The people of UBC Pathology and Laboratory Medicine are the key to our success.
Below is a list of faculty who are currently supervising graduate students, or are actively seeking graduate students. When contacting potential supervisors through email you must include your letter of intent, current CV, publication list (if applicable), copies of post-secondary transcripts, and your TOEFL/GRE scores – preferably merged into one PDF document.
*Indicates this supervisor is currently seeking new students and is willing to be contacted by potential students in the manner mentioned above.
Dr. Aparicio’s work encompasses the fields of cancer genomics, mouse genetic models, high throughput screens, and translational breast cancer research.
Poul Sorensen is currently the Johal Chair in Childhood Cancer Research, based at UBC/BC Cancer Agency, Vancouver, Canada. His research focuses on the aberrant signalling pathways that are involved in the development of certain pediatric and breast cancers.
Dr. Huntsman was part of the team that discovered EMSY, a new gene related to ovarian cancer. His current focus of study is the genetic predisposition to ovarian cancer, and the role of E-cadherin gene mutations in patients with hereditary diffuse gastric cancer.
Dr. Karsan’s reasearch focuses on myelodysplastic syndromes, innate immune signaling in vascular and hematopoietic function and the role of Notch in cardiovascular development and angiogenesis.
As co-director of the Genetic Pathology Evaluation Centre at Vancouver Hospital Dr. Nielsen leads several active tissue microarray and gene expression profiling projects, focussing on the confirmation and clinical correlation of results from breast cancer and sarcoma basic science investigations, and their translation into diagnostic and predictive tests. As an independent principal investigator, Dr. Nielsen direct his lab in a research program to develop much-needed systemic treatments for sarcomas, particularly synovial sarcoma and tenosynovial giant cell tumor, neoplasms most commonly occurring in the limbs of young adults, and for the intrinsic subtyping of breast cancer.
Dr. Gilks leads a dynamic research program focused on gynecological cancers. In addition, he is also a Co-Founder and Co-Director of the Genetic Pathology Evaluation Centre (GPEC), a collaborative research venture of the Pathology Department, and the Prostate Research Centre at Vancouver Hospital and the BC Cancer Agency, which utilizes tissue microarray technology to uncover novel cancer biomarkers.
Dr. Lam’s primary research interest is in understanding the events leading to cancer progression. Early detection and treatment is key to a favorable prognosis in cancer. His laboratory has developed novel whole genome approaches for tracking genetic, epigenetic and gene expression changes in order to identify genes and pathways critical to cancer progression, and signatures for treatment response.
The major focus of Dr. Sadar’s research is to develop therapies that will delay or prevent tumour progression and emergence of hormone independence in prostate cancer.
The research conducted in Dr. Bally’s laboratory focuses on developing improved protocols for the treatment of cancer. Clinicians have an arsenal of very potent drugs available for treatment of cancer. These drugs, however, lack specificity and often produce severe, life threatening, toxicities. Further, optimal therapeutic effects of any anticancer drug appear to be dependent on their use in a combination setting. Multi-agent therapy is the standard by which cancer is treated. Based on this understanding, research in the laboratory is designing methods and strategies for capturing the benefits of drug combination effects that are often first measured using cell based screening assays. Although basic research interests include evaluation of novel targeted anticancer drugs, Dr. Bally’s group is also comprehensively pursuing combinations of existing, already approved, cytotoxic agents. The latter studies will provide the proof of concept data needed to demonstrate the value of pursuing anticancer drug combination products. These products will be of particular interest when used with emerging targeted agents, but will also demonstrate the potential to develop new products that may consist of two or more targeted agents.
Dr. Suzanne Vercauteren
Dr. Vercauteren is interested in the genetic events that lead to leukemia. At the moment, I am working on several projects including looking at mutations in microRNAs in a large number of AML patients. WE are also determining whether microRNA expression can be measured by flowcytometry. In addition, I am sequencing the RNA profile on two patients with a very rare type of leukemia, plasmacytoid dendritic cell leukemia to see if we can find a common genetic event that may cause this disease.
