Mapping the future of health care
Manitobans are on the leading edge of health research
|Dr. Lorrie Kirshenbaum looks on as a computer screen displays an image of a heart cell.
BY JOEL SCHLESINGER
Winnipeg Health Region
Wave, November / December 2012
When Dr. Lorrie Kirshenbaum decided to investigate how
genes affect the life and death of heart cells, he came up with
a novel approach to study the problem.
First, he developed a virus. Nothing too
serious - just a run-of-the-mill cold virus.
Then he took the gene in question and
inserted it into the virus. Once that was
done, he dropped the gene-carrying bug into
the heart tissue of a lab rat.
Through this process, which Kirshenbaum
pioneered in 1993, he was able to observe
how genes affect heart cells. In fact, this
technology allowed Kirshenbaum to be
among the first investigators to manipulate
adult heart cells with certain genes that
promoted DNA synthesis and cell growth.
He has also used this approach to genetically
engineer heart cells with special genes that
make them resistant to injury and death
after heart attack. In effect, he created a new
theatre in which to study heart disease and,
perhaps, how to cure it.
Now, nearly 20 years later, the gene-in-a-virus technique is helping Kirshenbaum
take another major step towards his ultimate
goal. Earlier this year, he announced that he
had identified a series of genes that switch on
when the heart muscle is deprived of oxygen.
The discovery is an intriguing one.
Learning how to prevent the genes from
switching on when starved of oxygen could
lead to new treatments to prevent damage
to heart muscle cells during heart attacks,
says Kirshenbaum, who is the University
of Manitoba's Canada Research Chair in
Molecular Cardiology at St-Boniface Hospital
Research. It could also open the door for new
approaches to treating cancer.
"What we discovered was that the genetic
pathway that gets switched on in the heart
when the cells are deprived of oxygen is the
same as the one that gets switched off in
cancer cells," says Kirshenbaum, who is also
a professor in the Departments of Physiology
and Pharmacology and Therapeutics at the
University of Manitoba's Faculty of Medicine.
"So this research could have a major impact in
the treatment for both diseases."
Kirshenbaum's ongoing investigation
into the life and death of cells is considered
world-class, and is just one example of
the leading edge research taking place in
Manitoba today. Everywhere you look,
researchers working in the lab or out in the
community are pushing the boundaries of
knowledge in their respective disciplines as
they map a path for the future of health care.
In doing so, today's researchers are building
on the legacies of a previous generation
of Manitoba research icons, people like
Drs. Bruce Chown and John Bowman,
who developed a cure for Rh disease, and
Dr. Joseph Doupe, who is credited with
transforming the University of Manitoba's
medical school following the Second World
War by emphasizing the importance of
research in the delivery of care.
But while the quest for knowledge may be as
old as the test tube itself, there are important
differences in the way researchers go about
their work today, says Dr. Peter Nickerson,
Associate Dean (Research) for the University
of Manitoba's Faculty of Medicine.
For example, researchers now have access
to an array of technologically advanced
tools to help them explore whole new
frontiers of medicine, including molecular
biology, proteomics and stem cell research.
"Compared to the tools that we had then,
the tools we have now are unbelievably
more sophisticated," says Nickerson, who
is also a member of the Manitoba Health
Research Council's Board of Directors.
He cites the case of American researcher
Craig Venter who decided about 10 years
ago to map the human genome. "That
whole exercise took about a year," he says.
Now, with the acquisition of the latest
technology in the form of the AB 5500 XL
gene sequencer, "We can do that in a week.
It's an explosion of capacity and speed that
is generating genetic data in a way we never
could do before."
Another example is the QStar Elite mass
spectrometer, used by scientists to analyze
the makeup of proteins. The instrument is
based on a design developed by a group led
by Dr. Ken Standing, professor emeritus,
and Dr. Werner Ens, professor, in the
Departments of Physics and Astronomy at
the University of Manitoba. "The earlier
versions of the mass spectrometer would take
days and give us a low level of resolution (of
a protein). Now that we have much more
sophisticated machines, they are able to go
through the analysis much faster and with a
much higher level of sensitivity. We're able
to detect low-level proteins that, before, we
didn't even know were there."
