Dr Steidl holds research funding as the principle investigator by the Canadian Institutes of Health Research (CIHR), the Leukemia and Lymphoma Society of Canada (LLSC), the Canadian Hematology Society (CHS), and is co-investigator on a Genome Canada grant to advance personalized treatments of lymphoid cancer patients. Dr. Steidl also holds a career investigator award by the Michael-Smith Foundation for Health Research and a New Investigator Award by the CIHR.
Dr. Peter Stirling
The Stirling lab is a vibrant research group embedded within the Terry Fox Laboratory at the BC Cancer Agency in Vancouver, Canada. The lab is using functional genomics, molecular biology, biochemistry, and advanced imaging in both the yeast model and cultured human cells to study fundamental mechanisms of genome maintenance and stability. Failure to maintain genome integrity leads to mutations that can promote tumour formation. Normal genome maintenance mechanisms can be overwhelmed by carcinogen exposure, or the presence of germline or somatic variants that induce genomic instability. Our work is aimed at determining the causes of genomic instability as an enabling characteristic of tumour formation, and exploring the potential of these early events to suggest novel therapeutic targets.
Dr. Fumio Takei
Natural killer (NK) cells have two major functions, namely killing of tumor cells and production of cytokines, in particular interferon-g. These functions of NK cells are triggered by cell surface receptors that recognize ligands on tumor cells or cytokines. NK cells also express inhibitory receptors that recognize MHC class I on normal cells. A balance between stimulatory and inhibitory receptors mediates anti-tumor NK cell functions and tolerance to normal cells. In our laboratory, we are studying how NK cells acquire those stimulatory and inhibitory receptors as well as their functions during their development and how the process of tumor cell killing is regulated. These studies will likely lead to new ways to enhance anti-tumor functions of NK cells without affecting self-tolerance.
Dr. Michael Underhill
Dr. Underhill’s research interests involve understanding how changes at the molecular level influence cell fate decisions and the subsequent series of events that are involved in establishment of a skeleton. The initial focus of his research was on understanding the importance of retinoic acid receptor-mediated signaling in bone formation (chondrogenesis). This scope has now broadened to include analysis of numerous factors in skeletal development. These studies involve extensive use of microarray-based strategies coupled with functioning profiling to delineate the genetic programs underlying chondrogenesis. Similar strategies are also being employed to identify the transcriptional networks operating within the osteogenic program. Knowledge gained from these studies will determine the molecular basis of human congenital skeletal defects and potentially lead to novel therapeutic avenues to promote bone and cartilage formation for the treatment of skeletal diseases such as arthritis and osteoporosis.
Dr. Leandro Venturutti
Dr Leandro Venturutti began his scientific career at the Faculty of Pharmacy and Biochemistry (University of Buenos Aires, Argentina), where he studied the structure and function of a protein lost in the hereditary neurodegenerative disease Friedreich Ataxia. Pursuing his profound interest in biomedical sciences and mechanisms of disease, he moved on to the cancer research field for his PhD studies. He devoted a significant part of his thesis work to exploring pathways of metastatic dissemination, identifying clinically useful predictive biomarkers, and developing novel therapeutic tools for breast and gastric tumors. Dr Venturutti completed his training working as a postdoctoral researcher at the Division of Hematology and Oncology (Weill Cornell Medicine, USA), where he investigated how recurrent mutations in aggressive B-cell lymphomas alter the epigenome and contribute to the early stages of malignant transformation. Dr Venturutti was recruited to the BC Cancer Research Institute in 2021 to start his own research group. His goals are to identify and understand the mechanisms driving the progression and dissemination of B-cell lymphomas, as a means to develop minimally invasive diagnostic tools, and novel prophylactic and curative treatments. His group exploits modern high-parameter technologies to study clinical specimens, and develops sophisticated models of disease to tackle profound biological questions with translational potential.
Dr. Ly Vu
The overarching goal of our laboratory is to understand the control of stem cells in development and diseases. Our research group is focused on uncovering novel mechanisms of post-transcriptional and translational regulation during normal and malignant hematopoiesis. We aim to develop innovative therapeutic approaches targeting these regulatory pathways in cancer.
While disruption of genetic and epigenetic mechanisms and altered signaling networks are commonly studied, the role post-transcriptional and translational regulation in tumorigenesis has only recently recognized. We are particularly interested in defining the regulation of mRNA decay and translation mediated by poly(A) tail length and RNA deadenylation complexes in the context of normal and leukemia stem cells. Despite the central role of mRNA decay and poly(A) tails in regulating and coupling RNA metabolism and translation, it is virtually unknown how these processes contribute to drive and maintain the self-renewal and oncogenic gene expression programs in stem cells and cancer. Our work will provide insights into this largely unexplored area and enable development of new therapies. The laboratory employs human and mouse models; a broad range of molecular biology methods and a global approach using next generation sequencing techniques to decipher regulation of gene expression at multiple layers from transcription to mRNA biogenesis and translation.
