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Updated: December 3, 2012
2013 MEDI 502 HOST LAB SELECTION
MEDI 502 is an interdivisional laboratory research course that is required of all new graduate
students in the Experimental Medicine Program. The format of this course creates a unique
opportunity for graduate students to become acquainted with research topics and techniques
outside the scope of their own laboratory or of the Division within which the students are
enrolled. This benefits not only the students, but fosters interactions between faculty and
students in all Divisions of the Department of Medicine. This is also a course in which the
student must take most of the responsibility for arranging the laboratory rotations and deciding
on a grant proposal topic. The format allows a great deal of flexibility, as well as responsibility,
on the part of the student. The two main goals are to be able to present a research seminar, and to
prepare a research proposal, both of which are essential for any future careers in biomedical
research.
Laboratory rotations:
Period 1:
Period 2:
January 3 to February 14, 2013
February 19 to March 19, 2013
For each period, students must arrange research rotations in the laboratories of faculty members
in the Experimental Medicine Program, in two divisions that are distinct from the division in
which the student is working. At least one of the rotations should be outside of the site at which
the student is working. The time allotted to each research rotation has generally been at least 4
full work days over each period, but any arrangement can be made between the individual
student and faculty. In no case should the amount of time be less than four days, but the upper
limit will depend on the student and supervisor's interests and time availability. During this time,
the student will be exposed to the theory and techniques being used in one or more projects of the
host laboratory. It is expected that the student will interact with multiple members of the host
laboratory, and wherever possible, participate in experimental procedures.
Introductory Meeting: There will be an introductory meeting of the class on Thursday, January
3, 2013, 3:00 – 5:00 pm, at the Eye Care Centre Auditorium, 2550 Willow Street. This meeting
will be conducted by the course coordinator, and the elements of a good scientific presentation
will be discussed.
Seminar presentations: Seminar presentations by students (approximately 20 minutes) based
on the ongoing research in the first host laboratory. The presentations will be made at the
following dates and times:
Date
Time
Location
Thursday, January 3
3:00 – 5:00 pm
Eye Care Centre Auditorium
Thursday, February 14
3:00 – 5:00 pm
10206, 10th Floor, DHCC
Tuesday, February 19
3:00 – 5:00 pm
Eye Care Centre Auditorium
Thursday, February 21
3:00 – 5:00 pm
Eye Care Centre Auditorium
Tuesday, February 26
3:00 – 5:00 pm
Eye Care Centre Auditorium
Thursday, February 28
3:00 – 5:00 pm
Eye Care Centre Auditorium
Updated: December 3, 2012
Tuesday, March 5
3:00 – 5:00 pm
Eye Care Centre Auditorium
Thursday, March 7
3:00 – 5:00 pm
Eye Care Centre Auditorium
Tuesday, March 12
3:00 – 5:00 pm
Eye Care Centre Auditorium
Thursday, March 28
3:00 – 5:00 pm
10206
Grant proposal: A formal, CIHR-style grant proposal will form a major part of the mark. The
student will complete this using CIHR’s forms for research and budget modules and Common
CV for CV module. Design of this proposal should be done in consultation with faculty
members from the host labs, and should incorporate elements of the work that the student was
exposed to during the laboratory rotations, but can also incorporate some of the student's own
research interests. A technical abstract will be due midnight March 4, 2013. This will be
reviewed by the Course Coordinators to help direct development of the proposal. Electronic
submission of proposals will be due midnight April 24, 2013 (last day of exam week). On the
last meeting day (Mar 28) another presentation describing the design and preparation of the grant
proposals will be given by the course coordinator and the floor will be open to discussion.
Assessment of the student's performance:
a)
b)
c)
d)
e)
Evaluations by the principle investigators in both host laboratories (20%).
Evaluation of the seminar presentation, by the course co-ordinator (25%).
Grant proposal (45%).
Attendance (10%) ≤1 absence=10%, 2 absences=7%, 3 absences=4%, >3 absences=0)
BONUS discussion points (maximum of 3%).
Updated: December 3, 2012
MEDI 502 LABORATORY RESEARCH ROTATION SLOTS
2013
CARDIOLOGY
Cardiac Imaging
Principle Investigator: Dr. G.B. John Mancini
Contact:
Phone:
E-mail:
Eunice Yeoh, VGH Research Pavillion
875-5477
[email protected]
The Cardiac Imaging Research Laboratory is dedicated to determining the structure and function
of arterial beds for the purpose of evaluating effectiveness of therapies designed to promote
vascular health. The laboratory is a pioneer in the application of digital imaging methods to
coronary arteriograms and cardiac ventriculograms. The laboratory has also expanded to
facilitate quantitation of carotid atherosclerosis and endothelial function using brachial
ultrasound techniques and is currently involved in mult-centre trials using cardiac computed
tomography. The largest ongoing projects are world-wide clinical trials requiring our laboratory
to undertake computerized image analyses. These trials are investigating the optimal initial
approach for management of coronary disease (i.e. percutaneous coronary intervention versus
drug treatment) and whether prognosis can be improved by stenting previously occluded
coronary arteries. These trials are funded by the NIH, MRC and the VA Clinical Trials Program.
Critical Care
Principal Investigator: Dr. Keith R. Walley, M.D. (University of Manitoba, 1981)
Telephone: 806-8136
Fax:
806-8351
E-mail:
[email protected]
The focus of this laboratory is to:

Investigate the mechanism of decreased cardiac function during severe infections.

Investigate the mechanism of impaired oxygen consumption during severe infections.

Understand the mechanisms that lead to organ dysfunction (lung and gut) during severe
infections.

Techniques in use include isolation and culture of cardiac myocytes and leukocytes,
ELISA, RT-PCR, caspase activity assays, EMSA, morphometric analysis of tissue
samples, and 3D deconvolution microscopy.
Updated: December 3, 2012
Cardiovascular Physiology
Principal Investigator: Dr. Darren E. R. Warburton
Telephone: (604) 822-1337
Email: [email protected]
Internet address: http://www.hkin.educ.ubc.ca
The Cardiovascular Physiology and Rehabilitation Laboratory evaluates the effects of
improvements in cardiovascular function on the health status and Quality of Life of children,
adolescents, adults, the elderly and patients with chronic disease and/or disability (including
individuals with heart disease, organ transplantation, and spinal cord injury). We also specialize
in the evaluation and training of high performance able-bodied and disabled athletes.
Our facility houses a mass spectrometer (Amis 2000), an applanation tonometer, a transcranial
Doppler system, a stand-alone 2-D Doppler cardiac ultrasound (Sonos 2500 Hewlett-Parkard),
two impedance cardiography systems, a beat-by-beat blood pressure monitor (Finapres,
Ohmeda), a near-infrared spectrophotometer (Niro 300, Hammamatsu), two cardiac stress testing
systems (including two 12 lead ECG and treadmill systems), two metabolic carts (including a
portable metabolic cart), a telemetric electrocardiography (3-lead) system, several pulse
oximeters, heart rate variability analysis equipment, eight interactive video game training systems
(GameBikeTM, Cateye), ten Monark rehabilitation cycle ergometers, three electronically braked
cycle (arm and leg) ergometers, and an automated defibrillator. This equipment allows for the
complete evaluation of left ventricular function, diffusion capacity, oxygen kinetics, endothelial
function, heart rate variability, and cerebral and skeletal muscle oxygenation and blood flow
during resting and/or exercise conditions.
Nutritional Epigenomics and Cardiometabolic disease
Principal Investigator: Dr Angela M Devlin, PhD
Division of Endocrinology, Department of Paediatrics, Child & Family Research Institute
Telephone: 604.875.2000 x 5378
Fax:
604.875.3597
E-mail:
[email protected]
My laboratory is focused on investigating:

the interactions of dietary factors with epigenetic processes and development of
cardiometabolic risk factors (eg obesity)

the molecular mechanisms contributing to vascular dysfunction associated with obesity,
hyperhomocysteinemia

metabolic programming and risk for cardiovascular disease
Techniques include: genotyping, gene expression, immunoblots, DNA methylation analysis
(Pyrosequencing), chromatin immunoprecipitation, cell culture.
Updated: December 3, 2012
DERMATOLOGY
Molecular mechanisms of cancer development
Principal Investigator: Dr. Gang Li M.Sc. (University of British Columbia 1989), Ph.D.
(University of British Columbia 1992)
Telephone: 875-5826
Fax:
875-4497
E-mail:
[email protected]
The following projects are the main focus of this laboratory:

Biological functions of ING tumor suppressors including UV stress response, PCNAmonoubiquitination and S phase recovery, cell cycle regulation, apoptosis and DNA repair;

Signalling pathways of tumor cell migration, invasion, angiogenesis;

identification of novel prognostic markers and therapeutic targets.
Molecular Markers of Skin Cancer and Skin Inflammation
Principal Investigator: Youwen Zhou, MD, Ph D, Assistant Professor
MD. 1995, University of Toronto, Ph.D. 1990, State University of New York
Molecular Medicine Lab (MML) & Chieng Genomics Centre
Department of Dermatology and Skin Science
Tel: 604-875-4747
Fax: 604-873-9919
Email: [email protected]
The MML Lab aims to translate the latest advances in biomarker research into clinical
applications. The experimental approaches used include expression genomics, next generation
sequencing, molecular genetics techniques, and retroviral mediated gene transfer.
Current projects include:
(1). Pathogenic significance and therapeutic targeting of extracellular matrix molecules in
metastatic melanoma
(2). Novel diagnostic and prognostic markers for cutaneous T cell lymphoma
(3). Mutation identification of hereditary primary hyperhidrosis
(4). Novel anti-inflammatory agents for chronic inflammatory skin diseases
Updated: December 3, 2012
Skin appendages in health and disease
Principal Investigator: Dr. Kevin McElwee, Ph.D. (University of Dundee, 1996)
Telephone:
Fax:
E-mail:
Internet:
604 875-4111 ext. 63908
604 875-4376
[email protected]
www.hairlaboratory.org
The following projects are the main focus of this laboratory:

The mechanisms of hair loss involved in alopecia areata and scarring alopecias (suspected
autoimmune alopecias).

Immune privilege in hair follicles and its functional role.

The relationship of skin cancer to hair follicle biology.