Nickerson likens advances in research
techniques to exploration of space. "It's like
looking at the moon through binoculars 50
years ago, and now you have the Hubble
telescope," he says. As a result, scientists
are better able to piece together how cells,
proteins and genes interact with each other
in the human body. "And it is through
that interaction that we are able to actually
think about how we might modify that
interaction… so that in the case of cancer,
you shut off cancer growth, or in the case
of auto-immune disease, you shut off the
auto-immune process, and have healing and
recovery of normal function. In that sense,
it is a new world," says Nickerson.
Kirshenbaum's work is a case in point.
In order to carry out his research, he
first needed to develop the technology or
technique of dropping the gene into a virus.
Then, using a number of highly sophisticated
molecular biology techniques coupled with
a laser scanning fluorescence microscope,
he was able to see where the genes he
introduced into the heart cells were located
and their effects on cell growth.
Kirshenbaum and his team of 10
researchers, comprised of students, post-doctoral
trainees, and research associates,
are not the only ones coming up with new
answers to old problems. Within the last
few years, the University of Manitoba's
Faculty of Medicine has opened, directly or
in partnership with other groups, a number
of labs to explore new fields of medical
research. They include:
The Regenerative Medicine Program
Headed by Dr. Geoff Hicks, this lab
includes eight principal investigators, 36
graduate students, 20 technologists and
10 post-doctoral fellows. The objective
is to develop stem cell therapies to treat
conditions ranging from cancer to spinal
The Manitoba Centre for Proteomics
and Systems Biology
Led by Dr. John
Wilkins, this lab has seven principal
investigators and about 35 support staff.
It was created to study proteins, the
biochemical compounds that essentially
build every living cell. Understand how
proteins operate and you can gain new
insights into what happens when cells
become infected or diseased.
These groups represent a new wave of
research that is emerging in Manitoba, all of
it aimed at developing better care for people
in Manitoba and beyond.
One of the province's more established
research groups can be found at the
Manitoba Institute for Child Health.
As the Director of Research, Dr. Terry
Klassen heads one of the largest research
organizations of its kind with more than
200 affiliated principal investigators. He
says the impact of research on patients
can be seen every day. "When you look at
our major themes of Biology of Breathing
and the Diabetes groups, what you'll
find is leading researchers and clinicians
tackling major health problems that have a
tangible benefit to care here in Manitoba,"
says Klassen, who is also Associate Dean
(Academic) and professor of Pediatrics
and Child Health at the University of
Manitoba's Faculty of Medicine. "Asthma
and diabetes are both huge issues in
Manitoba, and we've been able to bring
together the basic bio-medical researchers
and clinicians caring for these children."
In health research parlance, the idea
of gathering researchers from different
backgrounds under one roof is known as
"clustering." For example, the Biology of
Breathing group at MICH includes experts
from completely different backgrounds who
are all working on different problems. But
working side by side has its benefits. Simply
put, they feed off each other's passion,
experiences and wealth of expertise.
As evidence of this, Klassen cites the work
of Dr. Richard Keijzer, who came to work
at MICH from the Netherlands because
it offered him the opportunity to run a
research lab and still see patients.
As a pediatric surgeon, Keijzer performs
minimally invasive laparoscopic procedures
on newborn babies. But he also conducts
important research on lung development
problems of the fetus in utero. His
experimental techniques will someday
lead to a less invasive treatment for what's
referred to as a "diaphragmatic hernia," a
developmental defect in utero that causes the
lungs of newborns to be malformed, leading
to lifelong breathing problems.
Keijzer's innovative research involves
nano-technology. Together with Dr.
Malcolm Xing, he developed a treatment for
the disorder using nanoparticles - which are
essentially engineered molecules - that has
already shown promise in the lab. A cure is
likely still a number of years away, but in the
meantime, Keijzer carries on as a pediatric
surgeon, helping to improve outcomes for
mothers and newborns. "He (Keijzer) is a
clinician who brings a very important skill
to the province," explains Klassen. "By
recruiting him, with a strong commitment to
research, the kids in Manitoba now benefit."