Dr. Lim’s research interests centers around the biology of cell adhesion molecule signaling. The integrin family of adhesion receptors mediates cell adhesion/migration and play important immunological roles in normal physiological function and in disease states. The lab combines state of the art microscopy techniques for imaging of live cellular events as well as classical protein biochemistry to investigate signal transduction at the molecular level. A central line of investigation involve the alpha4 integrins, cAMP dependent protein kinase (PKA) and their functional outcomes in chemotherapeutic resistance in leukemias.
Dr. Calum MacAulay
Dr. MacAulay’s lab focuses on early cancer detection and treatment in Lung, Oral, Colon, Cervix using advanced optical imaging techniques with and without molecular contrast agents. Computer assisted and fully automated quantitative cytology and histology systems for screening, diagnosis and prognosis.
Most solid tumours contain cells that are poorly oxygenated, and these hypoxic tumour cells are refractory to a variety of cancer treatments including radiation therapy and chemotherapy. Not only are hypoxic cells the most difficult tumour cells to kill with conventional therapies, but hypoxia also promotes a more aggressive tumour phenotype. In the clinic, patients with primary tumours that contain large fractions of hypoxic cells have poor outcome, due in large part to limited treatment response and the presence of distant metastatic disease. Dr. Bennewith’s lab is interested in the role of tumour hypoxia (and the tumour microenvironment) in cancer therapy and in the development of tumour metastases.
Reversible protein tyrosine phosphorylation is a prominent mechanism utilized in controlling these signalling pathways: protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) co-ordinately determine the tyrosine phosphorylation status and the function of a particular substrate protein. Perturbations of such signalling pathways underlie a variety of pathological conditions. Aberrant tyrosine phosphorylation due to malfunctioning PTKs is well established as the basis of several human diseases, in particular human cancers. It is becoming apparent that defective or deregulated PTPs are likewise critical in the development and progression of some human diseases such as cancer and diabetes. Consequently, PTPs are excellent targets for disease intervention.
Dr. Schultz’s lab is attempting to harness the immune system to cure child leukemia and to use blood-derived stem cells to cure other life threatening childhood diseases. Currently, blood and marrow transplantation (BMT) is the only successful form of immune therapy for childhood leukemia. Dr. Schultz’s research group focuses on harnessing the immune forces unleashed by BMT to improve immune therapy for childhood leukemia. By increasing their understanding of these important immune forces, they hope to also improve the ability to provide safe tissue transplants when needed. Lastly, the group is focused on developing approaches to extend the ability to use blood-derived stem cells to regenerate damaged tissues, correct the immune system, and save children and adolescents from life threatening childhood diseases.
Dr. Rennie is a PhD research scientist. His current research is aimed at determining how androgens regulate gene transcription and how to use this knowledge to prevent progression to androgen independence in prostate cancers. He is also developing targeted oncolytic viruses and creating a new class of anti-androgen receptor drugs to treat drug and hormone-resistant prostate cancers.
The Lockwood lab utilizes and integrative genomic approach to identify and charaterize gene and pathways involved lung cancer initiation, progression and response to therapy.
Currently there are still no cures for one in every six children suffering from cancer.
Dr. Philipp Lange, Canada Research Chair in ‘Translational Proteomics of Pediatric Malignancies’, develops new diagnostic and therapeutic approaches to detect and treat children suffering from cancer earlier, better and with reduced impact on their life.
His research focuses on the aberrant cellular signaling pathways that are involved in select pediatric cancers. He applies and develops proteomics technologies to detect all proteins in a cell and he monitors how they are changed by post-translational modification (PTM). Such PTM can fundamentally alter the function of a protein. He then explores the role of these PTMs in cancer using cell biology as well as biochemistry and attempts to find new ways of using this knowledge to improve diagnosis and treatment of cancer in children.