The role of chemokines in the development and growth of basal cell carcinomas.
GASTROENTEROLOGY DIVISION
Lipoprotein Metabolism
Principal Investigator: Urs Steinbrecher M.D. (University of Alberta, 1976)
Telephone: 875-5039 (office) 875-4451 (lab)
Fax:
875-5447
E-mail:
[email protected]
The focus of this laboratory is on the pathogenesis of atherosclerosis and, in particular, on
defining the role of oxidized low density lipoprotein (oxLDL) in the initiation and progression of
this disease. Current projects involve characterization of the functional role of receptors for
oxidized LDL, identification of signalling pathways in macrophages that are activated by
oxidized LDL, identification of components of oxidized LDL that are responsible for signal
activation, and characterization of the functional consequences of oxLDL-induced signal
transduction. Techniques in use include cell culture, lipoprotein isolation, lipid analysis by
enzymatic and chromatographic methods (TLC, HPLC, GC), protein purification, assays of
activity of various enzymes involved in lipid metabolism and cell signalling, immunoblotting,
immunoassays, fluorescence microscopy of living or fixed cells, electrophoresis, lipoprotein
turnover studies in vivo, Northern blots, Southern blots, PCR, and studies in transgenic animals.
Updated: December 3, 2012
IMMUNOLOGY
Cellular Immunology/Gene Expression Profiling Laboratory
Principal Investigator: Dr. Cheryl D. Helgason, Ph.D.
Cancer Endocrinology Dept., B.C. Cancer Research Center
Telephone: (604) 877-6098 ext. 3007
Fax: (604) 877-6011
E-mail: [email protected]
The primary research area in this laboratory involves examining the role of dendritic cells (DC)
and regulatory T (Tr) cells in initiation and control of cellular immune responses. We utilize both
transgenic and knock-out mouse models of disease to understand what role these two cell types
play in the initiation and progression of autoimmunity and prostate cancer. Techniques utilized in
these studies include isolation of lymphoid tissues, magnetic purification of sub-populations of
immune cells, flow cytometry, cell culture, and various types of functional analyses (i.e. T cell
proliferation assays).
A second area of investigation involves the use of serial analysis of gene expression (SAGE) and
Affymetrix array analysis to determine gene expression profiles during mouse embryonic
development and during the in vitro differentiation of murine embryonic stem (ES) cells
respectively. The first project involves the dissection of selected tissues from mouse embryos at
critical stages during organ/tissue development. The second involves the culture and
differentiation of ES cells. Data analysis requires the use of a number of bioinformatic tools (i.e.
GeneSpring; DiscoverySpace) to generate lists of candidate genes that may be involved in the
biological processes of interest (i.e. pancreas organogenesis). Validation studies involve
techniques such as quantititative RT-PCR, in situ hybridization, and ultimately inhibition and/or
over-expression studies.
Innate Immunity
Principal Investigator: Dr. Ted Steiner (M.D. Duke Univ., 1992)
Telephone: 875-4111 x 68492
Fax: 875-4013
E-mail: [email protected]
Areas of active research include basic mechanisms of flagellin regulation by Toll-like receptor 5
and downstream signaling pathways; Role of anti-flagellin immune responses in colitis; Effects
of stress signals on TLR responses in intestinal epithelial cells.
Updated: December 3, 2012
Innate Immunity
Principal Investigator: Zakaria Hmama, PhD
UBC-Division of Infectious Diseases
D458, Heather Pavilion East
2733 Heather ST, Vancouver
V5Z 3J5, British Columbia, Canada
Email: [email protected]
http://www.id.med.ubc.ca/Faculty/Faculty_Hmama.htm
Research in this lab is concerned with molecular and subcellular mechanisms of Tuberculosis
pathogenesis with a particular focus on intracellular persistence of M. tuberculosis in the
macrophage and down-modulation of antigen presentation.
Methodologies & Techniques: Cloning, Transformation, Transfection, Protein Expression and
Purification, SDS-PAGE/WB, FACS, Confocal, ELISA.
Neonatal Immunology
Principal Investigator: Pascal Lavoie, MD PhD FRCPC
Child & Family Research Institute
Telephone:
875-2000 x7318 (office) 875-2000 x6705 (lab)
Fax:
875-3106
E-mail: [email protected]
This laboratory studies on innate and adaptive immune defenses in neonates, particularly those
born early in gestation. One main project focuses on understanding why newborns are highly
susceptible to infections. This is achieved specifically by investigating mechanisms for
inflammatory Toll-like receptor-mediated hypo-responses in babies born prematurely, using cell
immunology, flow cytometry and molecular biology techniques (Q-PCR gene expression,
western blots). Toll-like receptors are family of molecules playing a critical role in first-line
innate immune defenses, particularly in neonates.
A second main project focuses on neonatal invariant Natural Killer T cells and their unique
phenotype expressed in neonatal life. T lymphocytes play a central role in adaptive immune
defenses by "orchestrating" the activity of other cells such as the antibody-producing B
lymphocytes, or by killing virally-infected cells directly. NKT cells are of main interest because
of their potential in regulating excessive inflammatory responses from other innate (i.e. first line)
immune cell types. At the moment, our efforts in this area are focused on understanding how
NKT cells emerge in neonates, with particular emphasis on receptor regulating proliferation and
maintenance of this highly specialized immunological compartment.
Updated: December 3, 2012
Clinical Immunology Laboratory
Principal Investigator: Dr. Paul Keown
Telephone: (604) 875-5555 (ext. 62042)
Fax: (604) 875-4709
E-mail:
[email protected]
The clinical immunology laboratory is located at the Vancouver General Hospital and serves as a
central laboratory for the number of UBC programs, including bone marrow transplantation,
solid organ transplantation, autoimmunity and genetic disorders. It comprises four principal
divisions:
1) Histocompatibility and immunogenetics (HLA typing, donor-recipient cross-matching,
paternity testing, gene polymorphism using robotics DNA extraction, PCR, automated
gene sequencing, fragment analysis, liquid bead-based reverse SSOP (Sequence Specific
Oligonucleotide Probe)
2) Immunologic monitoring (T-cells, B-cells and antibody monitoring using Flow
cytometry and solid-phase Luminex assay)
3) Immunotherapeutics (clinical trial-oriented research that involves
pharmacokinetics and pharmacodynamics of immunosuppressive drugs)
study
of
4) Autoimmunity (auto-antibody detection using ELISA technique)
Cellular regulation of peripheral tolerance
Principal Investigator: Dr. Megan Levings
Phone:
Fax:
E-mail:
875-4111 ext 66742
875-4497
[email protected]
Research in my laboratory is focused on a novel subset of CD4+ T cells, termed T regulatory (Tr)
cells, which control immune homeostasis. Current work is focused on determining how Tr cells
differ from normal CD4+ T cells at both the biochemical and molecular phenotype, and
elucidating their role in transplantation tolerance, cancer and infectious diseases. An immediate
goal is to identify novel Tr-specific molecules which may reveal their mechanism of action
and/or be used as a tool to isolate and track Tr cells more efficiently. A long term goal is to a)
develop methods to generate Tr cells in vitro for use as a cellular therapy to replace standard
immunosuppression in the context of organ transplantation; and b) identify ways to deplete Tr
cells in order to increase the immune response to cancer and chronic infectious diseases.
Signal Transduction in Cell Adhesion and Migration
Updated: December 3, 2012
Principal Investigator: Dr C. James Lim, PhD
Assistant Professor, UBC Department of Pediatrics
Scientist, Child and Family Research Institute
Email: [email protected]
Tel: 604 875 2000 ext. 4795
http://www.cfri.ca/our_research/researchers/search_researchers/researcher_detail.asp?ID=360
Research Interest:
Integrins in cell adhesion and migration, protein-protein interactions, protein phosphorylation and
kinase signaling.
My lab research is aimed at understanding the molecular mechanisms governing cell adhesion
and motility, in particular those involving white blood cell function in normal as well as in
pathologic outcomes, including cancer and autoimmunity. Circulating white blood cells represent
the immune system’s frontline defence against infection. The successful and accurate targeting of
white blood cells to inflamed tissues is facilitated by cell adhesion receptor proteins expressed on
the surface of these cells. However, aberrant function of these receptor proteins and the cellular
signals that regulate them can lead to diseases of the immune system, including leukemia,
lymphoma and autoimmunity. Ongoing research is focused on understanding the differences in
cellular signalling between healthy and diseased cells in order to explore and evaluate novel
signalling targets for therapeutic intervention in blood diseases. My laboratory employs a multidisciplinary approach that encompasses cell biology, protein biochemistry, molecular biology and
immunology.
Signal Transduction
Principal Investigator: Dr. Alice Mui
Phone:
Fax:
E-mail:
875-5555 ext 62242
875-4497
[email protected]
The cytokine interleukin-10 (IL-10) is a key regulator of both innate and acquired immunity with
activities ranging from co-stimulation of thymocytes, mast cells and B-cells to inhibition of
macrophage, NK, dendritic and T-cell function. Produced by activated B-cells, keratinocytes,
monocytes and macrophages, IL-10 was initially detected as a Th2 cell product that inhibited the
proliferation, development and function of Th1 cells. The molecular cloning of IL-10 and
subsequent studies utilizing recombinant cytokine revealed that although IL-10 exerted direct
effects on T-cells, its major site of action was the activated macrophage. Research interests in
my lab focus on the IL-10 regulation of macrophage and T cell activation, IL-10 induced gene
