Interdisciplinary
Oncology Program
Molecular Biology and Metabolism
Dr. Marcel Bally
Dr. Bally received his BSc (1977) and MSc (1979) degrees in biology from Texas A&M University. He obtained his PhD from the Department of Biochemistry at the University of British Columbia (1984). Dr. Bally is an authority in drug delivery, anti-cancer drug combinations and drug evaluation in animal models of disease. His research interests focus on the development and characterization of novel lipid-based nanoparticle formulations for use in the treatment of cancer. Dr. Bally’s is one of the founders of the Center for Drug Research and Development; an organization aimed at addressing the growing commercialization gap between discoveries made in academia and the opportunity to develop this technology to a stage where investments can be made to support clinical and commercial development. His research can be linked directly to regulatory approved drugs, one product in late stage development and several others in early stage clinical trials and preclinical development. This would include (i) Myocet; (ii) Marqibo® and (iii) Vyxeos.
Dr. Angie Brooks-Wilson
Dr. Brooks-Wilson leads a cancer genetics research laboratory at the Genome Sciences Centre of the British Columbia Cancer Agency here in Vancouver, BC. Her current work focuses on the genetics of healthy aging and the genetics of susceptibility to cancer, particularly lymphoid cancers, in families and populations. She leads the Healthy Aging Study in which exceptionally healthy elderly individuals (‘Super-Seniors’) are helping to determine the genetic influences that contribute to healthy aging and protect against age-related diseases.
Admin Email: vzhu@bcgsc.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
Dr. Mads Daugaard is a molecular biologist specialized in tumour-associated stress signaling pathways and tumour targeting systems. Dr. Daugaard’s ongoing research focuses on molecular and biochemical events underlying T cell exclusion in tumors; chromatin context-dependent DNA repair; and development of resistance to chemotherapy. Another aspect of Dr. Daugaard’s research relates to discovery and development of novel tumour targeting systems based on parasite-derived recombinant proteins relevant for therapeutic and diagnostic applications in cancer. Therapeutic development programs include CAR-T and bi-specific immunotherapies, targeted drug-delivery, and oncolytic virus systems. Diagnostic programs include molecular pathology, circulating tumor cells, and biomarker discovery in bodyfluids.
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. Martin Gleave
Dr. Gleave is a clinician-scientist and urologic surgeon whose clinical practice focuses on urologic oncology in a multi-disciplinary environment at the leading edge of assessing new technologies and treatments across both localized and advanced cancers. His research characterizes molecular mechanisms mediating treatment resistance in cancer, focusing on adaptive survival responses that drive acquired treatment resistance, and designing combination co-targeting strategies to create conditional lethality and improve cancer control. He patented several anti-cancer drugs and in 2001 founded OncoGenex Pharmaceuticals to develop OGX-011 and OGX-427, inhibitors of cytoprotective chaperones clusterin and Hsp27 now in Phase III and Phase II trials world-wide. He has co-founded several other companies including Sitka Pharma, TRiADD, and Sustained Therapeutics.
Dr. Sharon Gorski
Dr. Gorski completed a PhD in Biology and Biomedical Sciences at Washington University School of Medicine, St. Louis, MO in 1999. She then conducted postdoctoral studies at the BC Cancer where she utilized genomics approaches to study cell death and cell survival pathways. Dr. Gorski is currently a Distinguished Scientist at Canada’s Michael Smith Genome Sciences Centre at BC Cancer and a Professor in the Department of Molecular Biology and Biochemistry at Simon Fraser University. Her research program includes analyses of cell stress responses and cancer-related signaling pathways, with a focus on breast and pancreatic cancers.
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. 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. David Kitts
My research discipline is Food Chemistry and Toxicology. I employ many aspects of food chemistry principles to understand the cellular and molecular mechanisms of both nutrient and food toxicant action in living organisms. Recently, my laboratory has focused on characterizing the mechanisms of antioxidant and prooxidant activity for many naturally occurring animal and plant constituents, in addition to derived products from food processing. Moreover, we have focused also on the interaction between food constituents and transition metals in modulating generation of free radical and peroxidation reactions that can alter stability of lipids in both food materials as well as biological membranes.
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. Nathan Lack
Dr. Nathan Lack is a Senior Research Scientist at the Vancouver Prostate Centre.