Dr. Philipp Lange complements his experimental work with bioinformatics. He focuses on the development of algorithms for the prediction of protein function and the development of new biological knowledgebases to improve the functional analysis of genomics and proteomics data and guide personalized treatment decisions.
Dr. Kizhakkedathu’s research focuses on Macromolecular Therapeutics:
A) High molecular weight Iron chelators for Chelation therapy
B) Polymeric Antidotes to reverse the clotting effects of anticoagulants
Polymer Cell Derivatization Technology (Universal blood donor cells and Cell based therapeutic carriers
Development of Blood Compatible Surface Coatings
Development of Polymeric Reagents for Proteomic Applications
Dr. Scott’s laboratory is primarily focused on three primary areas of research: 1) investigation of the potential therapeutic use of “immunocamouflaged” cells/tissues in transfusion and transplantation medicine; 2) prevention of viral invasion via viral inactivasion and target cell modification via immunocamouflage; and 3) examining whether the intraerythrocytic chelation and redox-inactivation of the hemoglobin-derived heme and iron present in the sickle and thalassemic RBC can slow/prevent premature red cell destruction.
The general area of interest in Dr. Pryzdial’s laboratory is the novel function of blood proteins. Combining biochemistry and recombinant protein techniques our studies focus on the regulation of clot formation and virus infection. Particular emphasis is placed on advancing our understanding of heart disease and transfusion science.
The research in Dr. Devine’s laboratory is focused primarily on aspects of transfusion medicine. Specifically, we are interested in improving the quality of blood products, particularly platelets, that are given to patients. To do this, we must understand the processes that cause a loss of platelet quality under standard blood product storage conditions. Using techniques ranging from classical measures of platelet physiology to the application of proteomics techniques to study blood product storage, we identify processes that can be modulated to preserve the cellular function for better transfusion outcomes. We also do research on new technologies that improve the safety of blood products including pathogen inactivation processes.
The long-term objective of Dr. Luo’s research is to elucidate the molecular mechanisms of viral myocarditis, with particular emphasis of the roles of the host protein degradation systems, including the ubiquitin-proteasome system and the autophagy, as well as the host signaling pathways, in the pathogenesis and progression of viral myocarditis.
Dr. Yang’s research interests focus on two major areas. The first one is the molecular biology and pathogenesis of coxsackievirus, a positive single-stranded RNA virus. In this area of study, Dr. Yang’s laboratory is working on the mapping of the viral gene structures responsible for viral translation initiation and cardiovirulence by mutational analysis. They also identify host proteins specifically interacting with viral RNA and/or viral proteins. Based on these studies, antiviral drugs including antisense oligonucleotide, ribozyme and si/mi-RNA targeting these key genes are being developed for the treatment of coxsackievirus-induced myocarditis. To enhance the drug effectiveness, nanobiomedical approaches are employed to deliver these gene drugs specifically to certain cell populations. These drugs are being evaluated in vitro and in mouse models. The second area of Dr. Yang’s interest is the study of host gene responses to viral infection. The focus of this study is the transcriptional analysis and functional characterization of mouse genes encoding determinants of cardiac susceptibility to coxsackievirus infection. Differential mRNA display and microarray analyses have identified known and unknown candidate genes as well as microRNAs potentially involved in heart disease development. Tet-On/Off inducible cell lines and genetically modified mouse models are employed to study the roles of selected genes and microRNAs in signal transduction pathways leading to myocyte apoptosis or cardiac hypertrophy. These studies have great potential to discover new targets for gene therapy and molecular markers for diagnosis of viral myocarditis and other related infectious diseases.
Dr. McManus’ basic and clinical investigative program is focused on mechanisms, consequences, detection and prevention of injury and repair involved in inflammatory diseases of the heart and blood vessels, with particular emphasis on enteroviral infections of the heart and transplant vascular disease. He works in an interdisciplinary setting on questions for which answers are critically enabled by computational sciences including biomarker discovery and validation, information acquisition, annotation, and use, and registry development to support heart and lung research.