expression, and the role of STAT transcription factors in signal transduction.
Updated: December 3, 2012
INFECTIOUS DISEASES DIVISION
Bioinformatics Studies of Bacterial Genomes.
Principal Investigator: Dr. Artem Cherkasov
Telephone: 875-4111 x 68541
Fax:
875-4013
E-mail:
[email protected]
My group's research is focused on bioinformatics and molecular modeling methods and
techniques for studying genomes and proteomes of pathogenic organisms.
Studies are currently underway on:
1.
Development of new bioinformatics methods for identification of pathogenic virulence
factor proteins.
2.
'In silico' development of new antimicrobial drugs.
3.
Development of reliability analysis approach for the area of structural genomics.
Innate Immunity
Principal Investigator: Dr. Neil E. Reiner A.B. (Oberlin College, 1970), M.D. (Case-Western
Reserve University, 1974)
Telephone:
Fax:
E-mail:
875-4011
875-4013
[email protected]
Areas of active research include the regulation of macrophage activation, monocyte gene
expression, and the role of protein kinases and phosphoproteins in signal transduction for
monocyte activation, phagosome biogenesis.
Molecular Genetics of Tuberculosis
Principle Investigator: Dr. Yossef Av-Gay
Telephone: 875-4588
Fax:
875-4013
E-mail:
[email protected]
Research interests are molecular genetics of tuberculosis, identification and validation of new
molecular targets for drug therapy. We focus our research on the metabolism of bacterial
pathogens inside their hosts. In my lab, we employ advanced approaches such as gene knockouts
and biochemical analysis of proteins to search for new drug targets against TB.
Updated: December 3, 2012
MEDICAL BIOPHYSICS DEPARTMENT, BCCRC
DNA Damage and Repair
Principal Investigator: Peggy L. Olive, Ph.D. (Biochemistry, McMaster, 1976)
Phone: 604-675-8031
Fax: 604-674-8049
e-mail: [email protected]
A major goal of this lab is the development of methods to measure DNA damage and repair to
use as indicators of tumor and normal cell response to ionizing radiation and cytotoxic drugs.
The comet assay, a single cell gel electrophoresis method, was developed in this lab to detect a
variety of types of DNA damage in individual cells. DNA repair complexes are also being
measured using both flow cytometry and quantitative image cytometry. Retention of DNA repair
complexes for long times after treatment is associated with a variety of DNA repair deficiencies,
genomic instability, and cell death. DNA damage is being correlated with clonogenic cell
survival and other endpoints using cultured cell lines, multicell tumor spheroids in culture,
tumors in mice, and clinical biopsies.
MOLECULAR MEDICINE
Inflammation in Diabetes Research Lab
Principal Investigator: Dr. Jan Ehses
Department of Surgery, Division of General Surgery
Phone:
604-875-2000 x4910
Fax:
604-875-2373
Email:
[email protected]
Web:
www.ehseslab.com
Research in my laboratory is focused on immunometabolism; how the immune system can
regulate whole body metabolism and therefore impact on the progression of diseases such as
obesity and diabetes. Obesity and type 2 diabetes affect greater than 300 million people
worldwide. It is now appreciated that both obesity and type 2 diabetes are chronic inflammatory
diseases. We use rodent models of disease and genetic knockout mice, and perform both complex
in vivo phenotyping of disease progression in addition to in vitro work on the cross-talk of
macrophages and cytokines with endocrine cells of the pancreatic islet. Novel findings will also
be evaluated in human islets. Currently, work in the lab is focused on 3 main topics: 1)
Elucidation of the role of regulatory macrophages in islet inflammation and type 2 diabetes; 2)
The role of inflammation as a mediator of alpha cell dysfunction in type 2 diabetes (specifically,
alpha cell gp130 receptor signaling); 3) The role of TLR2 and TLR4 in beta cell dysfunction and
type 2 diabetes. Our long-term goal is to identify novel immunomodulatory therapies that will be
beneficial for the treatment of obesity and diabetes.
Updated: December 3, 2012
Centre for Blood Research
Principle Investigator: Dr. Ed Conway
Contact:
Ed Conway, Centre for Blood Research, Life Sciences Centre, UBC
Phone:
604-822 4252
Email:
[email protected]
Major research projects in my lab:
 To biochemically characterize novel interactions between the complement activation and
coagulation systems.
 To assess the physiologic role of the mesenchymal cell surface glycoprotein, CD248, in
models of inflammation and cell proliferation.
Investigative approaches utilise a wide range of technologies, including molecular and cellular
biology, biochemistry, and transgenic mouse models.
HEMATOPOIESIS / DEVELOPMENT
Investigator: Dr. Kelly McNagny, PhD. (U. of Alabama at Birmingham) Postdoc. (European
Molecular Biology Laboratory)
Phone: 822 7824
Email: [email protected]
We are interested in the mechanisms governing hematopoietic cell differentiation and their
homing and migration. Recently we have focused on the CD34 family of adhesion / antiadhesion molecules. Deletion and overexpression of these molecules in cell culture or in mice
suggests that they normally act as “molecular Teflon” to prevent in appropriate cell adhesion.
We are now exploring the elements that govern the expression, and distribution of these
molecules.
In addition, we are developing an number of new transgenic mouse lines that should allow the
assessment of homing and differentiation of hematopoietic cells in real time in vivo.
Immunology
Investigator: Dr. John Schrader Ph.D., M.B.B.S. (University of Adelaide, 1969), B.Med.Sc.
(Hons., University of Melbourne, 1972), Ph.D. (University of Melbourne, 1975)
Updated: December 3, 2012
Telephone: 822-7822
E-mail:
[email protected]
Dr. Schrader's laboratory is studying two key classes of molecules produced by the cells of the
immune system, cytokines and antibodies. One series of studies are investigating the molecular
mechanism through which cytokines exert their effects on the growth and differentiation of cells.
This work may lead to new approaches to the management of diseases such as leukemia, asthma
and arthritis. Another series are generating monoclonal antibodies or engineered fragments of
antibodies, with the aim of using them as therapeutic agents or as novel research tools. The
experimental approaches integrate cellular, biochemical and molecular techniques.
Oncogenomics
Investigator: Dr. Sandra E. Dunn, Ph.D.
Laboratory for Oncogenomic Research, Dept. of Paediatrics, BCRICWH
[email protected]
tel. 604-875-200 ext. 6015 fax 604-875-3471
The proposed research is directed at improving the treatment of women and children with cancer
by developing targeted therapies to reduce relapse. Our studies indicate that tumor-initiating
cells (TIC) may be at the root of this problem. TIC are resistant to traditional chemotherapeutic
agents and re-initiate tumor formation. Importantly, we discovered that YB-1 imparts drug
resistance by inducing a cassette of TIC genes and causes recalcitrance to agents commonly used
in the clinic such as Paclitaxel, Herceptin and Temozolomide. We plan to explore the precise
mechanisms whereby YB-1 conveys resistance using antibody signaling arrays, chromatinimmunoprecipitation followed by sequencing, coupled with molecular and cellular biology
approaches. Building on our observation that p90 ribosomal S6 kinase (RSK) phosphorylates and
thereby activates YB-1 we propose to develop RSK inhibitors. We recently synthesized the RSK
inhibitor, BI-D1870, and show that it potently inhibits YB-1 phosphorylation (IC50=60 nM) yet
we need to further optimize the compound in order to improve cellular delivery. Further, we are
exploring the possibility that there are off-patent drugs that inhibit RSK to expedite the delivery
of new treatment options to patients. Beyond YB-1, we will validate the potential for polo-like
kinase-1 (PLK1) because we find it is essential for the growth of a wide range of cancer types
following a large small interfering RNA (siRNA) screen. Notably, blocking PLK1 with either
siRNA or a small molecule suppresses tumor growth by ~90%. Small molecules toward PLK
have advanced through Phase I clinical trials in adults with limited side-effects therefore these
agents may be available in the near future to children with cancer. Our plan is to inhibit PLK1 in
models of pediatric GBM in vitro, in mice as well as by treating primary tumor explants from
patients. We will extend our preliminary data showing that PLK/RSK and YB-1 facilitate G2/M
cell cycle progression by forming a complex that is essential for spindle pole assembly. Our goal
is to eliminate tumor cells that have previously gone "under the radar" of conventional therapies
as a means of reducing relapse.
NEPHROLOGY DIVISION
Updated: December 3, 2012
Epithelial Transport and Membrane Biology
Principle Investigator: Dr. Gary Quamme D.V.M. (University of Saskatchewan, 1970),
Ph.D. (McGill University, 1974)
Telephone: 822-7156
Fax:
822-7897
E-mail:
[email protected]
Research interests include the investigation of epithelial transport and regulatory controls, with
specific interests in Ca2+, Mg2+ and phosphate. On-going research projects include the
determination of intracellular Ca2+, Mg2+ and Na+ with microfluorescent spectrometry. Cell
models include single established cell culture lines or RNA injected Xenopus oocytes. The
major research interests include molecular biological description of transport through the use of
expression cloning, homology-based strategies, and differential display approaches. The
objective is to clone novel transporters and assess their presence and control under physiological
and pathological conditions. It is expected that the student would select one of the on-going
projects and will, over the course of the class, obtain the theoretical background and technical
ability to carry out experiments with these methodological approaches.
NEUROLOGY DIVISION
Neurology
Principal Investigator: Dr. Seung U. Kim M.D. (Seoul University, 1960), Ph.D. (Kyoto
University, 1965)
Telephone: 822-7158
Fax:
822-7897
E-mail:
[email protected]