Admin Email: Akotzer@bccrc.ca
Dr. Yuzhuo Wang
Dr. Dong’s laboratory investigates the molecular mechanism by which prostate tumors develop therapy resistance with emphasis on RNA binding proteins that promote treatment-resistant disease progression. His lab applies computer-aided drug design to develop new anti-cancer drugs and RNA sequencing technology to explore cell-free circular RNA as diagnostic markers. Dr. Yuzhuo Wang, Ph.D., F.C.A.H.S. has a dual appointment as a Distinguished Scientist at the BC Cancer and Senior Scientist at the Vancouver Prostate Centre. He is a Full Professor in the Department of Urologic Sciences at UBC and the founder of the unique Living Tumor Laboratory (www/livingtumolab.com). Dr. Wang has authored >210 peer-reviewed articles (with an H-index of 78), 14 book chapters and edited two books (i.e. PDX models of human cancer and Tumor dormancy). Dr. Wang created a novel method for establishing patient-derived xenograft (PDX) cancer models that closely resemble patients’ malignancies from which they are derived. His group was the first to1) demonstrate the first generation PDXs can be used to study cancer and human immune cell interactions and for personalized cancer therapy; 2) establish the first in field and the only PDX model with the NEPC trans-differentiation; and 3) establish a panel of ADT-induced PDX dormancy models from hormone-naïve PCa PDXs. So far, his group has established over 300 high fidelity next generation PDX models of a variety of malignancies in his Living Tumor Laboratory. His next generation PDX cancer models have been effectively applied in a number of research areas, including (i) preclinical drug efficacy studies, (ii) discovery and validation of potential biomarkers and therapeutic targets, and (iii) evidence-based personalized cancer therapy Dr. Wang’s scholar contributions can be highlighted by a number of novel hypotheses he has proposed, such as hypotheses on “epithelial-immune cell transition (EIT)”, “cancer-generated lactic acid is critical, immunosuppressive metabolite rather than a ‘waste product’ (which has been believed for more than 90 years)” and “Tumor dormancy is a non-genetic disease”. Based on his innovative theories and ideas, he has maintained a high level of grant funding that have led to widely recognized, ground-breaking research, including the discovery of several new therapeutic targets and the development of novel therapeutics targeting, among others, GATA2, BIRC6, MCT4, HP1-alpha and B7H4 genes. Based on his discoveries, two biotech companies (e.g. LAST Innovation Ltd.) have been formed in Canada. He has been mentoring over 90 graduate students, postdoctoral fellows and co-op students. To date, many of them are employed as clinical doctors, academic professors, and scientists in industry. Dr. Wang has been invited to give > 200 lectures worldwide including at the most prestigious prostate cancer meetings. He has received many awards for his academic achievements in cancer research. Notably, he has been inducted as a Fellow of the Canadian Academy of Health Sciences (FCAHS) since Sept, 2018.
Dr. Amina Zoubeidi
Dr Zoubeidi research program is aimed at uncovering mechanisms of CRPC with a special focus on the resistance to modern anti-androgen therapy. In particular, a subset of patients who relapse following ARPI therapy exhibit lineage switching whereby tumours shed their dependence on AR signaling and emerge with neuroendocrine features. These tumours, termed treatment induced neuroendocrine prostate cancer (t-NEPC), carry an extremely poor prognosis and, to date, treatment remains decades old cytotoxic chemotherapy which carries a short-lived response at the cost of significant toxicity. Thus, the need to develop targeted treatments for this devastating disease is of paramount importance. She published have 70 peer-reviewed manuscripts in Cancer Discovery, Nature communication, Cell Report, Cancer Research and others. She is a Michael Smith Scholar and was awarded the prestigious PCF Young Investigator Award in 2010 and since then have received substantial funding awards from national and international funding agencies as a principal investigator or co-investigator that together total over $14 million. Her track record of research excellence is underscored by numerous accolades from the American Association for Cancer Research, the American Urological Association, the Northwest Urological Society and others. She had the honor of being invited to speak at numerous national and international conferences on molecular mechanisms and drug targets of PCa, including AACR and CCRC and as a visiting professor at different Universities. She serves on several grant panel review committees including NIH, CIHR, PCa Canada, Prostate Cancer Foundation USA and others. She is a member of the editorial board of Endocrine Related Cancer and ad hoc reviewer for numerous journals including EMBO, Oncogene, the AACR journals to name a few. In recognition of her meritorious achievements, she was awarded the UBC Faculty of Medicine Distinguished Achievement Award for overall early career excellence, her trainees hold award from DOD, CIHR, PCF, PCC and others agencies.