While Dr. Granville’s research at iCAPTURE is primarily focused on understanding the mechanisms of vascular injury and dysfunction and discovering novel therapeutic targets and strategies to combat atherosclerosis, heart transplant rejection and myocardial infarction, recent serendipitous discoveries have resulted in a greater focus on normal and accelerated aging, degeneration and cardiovascular disease.
Dr. Hill’s field of study has been concerned with lipid and lipoprotein research and its relationship with coronary artery disease. More specifically, his research has focused on the structure-function relationships of lipolytic enzymes that influence the levels of circulating cholesterol and triglyceride.
Dr. Seow specializes in smooth and skeletal muscle cell biology/physiology. His current research focus is on the mechanical function, ultrastructure and biochemistry of airway smooth muscle, in health and disease. His other interests include skeletal muscle mechanics, ATPase cycle associated with the crossbridge cycle, energetics of muscle contraction, and mathematical modeling of muscle function.
Dr. Jacqueline Quandt joined the department in April 2009 as an Assistant Professor. Jacquie completed her undergraduate degree (Microbiology & Immunology) and doctoral degree in neuroimmunology (Pathology) at UBC where she focused on lymphocyte trafficking at the level of the blood-brain barrier. In 1999 she set off for a post doctoral fellowship at the National Institutes of Health in Bethesda, MD to work on animal models of multiple sclerosis. Over the last four years leading an Animal Models Unit her research focused on immunological and genetic parameters in autoimmunity as well as the development of novel therapeutic applications. Jacquie’s research at UBC continues to focus on immunological damage and repair related to multiple sclerosis and other diseases of the nervous system.
As you read this paragraph, two infants in the world will have died from an infection for which there is an effective vaccine. Worldwide we could save 5 million infants every year—if only we could immunize them on time. There appear to be many reasons—none of them insurmountable—why the world fails to save the lives of these children. The work in our lab focuses on part of the science to help solve this problem: we are developing a vaccine system that with only one immunization given at birth will protect from a wide range of specific infectious diseases, as well as from allergies, autoimmune diseases and malignancies, for the entire life. We are systematically analyzing the human neonatal and infant response to danger signals (e.g. TLR-ligands) and vaccines. This way, we will learn what aspects of the newborn’s immune system work well. With that knowledge, we hope to identify immune modulators or adjuvants that would aid in their immune response to vaccines and help protect them from disease. This work is done in close collaboration with several national and international research centres through large clinical trials. Our lab uses state-of-the-art technology (high-throughput flow cytometry, multiplex ELISA, real-time PCR, SNP genotyping, microarrays, etc.) to get the most information from very small samples. Part of this also requires a solid investment into development of optimal bioinformatics tools, and we are part of an international group focused on this important task. Parallel to the human descriptive studies, we are developing a vaccine platform in mice on which we can test our vaccines and define the exact molecular mechanisms at work. For example, we use genetically altered strains of Listeria monocytogenes to target our vaccines to only those cells we want to infect, to then deliver its vaccine antigen, induce the desired immune response, and disappear—all without causing any harm to the newborn. Our preliminary data gives us great hope that our final goal is within reach.
Sugar molecules attached to proteins expressed at the cell surface are increasingly recognized as playing an important role in the control of cell-cell interaction. Specific oligosaccharides can be recognized by sugar binding proteins (so called lectins) and this interaction has the potential to control how a cell interacts with other cells. Dr. Ziltener is studying the enzymes, “glycosyltransferases” that allow formation of oligosaccharide groups made from sugars such as sialic acid, fucose, galactose and N-acetylglucosamine to form ligands for selectins. Expression of selectin ligands for instance on cells of the immune system is required for these cells to migrate to a site of inflammation, leave the blood vessel and migrate into the tissue where they then participate in the immune response to e.g. a pathogen. Understanding the mechanisms that control the activities of glycosyltransferases that lead to formation of selectin ligands will thus lead to a better understanding of processes that control migration of cells of the immune system to sites of inflammation.