Research in Dr. Kim's laboratory centres on the tissue culture studies of neurons and glial cells
isolated from human and other mammalian nervous system tissues. Oligodendrocytes, cells
which produce and maintain central myelin and myelin itself, are primary targets of possible
infectious or immunopathological reactions in patients with multiple sclerosis. Human and
bovine oligodendrocytes are currently purified and grown in culture for the purpose of studying
the basic morphological, physiological, metabolic and immunological properties of the cell type.
In addition, putative growth factors that can stimulate proliferation and differentiation of
oligodendrocytes are sought and screened in the culture systems.
Immunology and Neurology
Investigator: Dr. Joel Oger, M.D. (France, 1970), C.E.S. Neurologie (France, 1976) FRCPC
(Canada 1983)
Updated: December 3, 2012
Telephone: 604-822-7548
E-mail:
[email protected]
Research in Dr. Oger's lab focuses on in vitro techniques of cellular immunity applied to
neurological diseases such as Multiple Sclerosis, HTLV-1 Associated Myelopathy and
Myasthenia Gravis. Blood lymphocytes are isolated and set up in different functional assays
including: IgG and Acetylcholine receptor antibody secretion following pokeweed mitogen
stimulation, suppression of DNA synthesis or of B cell function, induction of suppression by
mitogens or autologous mixed lymphocyte reaction. These results are correlated with
enumeration of lymphocyte subpopulations with special emphasis on T suppressor/inducers, T
helper/inducers and activation of T lymphocytes. Using fluorescent activated cell sorter we also
do cell enumeration.
Further work is on-going on antibody measurements and the auto-immune diseases they
generate: Acetycholine receptor antibodies (Myasthenia gravis) neutralizing antibodies to
interferon in treated MS patients, Antibodies to MuSK in AchrAb negative myasthenia gravis
and anti-Aquaporine-4 antibodies in Neuromyelitis Optica.
Neurotransmitters
Investigator: Yu Tian Wang, MD, PhD, Professor and Chair in Stroke Research, Department of
Medicine, Division of Neurology and Brain Res. Center
Tel: 822-0398
Fax: 822-7170
e-mail: [email protected]
Research interests:
Glutamate and GABAA receptors are two principal neurotransmitter receptors, which mediate
excitatory and inhibitory synaptic transmission, respectively, in the brain and these receptors play
a crucial role in both brain function and dysfunction. My colleagues and I are interested in
understanding molecular mechanisms responsible for the intracellular trafficking and plasma
membrane targeting of these receptors, and investigating the manner by which these mechanisms
may be altered in CNS disease processes. The goal is, ultimately, to be able to treat central
nervous disorders, such as cerebral ischemia and epilepsy, by designing new therapeutics which
specifically target these receptors and their pathways.
Signal Transduction
Principal Investigator: Dr. Steven Pelech B.Sc. (Hons., University of British Columbia,
1979), Ph.D. (University of British Columbia, 1982).
Telephone: 604-218-2019
E-mail:
[email protected]
Updated: December 3, 2012
Dr. Pelech’s laboratory focuses on the role of protein kinases in the regulation of cell cycle
progression and apoptosis. In eukaryotes, essentially all cellular functions are tightly regulated
by complex networks of protein kinases and other interacting proteins. At least 518 protein
kinases are encoded by the human genome, but less than a third of these are well characterized.
The importance of a thorough understanding of the architecture and operation of protein kinase
cascades is being recognized with the discovery that as many as 400 human diseases, including
cancer, diabetes, cardiovascular and neurological disorders, are linked with defective signal
transduction. At the same time, there has been a strong trend for researchers world-wide to
correlate many normal and pathological cellular processes with a relatively small number of
protein kinases.
Dr. Pelech's laboratory has been developing methodologies to track the phosphorylation states
and expression levels of hundreds of distinct protein kinases and their substrates simultaneously.
One technique involves Western blotting with panels of mixed antibodies for different protein
kinases and phospho-sites. The model systems with which these analyses are being conducted
include: 1) meiotic maturation of seastar and frog oocytes; 2) mitogenic and stress stimulation of
human tumour cells; and 3) brain and spinal cord preparations from patients that have died from
ALS, Alzheimers disease, and multiple sclerosis. The techniques used in Dr. Pelech's laboratory
include those for enzyme purification and characterization (e.g. column chromatography,
enzyme assays, gel electrophoresis), gene cloning, sequencing and expression in bacteria,
immunological
analyses
(e.g.
Western
blotting,
immunoprecipitation,
ELISA,
immunocytochemistry), and cell biology (e.g. cell culture, cell microinjection).
RESPIRATORY MEDICINE DIVISION
Signal Transduction
Principal Investigator: Dr. Vincent Duronio (Ph.D., U. Western Ontario, 1984)
Telephone: 875-4707
Fax:
875-4497
E-mail:
[email protected]
Dr. Duronio's lab is interested in the signal transduction mechanisms downstream of hemopoietic
growth and differentiation factors, and how the specific signals regulate cellular responses to
these factors. The model systems are both human and murine cell lines, as well as blood cells
isolated from donors. We are examining the activity of protein kinases activated in response to a
number of cytokines, including IL-3, IL-5 and GM-CSF, the receptors for which share a common
beta subunit. One focus is on the regulation of lipid signalling pathways, primarily
phosphatidylinositol 3-kinase (PI 3-kinase) and the numerous proteins that are targets of
phosphorylation by the PI 3-kinase-regulated protein kinase B. The role of PI 3-kinase in cell
regulation, and in particular as a signal that is regulating apoptosis, or programmed cell death, is
a major emphasis. We are investigating several aspects of regulation of Bcl-2 family members
Updated: December 3, 2012
both at the level of message and protein expression and protein phosphorylation. A goal of many
of these studies is to determine how specific signals are regulating differentiation, as well as
survival of cells that are involved in inflammatory responses. Some effort is also being made to
examine selected transciptional events, and regulation of gene expression by cytokines.
Genomics, Proteomics and Metabolomics of the Asthmatic Response to Allergen Challenge
Principal Investigator: Scott Tebbutt, Ph.D.
Telephone: 604-682-2344 ext. 63051
E-mail:
[email protected]
In asthmatic individuals, airway narrowing represents the early phase of the asthmatic response to
allergen inhalation challenge; early phase onset can be detected within ten minutes of allergen
inhalation, reaches a maximum within thirty minutes, and typically resolves within three hours.
In 50-60% of allergic asthmatic adults, the early response is followed by the late phase asthmatic
response, which usually starts between three and four hours after allergen inhalation challenge,
and is characterized by cellular inflammation of the airway, increased lung tissue permeability,
and mucus secretion. Despite tremendous interest, the pathways leading to the late response are
not completely understood.
To more clearly delineate the specific biological pathways involved, we are studying molecular
changes in the peripheral blood of asthmatic individuals who are experiencing these responses.
Understanding these pathways is important for evaluating allergic diseases such as asthma.
In contrast to the more transient isolated early response, development of the late response is
associated with the hallmark inflammatory features of chronic allergic disease.
Pulmonary Research Laboratory
Principal Investigators: Dr. James C. Hogg/Dr. Shizu Hayashi
Telephone: 806-8346
E-mail:
[email protected], [email protected]
We are interested in the role that latent adenovirus (Ad) infections play in the pathogenesis of
obstructive lung disease. We have demonstrate that the DNA of adenovirus E1A is found more
often in lungs of patients with chronic obstructive lung disease (COPD) (1) than in controls
without airways obstruction and that this viral gene is expressed in human lungs (2). In a guinea
pig model of latent Ad infection we have shown that presence of this virus enhances the
inflammatory response in the lung to cigarette smoke exposure (3) and in lung epithelial cells in
vitro that Ad E1A, a transactivator of host genes, enhances the expression of key inflammatory
mediators in response to inflammatory stimuli such as LPS (4-6) and ambient particulate matter
(7). This up-regulation is associated with the activation of the transcription factor NF-B (6-8).
We have applied the in situ PCR technique to identify lung epithelial cells carrying Ad E1A
Updated: December 3, 2012
DNA and are currently investigating the integration of the Ad E1A gene into chromosomes in
human lungs, as well as investigating the molecular mechanism by which E1A regulates the
inflammatory mediator expression using the guinea pig model and lung epithelial cells in culture.
Lung Oncogenesis
Principal Investigators: Dr. Stephen Lam M.D. (University of Toronto, 1974), FRCPC
(Internal Medicine and Respiratory Medicine, 1978)/ Dr. Calum MacAulay
Telephone: 875-4325
Fax:
875-4695
E-mail:
[email protected]
We are interested in the role of early detection and chemoprevention as a lung cancer control
strategy. Lung cancer is the most common cause of cancer death in North America. We have
developed methods to identify individuals harbouring early lung cancer and pre-invasive lesions
using image analysis of sputum cells and an autofluorescence endoscopic method to localize
these lesions in high risk individuals. We are also testing the role of spiral CT to detect early lung
cancer. Clinical trials are being conducted to evaluate the safety and efficacy of chemopreventive
agents such as botanical agents to prevent lung cancer. Intermediate endpoint biomarkers such as