He obtained a DPhil (PhD) in Pharmacology from the University of Oxford in 2009 and then did a Postdoctoral Fellowship at the Vancouver Prostate Centre with Dr. Emma Guns and Professor Paul Rennie. Nathan became an Assistant Professor at Koç University in the School of Medicine (Istanbul) in 2011 and was awarded Associate Professorship in 2015. In addition to his academic research, Nathan previously worked for AnorMED Inc., where he was involved in the development of the FDA-approved therapeutic Plerixafor.
His laboratory works to better understand the molecular underpinnings of prostate cancer to develop more effectively treatments for this common disease. Extensive clinical and basic research has shown that Androgen Receptor (AR)-mediated transcription drives the proliferation and growth of almost all prostate cancers. His group currently studies a diverse group of problems related to AR signaling including:
-
Identification of small molecule AR inhibitors that target novel sites
-
Characterization of non-coding mutations that affect androgen receptor signaling
-
Development of novel functional genomic techniques to study AR-mediated transcription
Since it’s initiation, the Lack laboratory has obtained extensive funding from national, international and industrial sources.
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. 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
Genomics and Computational Biology, Tumour Biology and Immunology, Molecular Biology and Metabolism
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. Christopher Ong
Dr. Christopher Ong is a Senior Research Scientist at the Vancouver Prostate Centre and is an Associate Professor in the Department of Surgery at the University of British Columbia. He is a Michael Smith Foundation for Health Research Senior Scholar. Dr. Ong’s research interest is focused on studying disease mechanisms at the molecular and cellular levels. A strong underlying emphasis of his research efforts is in translational research with the aim of translating laboratory-based discoveries into tangible clinical applications.
In particular, his research interests are primarily focused on understanding molecular mechanisms that control treatment resistance of prostate cancer. Dr. Ong believes that insights into these pathways will guide the development of new molecular targeted therapeutics for treating castration resistant prostate cancer.
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. Miriam Rosin
Research Interests:
-
Development of biomarkers to identify early biological changes in the premalignant process
-
Human studies using genetic and phenotypic biomarkers of exposure and risk
-
Reduction in cancer risk through chemoprevention
-
The potential role of reactive oxygen species in chromosomal breakage in humans: identification of mutations that increase sensitivity to such agents
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. 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
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. 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. 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. Andrew Weng
My research program focuses on the pathogenesis of lymphoid malignancy and entails two major arms. First, we have explored the role of NOTCH1 and other oncogenes/tumor suppressors in the genesis and propagation of T-cell acute lymphoblastic leukemia (T-ALL) including studies on downstream target genes/pathways and identifying mechanisms operative in leukemia stem cells. We have addressed these questions in cells from different developmental stages and tissue contexts on the hypothesis that preset epigenetic programs may restrict the oncogenic trajectories available to the cells as they undergo the initial stages of transformation and clonal establishment. Many of our findings have direct clinical relevance in that they serve as basis for the development of rational therapies that target disease-specific phenotypes.
As a second and more recent focus, my lab has explored the use of state-of-the-art mass cytometry (CyTOF) to obtain highly resolved phenotypic maps of heterogeneous cell populations in present in patient lymphoma biopsy samples including both malignant and reactive immune cell compartments. We have used this methodology to characterize intratumoral heterogeneity/subclonal diversity among malignant cell populations and stereotyped or patient-specific immune responses. This work is also of direct clinical relevance in providing detailed phenotypic characterizations that are required in order to define biomarkers for lymphoma classification and prognosis, and monitoring of patient-specific responses to therapy.
Dr. Stephen Yip
Genomics and Computational Biology, Molecular Biology and Metabolism
Stephen completed his combined M.D-Ph.D. training followed by 4 years of neurosurgical training at UBC. He switched to neuropathology and obtained his Royal College certification in 2007. He completed fellowship training in molecular neuro-oncology at the Massachusetts General Hospital under the mentorship of Dr David Louis (RC Clinician Investigator Program) and molecular genetic pathology at MGH/Harvard Medical School under the supervision of Dr John Iafrate. He currently practices neuropathology at Vancouver General Hospital and is the director of the Cancer Genetics & Genomics Laboratory at BC Cancer. His research interests include dissecting the molecular pathology of brain and spine cancers, practical deployment of advanced diagnostic assays, and the application of deep learning as an integrative diagnostic tool.
Dr. Amina Zoubeidi
Molecular Biology and Metabolism, Cancer Therapy: Drug Development, Delivery, and Radiation Therapy
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.