In diabetes mellitus the pancreas’ insulin-producing beta cells have impaired function or are destroyed, resulting in deficient insulin secretion. This leads to high blood glucose levels and later complications, including kidney disease and blindness. In type 1 (juvenile onset) diabetes the patient’s own immune system kills the beta cells. In type 2 (adult onset) diabetes, the body is less sensitive to insulin produced, and the beta cells cannot secrete enough insulin to compensate. Over time, insulin secretion declines, probably due to a progressive loss of beta cells from the toxic effects of elevated blood glucose as well as the accumulation of protein-containing deposits called islet amyloid. Dr. Verchere’s lab is trying to understand how beta cells normally function and why they are dysfunctional and/or are destroyed in both types of diabetes. They hope to devise new ways to protect beta cells, thereby slowing or preventing disease onset, and to enhance beta cell survival following transplantation of pancreatic islets into diabetic patients.
Dr. Cote’s research concentrates on the mitochondrial toxicity of drugs, primarily antiretroviral drugs used in HIV therapy. HIV combination therapy has significantly decreased mortality in the HIV infected population. However, treatment is life-long and as HIV infected individuals survive longer, the toxicity of the drugs and the serious side effects associated can cause of morbidity, non-adherence to prescribed therapy and mortality. HIV drugs can increase mitochondrial DNA (mtDNA) depletion/mutation/deletion through pressure on polymerase gamma, the enzyme responsible for mtDNA replication. In addition, some HIV drugs can inhibit telomerase, the enzyme complex elongating telomeric DNA. MtDNA damage and telomere shortening have been associated with diseases and aging.
Disorders of cholesterol metabolism underlie several human diseases, including heart disease and stroke. Recently, cholesterol metabolism has been recognized to play a major role in the pathogenesis of Alzheimer’s disease. Dr. Wellington’s laboratory studies genes that regulate cholesterol metabolism throughout the body, and as such they are at the interface between dementia and cardiovascular research.
Dr. Rajcan-Separovic’s laboratory studies chromosomes and their changes in a variety of human diseases such as intellectual disability, autism, cancer and pregnancy loss. We are especially interested in tiny chromosomal changes that are invisible under the microscope. We use a recently developed technology of genomic microarrays, which allows detection of microscopically invisible (or sub-microscopic) changes. The identification and accurate description of these small chromosomal changes will help the identification of new genetic causes of common human diseases.
Recent evidence suggests that a mother’s diet during pregnancy can influence the development of cardiovascular disease (CVD) risk factors in their adult children. Currently my research focuses on determining how this occurs. Dr. Devlin speculates that maternal diet during pregnancy can influence gene expression in children through epigenetic processes, defined as heritable changes in gene expression that occur without a change in the DNA sequence of the gene. Dr. Devlin is conducting studies in mice to determine the roles of prenatal and early postnatal diet and the role of epigenetic processes in the development of CVD, and am addressing the questions: if diet during adult life can change epigenetic processes, what happens to offspring exposed early in development to a similar nutrient insult, and are there consequences later in life? Overall determining how diet and epigenetic processes contribute to CVD will aid in the development of early screening tools for at-risk children, and novel therapeutic targets for prevention and treatment of CVD.
Dr. Graham Sinclair
Biochemical Genetics, Inborn errors of metabolism, Newborn screening
Dr. Sinclair’s research interests focus on the laboratory diagnosis and pathophysiology of inborn errors of metabolism. This work is primarily translational in nature, using mass spectrometry approaches to apply basic research findings to the diagnosis, screening, and monitoring of patients with metabolic disorders. This work has included proteomic studies of murine models of lysosomal storage disorders for biomarker discovery and validation, along with population genetics studies of fatty acid oxidation variants and their potential clinical impact. Finally, the expansion of Newborn Metabolic screening in BC has provided a number of opportunities for the development of improved disease biomarkers and mass spectrometry-based diagnostic testing for rare diseases in BC.