image analysis of bronchial biopsies are used in these Phase II clinical trials. Optical imaging
methods such as confocal microendoscopy and optical coherent tomography are being developed
as non-biopsy methods to determine the pathology grade.
Respiration
Principal Investigator: Dr. Jeremy Road B.Sc. (University of Regina, 1975), M.D.
(University of Saskatchewan, 1977)
Telephone: 875-4122
E-mail:
[email protected]
Dr. Road's research interests include studies on the action of the respiratory muscles and on the
control of breathing. Studies of respiratory muscle function have focused on the diaphragm.
Muscle injury in the respiratory muscles is a newly identified problem of major significance to
breathing. The histochemistry and biochemistry of the inspiratory muscles is being assessed in
conditions including fatigue and injury, immobilization, denervation and exposure to a variety of
drugs. How respiratory muscle fatigue is sensed is under study using single fibre afferent nerve
recordings. Clinical studies are ongoing to parallel these basic physiological studies.
Genetic Susceptibility to Obstructive Lung Diseases
Principal Investigator: Dr. Andrew Sandford Ph.D.
Telephone: 806-9008
Updated: December 3, 2012
Fax:
E-mail:
806-8351
[email protected]
The focus of Dr. Sandford’s research is investigation of the genetic basis of obstructive lung
disease. He is currently studying three large cohorts of individuals. The first cohort contains
infants at high risk for developing allergic diseases and is being used to evaluate the importance
of genetic risk factors for the development of these diseases. The second cohort contains
individuals whose lung function has been followed for five years. Genetic factors that affect the
rate of decline of lung function are being investigated in this cohort. The third cohort contains
individuals who have cystic fibrosis and is being used to determine genetic factors that modulate
pulmonary disease severity.
TERRY FOX LABORATORY
Biology and Regulation of Normal and Malignant Stem Cells
Principal Investigator: Dr. Connie J. Eaves B.Sc. (Biology & Chemistry, Queens University,
1964), M.Sc. (Genetics, Queens University, 1966), Ph.D. (University of Manchester, UK, 1969)
Telephone: 604-877-6070
Fax:
604-877-0712
E-mail:
[email protected]
Experiments in this laboratory and elsewhere have established the existence in adults (both
mouse and man) of primitive hematopoietic stem cells capable of regenerating all myeloid and
lymphoid lineages following the transplantation of these cells into 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 these stem cells using syngeneic (mouse – to - mouse)
and xenogeneic (e.g., human – to – mouse) transplantation strategies. One goal is to define how
the proliferation and differentiation of these cells can be regulated and proactively manipulated
by extrinsic factors. This offers an important approach for therapeutic application as well as for
identifying the intracellular signaling dynamics and downstream molecular targets that determine
whether a stem cell will begin to execute the differentiation programs for which it has acquired
competence (activation of stem cell fate decisions) or whether it will divide and retain this
competence without activating it (self-renewal decisions). We are also attempting to elucidate the
mechanisms by which extrinsic factors control hematopoietic stem cell engraftment changes
during cell cycle transit. Factors with these activities are being identified and their mechanisms
of action studied using purified stem cells, defined culture systems, gene transfer strategies, and
genome-wide gene expression (SAGE and microarray) analysis. Our recent development of a
method for purifying adult murine hematopoietic stem cells to homogeneity has allowed us to
define their unique cell cycle dynamics and independence of self-renewal control from speed of
cell cycle entry. We are now extending these advances to other sources of murine and human
hematopoietic stem cells and hope ultimately to identify a stable stem cell-specific phenotype
signature.
A second goal is to similarly characterize the abnormalities of human chronic myeloid leukemic
Updated: December 3, 2012
stem cells and to develop new models of this disease in mice, sheep and goats reconstituted with
human leukemic stem cells or genetically modified (oncogene-transduced) human and murine
stem cells, and to develop stem cell-based gene therapies using procedures we have optimized for
transducing them at high frequency. These studies are being carried out in collaboration with
other senior scientists in the Terry Fox Laboratory and investigators at Harvard/MIT in Boston,
the Albert Einstein College of Medicine in New York, the University of Nevada at Reno and the
Shanghai Institute of Medical Genetics in China.
A third initiative is focused on extending these approaches to the study of human breast cancer.
Quantitative assays for normal and malignant human breast epithelial stem cells are being
developed and used to purify these cells, to identify their distinguishing features and to define
their normal and perturbed mechanisms of growth regulation using clonal tracking, gene
expression and gene manipulation strategies. 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.
Recently we have also begun to characterize the process by which hematopoietic stem cells
develop from human embryonic stem (ES) cells. These studies have started with a systematic
comparative analysis of the gene expression profile of 8 different human ES lines by microarray
and SAGE and will now be extended to analysis of defined stages of derivative cells using
optimized methods currently under development for generating and isolating these
subpopulations.
Basic and Translational Leukemia Research
Principal Investigator: Xiaoyan Jiang, MD, Ph.D.
Telephone: 604-675-8141
Fax:
604-877-0712
E-mail:
[email protected]
Research interest
-Molecular and cellular mechanisms of oncogenes and tumor suppressor genes in the
development of leukemia
-Gene regulation
-Leukemic stem cell biology
-Proteomics
Dr. Jiang’s research interests are focused on elucidating the molecular pathway
perturbations that cause and sustain human leukemia. The ultimate objective is to
identify new, rationally designed, molecularly targeted therapies that will be more
effective and less toxic than those presently available. Currently, she is pursuing this
interest through two lines of investigation. One is a more basic investigation of the
molecular mechanisms by which AHI-1, a novel oncogene and signaling molecule, may
contribute to the pathogenesis of a number of human leukemias and lymphomas. By
Updated: December 3, 2012
analyzing perturbations in primary human cells and in overexpression and knockdown
models, her research group has recently identified a novel AHI-1-BCR-ABL-JAK2
interaction complex that modulates BCR-ABL transforming activity and tyrosine kinase
inhibitor response of chronic myeloid leukemia (CML) stem/progenitor cells.
Understanding the functions of this interaction complex could lead to the development of
new molecularly targeted therapies.
The second line of investigation is a translational research effort in human CML where
the goals are to develop new predictive tests for identifying CML patients who are
unlikely to respond to BCR-ABL-targeted therapies, and so may be considered
immediately for more aggressive therapies, and to identify new agents or combinations of
agents that can effectively eradicate CML stem/progenitor cells.
Molecular Analysis of Hemopoiesis
Principal Investigator: Dr. R. Keith Humphries B.Sc. (Hons, Physics, University of Alberta,
1970), M.Sc. (Biophysics, University of Toronto, 1972), M.D. (University of British Columbia,
1975), Ph.D. (Medical Genetics, University of British Columbia, 1980)
Telephone: 604-675-8140
Fax:
604-877-8140
E-mail:
[email protected]
My research concentrates on the characterization of genes that underly the self-renewal and
differentiation capacity of normal versus leukemic hematopoietic stem cells. Most recently, we
have focused on the Hox homeobox family of transcription factors as candidate intrinsic
regulators of normal primitive hematopoietic cells and participants in leukemic transformation.
Expression profiling has documented differential expression of Hox genes in primitive
hematopoietic subpopulations and retroviral gene transfer has been used to engineer the
overexpression of Hox genes and leukemia associated Hox fusion genes (eg. NUP98-HOXD13)
with marked effects on hematopoiesis in mouse transplantation and embryonic stem cell models.
Among the striking functions of these wild type and variant Hox genes are their potent ability to
enhance hematopoietic stem cell self-renewal. For example we have recently shown that a fusion
of NUP98 and the homeodomain only portion of HOXA10 can trigger over 10,000-fold
expansions of HSC in 10-14 days of in-vitro culture. We have also identified the Hox co-factor,
Meis1 as an extremely potent collaborating gene with Hox and NUP98-Hox fusions in triggering
leukemic transformation. Our studies are now directed at harnessing Hox transcription factors to
achieve controlled safe ex-vivo expansion of HSC that may be useful for stem-cell based
therapies. We are also employing a number of methods to gain insight into the molecular
mechanisms and pathways underlying Hox and co-factor involvement stem cell function. These
studies include efforts to identify the cellular origin of Leukemic stem cells, direct gene targets,
protein partners and cooperating pathways. Major technologies used in the lab include FACSbased cell purification; retro and lentiviral gene transfer; ES cell gene targeting and ES in-vitro
differentiation; expression profiling; microRNA analysis; genome wide transcription factor
binding profiling; and mouse hematopoietic assays.
Updated: December 3, 2012
Stem Cells, Genetic Instability and Aging
Principal Investigator: Dr. Peter M. Lansdorp M.D. (Rotterdam, The Netherlands, 1976),
Ph.D. (Amsterdam, The Netherlands, 1985)
Telephone: 877-6070, extension 3026
Fax:
E-mail:
877-0712
[email protected]
The research focus in the Lansdorp Lab is on 1) the role of chromatin differences between sister
chromatids in cell proliferation and development 2) the role of chromosome ends (telomeres) in
the biology of normal and malignant cells and 3) the role of guanine-rich DNA in cell biology
and genome instability.
The Lansdorp laboratory described that the function of purified “candidate” stem cells is
developmentally controlled and that purified primitive hematopoietic cells divide
asymmetrically. Subsequently his laboratory found that the length of telomere repeats in
hematopoietic cells decreases with proliferation in vitro and with age in vivo. This led to the
development of quantitative fluorescence in situ hybridization (Q-FISH) techniques (using
directly labeled peptide nucleic acid probes) to measure the length of telomere repeats in
chromosomes and cells. The role of telomeres and telomerase in human (patho-) physiology is a
main research focus in the Lansdorp laboratory. Based on his work in telomere biology, Dr.
Lansdorp became interested in genetic factors that regulate telomere length. This work led to
studies in C.elegans and the surprising finding that worms lacking the dog-1 helicase gene show
deletions throughout their genome that invariably start at poly-guanine tracts. Based on this work
his laboratory cloned the Regulator of telomere Length (Rtel) gene in the mouse. The precise role
of guanine-rich DNA and RTEL at telomeres continues to be a major research focus. The other
current interest in the Lansdorp laboratory is related the possibility that (stem) cell fate is
regulated in part by chromatin differences between sister chromatids as predicted by the “silent
sister” hypothesis. For such studies the Lansdorp lab has developed novel methods to identify
sister chromatids and follow their mitotic segregation in vitro and in vivo.
UROLOGY DIVISION
Steroid Receptors
Principle Investigator: Dr. Xuesen Dong, Ph.D.
Assistant Professor of Urology, Faculty of Medicine, University of British Columbia
Jack Bell Research Centre
2660 Oak St., Vancouver, BC, Canada V6H 3Z6
Prostate Research Facility: 604-875-4818
E-mail:
[email protected]
Research Interst:
Updated: December 3, 2012
The primary interest of Dr. Dong’s research is to understand how steroid receptors regulate gene
expression and apply this knowledge to prevent cancer progression. Upon binding to steroid
hormones, steroid receptors regulate gene expression through dynamic recruitments of coregulators to promote tumor growth. Dr. Dong has identified two such co-regulators (previously
identified as RNA splicing factors, called PSF and p54nrb) that function as inhibitors of
androgen and progesterone receptors. Since androgen receptor plays a key role in promoting
prostate tumor growth, Dr. Dong is currently investigating the mechanisms on how these RNA
splicing factors repress AR functions. Information obtained from these studies would help
develop strategies that target on androgen receptor to prevent prostate cancer from progression to
the hormone-refractory/castration-resistant state.
Molecular Mechanisms of Prostate Cancer Progression
Principle Investigator: Michael E. Cox, Ph.D.
Senior Scientist, The Prostate Centre at Vancouver General Hospital
Assistant Professor of Surgery, Faculty of Medicine, University of British Columbia
Jack Bell Research Centre
2660 Oak St., Vancouver, BC, Canada V6H 3Z6
Office:
604 875-4818 or 875-4111 ext. 68369
Fax:
604 875-5654
E-mail:
[email protected]
Research Interest
Prostate cancer (PCa) is the most frequently diagnosed malignancy and the third leading cause of
cancer-related deaths in men. With support from Canadian Cancer Society and the Terry Fox
Foundation, we are also examining how prostate tumors adapt to respond to growth factors
during development of castration-resistant PCa (CRPC). Activation of insulin-like growth factor
(IGF) signaling and subsequent activation of downstream kinase signaling is implicated as key
adaptive responses that facilitate CRPC progression. We are testing the hypothesis that by
comparing gain- and loss-of-function models with adaptive changes observed in post-treated
human PCa specimens, we will elucidate functionally relevant activated components of IGF-1
signaling that can, in turn, be targeted to delay AI progression. We are assessing the use of small
molecule, antibody and antisense therapeutic modalities targeting the IGF axis to assess how
these agents alone or in combination with conventional chemotherapeutic agents impact growth
and survival signaling in androgen-dependent and CRPC model. The overall objective is to
identify and analyze prognostically relevant targets for IGF axis disruption and to determine how
targeting these key growth and survival signaling cascades can be used to optimize combinatorial
regimens for CRPC.
While the cause of prostate cancer is unknown, recurring translocation of the promoter of the
androgen-responsive gene, TMPRSS2, in frame with members of the Ets family of transcription
factors; primarily ETV1 and ERG, have been found to frequently occur in PCa patients.
Furthermore, these translocations are suggested to predict poorer prognosis especially when in
conjunction with amplification of the translocated locus or mutations of the tumor suppressor,
PTEN. However, how ETV1 and ERG expression impact disease initiation and/or progression
Updated: December 3, 2012
remain undefined. We have developed a panel of lineage-matched non-transformed and ERG
transformed prostatic epithelial cell lines. With Cancer Research Society, Inc. and CIHR
support, we are testing the hypothesis that aberrant ERG expression consistently reprograms gene
expression patterns in prostatic epithelial cells causing them to grow faster and independent of
substrate binding, and enhances their metastatic potential of prostate epithelial cells. We are
assessing how ERG induces epithelial-to-mesenchymal transition, regulate invasive behavior and
impacts androgen receptor signaling and identifying common chronic adaptive gene expression
changes in prostatic epithelial cells transformed by ERG. These studies will set the benchmark
for understanding how ERG causes prostate cancer and identify diagnostic and therapeutic
targets for treating patients with these translocations.
Selected References:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Gleave M, Cox M, Wang Y. Z., Cell biology of prostate cancer and molecular targets. In Drug Management of
Prostate Cancer. (Figg, William D.; Chau, Cindy H.; Small, Eric J. Eds.) Humana Press, (In Press).
Furukawa J, Freier SM, Peralta E, Wraight CJ, Monia BP, Gleave ME, and Cox ME. Antisense
oligonucleotide targeting of insulin-like growth factor-1 receptor (IGF-1R) in prostate cancer. The Prostate.
Accepted (PROS-09-214.R1) Aug 2009.
Cox ME, Gleave ME, Zakikhani M, Bell RH, Piura E, Vickers E, Cunningham M, Larsson O, Fazli L, Pollak
M. Insulin receptor expression by human prostate cancers. The Prostate 2009. 69:33.
Attard G, Swennenhuis JF, Olmos D, Reid AHM, Vickers E, A’Hern R, Levink R, Coumans F, Moreira J,
Riisnaes R, Oomen NB, Hawche G, Jameson C, Thompson E, Sipkema R, Carden CP, Parker C, Dearnaley D,
Kaye SB, Cooper CS, Molina A, Cox ME, Terstappen LWMM, de Bono JS. Characterization of ERG, AR and
PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer
Research 2009. 69:2912.
Palmer J, Venkateswaren V, Fleshner, NE, Klotz LH and Cox ME. The impact of diet and micronutrient
supplements on the expression of neuroendocrine markers in murine Lady transgenic prostate. The Prostate
2008. 68:345.
FitzGerald LM, Agalliu I, Johnson K, Miller MA, Kwon EM, Hurtado-Coll A, Fazli L, Rajput AB, Gleave
ME, Cox ME, Ostrander EA, Stanford JL, Huntsman DG. Association of TMPRSS2-ERG gene fusion with
clinical characteristics and outcomes: results from a population-based study of prostate cancer. BMC Cancer
Aug 11 2008. 8:230.
Deeble PD, Cox ME, Frierson, Jr. HF, Sikes RA, Palmer, JB, Davidson RJ, Amorino GP, and Parsons SJ.
cAMP-dependent protein kinase (PKA) mediated NE differentiation enhances androgen-independent growth
and tumor-forming capacity of prostate carcinoma cells. Cancer Res. 2007. 15:3663.
Ivanov N, Cowell SP, Rennie PS, Guns ES, Cox ME. Lycopene differentially blocks cell cycle progression
and induces apoptosis in PTEN-null prostate cancer cells. Clinical Nutrition. 2007. 26:252.
Rajput AB, Miller, MA, De Luca A, Boyd N, Leung S, Hurtado-Coll A, Fazli L, Jones EC, Palmer JB, Gleave
ME, Cox ME, Huntsman DG. Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to
poorly differentiated prostate cancers. J. Clin. Path. 2007. 60:1238.
Figueiredo KA, Mui AL, Nelson CC, Cox ME. Relaxin stimulates leukocyte adhesion and migration through a
relaxin receptor LGR7-dependant mechanism. J. Biol. Chem. 2006. 281: 3030.
Krueckl SL, Sikes RA, Edlund NM, Bell R, Hurtado-Coll A, Fazli L, Gleave ME, and Cox ME. Regulation of
Insulin-like Growth Factor I-mediated survival signaling in a lineage-derived LNCaP androgen independent
progression model. Cancer Res. 2004. 64:8620.
Kidney Transplantation
Principal Investigator: Dr. Caigan Du, B.Sc. (Jiangxi University, China, 1984), M.Phil
(University of Wales, Swansea, UK, 1990), Ph.D. (University of Wales, Swansea, UK, 1995)
Telephone: 875-4111 ext 63793
Updated: December 3, 2012
E-mail: [email protected]
The focus in the lab is on revealing the cellular and molecular mechanisms of
ischemia/hypothermia-induced kidney donor tissue injury prior to transplantation, and the role of
donor-derived factors in generating kidney transplant inflammation and tissue remodeling after
transplantation. We are also interested in development of new drug therapy for enhancing
survival of kidney and other organ transplants and suppressing tumor development.
PEDIATRICS, GASTROENTEROLOGY
Macrophage phenotype and function and inflammatory bowel disease (IBD) Principal
Investigator: Dr. Laura Sly, Ph.D. (University of Alberta 1998)
Telephone:
Fax:
E-mail:
604-875-3654
604-875-3597
[email protected]
The following projects are the main focus of this laboratory:

The role of the PI3kinase pathway and SHIP in IL-4-induced macrophage skewing

The role of the TGIF in macrophage phenotype and function in inflammatory bowel disease

Amending macrophage phenotype in IBD

L-arginine metabolism in fibrosis in IBD
Updated: December 3, 2012
Childhood cancer research group
Principle Investigator: Dr. CA Maxwell
Contact:
Chris Maxwell, Child & Family Research Institute
Phone:
875-2000 x4691
E-mail:
[email protected]
Interactions between various microtubule-associated proteins promote the nucleation of
microtubules for the assembly of the mitotic spindle, permitting the alignment of genetic material
and its equivalent segregation to daughter cells. Our past research has identified proteins that
work together during cell division and shown that these proteins are also vital for differentiation.
Our ongoing projects include:
1.
During mitotic spindle assembly and exit, microtubule organization and genome stability
are determined by genetic and molecular interactions between gene/proteins. Using
established technologies and phosphorylation mutants among other reagents, the interplay
between these gene/proteins will be investigated to better understand division and the
generation of genomic instability.
2.
Epithelial specialization, terminal differentiation and apicobasal polarity are reliant, in
part, upon cytoskeletal reorganization and turnover of microtubule nucleating factors.
These results provide a new perspective on differentiation and cancer risk associated with
BRCA1 mutation. Using established technologies and reagents, we will investigate
microtubule reorganization during differentiation and interrogate the mechanism(s) of
tumorigenesis for mammary tumors.
3.
Many classical cancer therapies, as well as radiation, target cell division and/or
microtubules. We will focus on testing, modifying and optimizing the effectiveness of a
novel, promising cancer therapy that disrupts microtubule organization. By genetic and/or
chemical alteration of partner proteins, we hope to broaden the clinical options to treat
aggressive adult and childhood tumors.
Signal Transduction by Protein Tyrosine Phosphatases
Principal Investigator: Dr. Catherine Pallen, Ph.D.
Childhood Cancer and Blood Research Program, Child & Family Research Institute
Tel: 604-875-2439
Email: [email protected]
Research in my laboratory investigates the cellular and physiological functions of protein
tyrosine phosphatases (PTPs). In particular, we are studying the molecular mechanisms of action
of receptor-type PTP alpha (PTP ) in signaling pathways and processes that are perturbed in
human diseases and disorders. These include pathways that regulate normal cell migration and
pediatric cancer cell migration, invasion, and metastasis; pathways that regulate mast cell
Updated: December 3, 2012
activation and are implicated in allergic diseases such as asthma; and pathways that regulate
oligodendrocyte differentiation and are implicated in myelination-related diseases such as
multiple sclerosis. Our studies employ PTP knockout mice in models of disease, and cells
derived from these mice in a variety of molecular and cellular assays.
ORTHOPEDICS
Centre for Hip Health and Mobility
Physical Activity and Bone Health Research Group
Principal Investigators: Dr. Heather McKay and Dr. Heather Macdonald
Phone:
Dr. Heather McKay: 604-875-5346
Dr. Heather Macdonald: 604-875-4111- ext. 21784
E-mail: [email protected] or [email protected]
The Centre's first major commitment is to enhance the prevention, detection and treatment of
bone and joint problems affecting the hip. Research carried out at the Centre covers the lifespan,
from primary prevention programs for children to early detection of disease in adults,
intervention programs for the at-risk elderly and improved surgical treatments.
We aim to prevent falls and hip fractures through early intervention with programs for youths and
seniors, educate and train highly skilled scientists and clinicians, detect osteoarthritis at an early
stage, treat bone and joint problems with more effective surgical solutions, including minimally
invasive surgeries, evaluate the impact, effectiveness and costs of novel interventions, translate
research that is relevant, effective and sustainable into programs, practices and policies through
knowledge integration.
More specifically Dr. McKay's Physical Activity and Bone Health Research Group targets the
relationship between physical activity and bone health across the lifespan including children and
older populations who are at high risk for osteoporosis, falls and fracture. The research projects
contain a methodological component and utilize state of the art modalities such as dual energy Xray absorptiometry (DXA), peripheral QCT (pQCT), magnetic resonance imaging (MRI) and the
new technology of high-resolution peripheral QCT (HR-pQCT)to assess bone health and the
bone response to exercise.
Falls Prevention Clinic
Principal Investigator: Dr. Teresa Liu-Ambrose, PT (University of British Columbia, 1994), M.Sc.
(UBC, 1998), Ph.D. (UBC, 2004), PDF (UBC, 2006)
Assistant Professor, Department of Physical Therapy, University of British Columbia
Updated: December 3, 2012
Telephone:
Fax:
Email:
Website:
604-875-4111 loc.69059
604-875-4762
[email protected]
www.fallsclinic.com
The Vancouver Falls Prevention Clinic is a partnership among family doctors, specialists and
health professionals with the goal of, reducing fractures, preventing falls, and, ultimately,
improving patient quality of life. The clinic was established in 2004 by the Centre for Hip Health
and Mobility in collaboration with the University of British Columbia, and the Vancouver
Coastal Health Research Institute. Falls are the leading cause of injury-related deaths in seniors,
and 30% of individuals aged 65 years and over will experience at least one fall each year.
Although falls constitute a well-recognized public health concern, there is a need for additional
research into the effectiveness of different interventions to cost effectively reduce falls in frail
senior populations.
Additional to providing a unique and valuable clinical service, the Falls Prevention Clinic
provides opportunities to various research groups who are investigating falls in seniors. The
Action Seniors! study is investigating the effects of a home activity program on quality of
life, muscular strength, balance, cognitive and daily function, and number of falls in men
and women over the age of 70 years. Most studies have shown that falls are reduced with
physical activity programs that include strength and balance training. However, it is
unknown whether persons who have had a fall that caused them to be injured can benefit
from this type of physical activity, and whether these programs are cost effective for our
health care system.
During clinical visits, patients undergo a thorough Falls Risk assessment using innovative
measures such as the Physiological Profile Assessment (PPA). This evidence-based tool, which
incorporates various tests and activities designed to assess strength, balance, vision,
proprioception and reaction time, is reliable at predicting future falls with up to 75% accuracy.
Further, a variety of questionnaires and clinical screens are administered to assess patients’
state of independent living, cognitive health and quality of life. Immediately afterwards,
patients receive a comprehensive geriatric assessment. In the literature such an assessment is
consistently found to reduce future falls by up to 60%.