Working alongside Keijzer, who was
recently named the U of M's Thorlakson
Chair of Surgical Research, are Xing, an
assistant professor in the Department of
Mechanical and Manufacturing Engineering
at the University of Manitoba's Faculty of
Engineering, and an expert in bio-engineering
and nano-medicine, and Dr. Andrew
Halayko, Canada Research Chair in Airway
Cell and Molecular Biology at the University
of Manitoba, Head of the Biology of Breathing
Group, and a leader in personalized medicine
and lung disease.
While they're all focused on their own
specific research, their work frequently
intersects. For example, if Halayko is
trying to figure out how to regenerate lung
tissue, he may seek out the experience
of Keijzer, who treats pediatric patients
with lung disorders. Or Xing may develop
a new form of fibre that can serve as a
framework to create living airway tissue in
a lab that Keijzer and Halayko can use in
their research. "That's the very essence of
clustering," says Klassen.
The Manitoba Health Research Council,
which already plays an important role in
helping to fund new research in Manitoba,
sees merit in supporting the clustering
concept. As Nickerson explains, efforts
are underway to develop core strengths
throughout the research community that
can be bolstered through additional funding
and recruitment. "For us to be successful, for
us to compete for federal funding, for grant
funding, and investment by industry, we
have to be focused. And focus means getting
groups of people to cluster together and say,
'We're going to work on a challenge; this is
going to be our focus.'"
In addition to the Biology of Breathing
group, Nickerson says there are many other
examples of clustering going on in Winnipeg's
research community. The Cardiac Sciences
group at St-Boniface Research, which includes
Kirshenbaum, is one example. The HIV
research group at the National Microbiology
Laboratory, which includes Drs. Frank
Plummer and Keith Fowke, is another. "We
clearly have strengths, areas where we have
well-established groups leading in their
area and who are successful at getting grant
funding," says Nickerson.
The concept of clustering can also be used
to link researchers in different organizations.
Take, for example, a project touted by
the MHRC that involves people from the
University of Winnipeg, Health Sciences
Centre and the Winnipeg Health Region.
As Dr. James Currie, Dean of Science
at the University of Winnipeg, explains,
scientists in the university's Physics
Department are working with staff from
HSC and the Region on a new method of
producing medical isotopes that doesn't
require a nuclear reactor.
"We are creating medical isotopes using
a linear accelerator," Currie says. Someday,
their work may lead to a replacement for the
isotopes produced at Chalk River, the aging
nuclear reactor in Ontario. This new method
will produce little waste - unlike a nuclear
reactor. Currie calls it a "green way" of
producing the isotopes necessary for medical
imaging used in mapping cancerous tumours
and other disease. Demand for isotopes is
high all over the world, so it's likely that
innovation here in Winnipeg will benefit
health care everywhere.
The U of W is also home to several
other MHRC-supported researchers,
including those working in the field of
environmental science. "Dr. Charles Wong is
a Canada Research Chair in Environmental
Toxicology," Currie says, adding that
Wong has recently received an MHRC
establishment grant. He is studying the
persistence and fate of man-made chemicals
on the environment - a subject obviously
critical to human health." Normally, when
people think of the MHRC, they might think
of medical school," Currie says. "But here's
a chemist who is also in the Department of
Environmental Studies and Sciences."
The idea of clustering is not limited to
the hard sciences. As Nickerson points out,
community health research has become an
increasingly important component of health
research overall. "There are researchers who
are looking at how social environments affect
health," he says. "How do they put people
at risk for disease? If you can prevent those
situations, then you can prevent diseases
from occurring in the first place."
He points to the example of the Diabetes
Research Envisioned and Accomplished
in Manitoba (DREAM). This group of
researchers, scientists and medical doctors is
working with community outreach workers
and others to tackle the growing problem of
Type 2 diabetes among young people, mostly
in northeastern Manitoba. In addition to the
lab work that will help identify biomarkers
that may signal the early warning signs of
Type 2 diabetes, other members of the team
are looking at how other factors, such as
physical activity, sleep, diet and stress may
affect a child's health. "Why is health care
so expensive? Because we are reacting all the
time to the diseases we are presented with as
opposed to investing in prevention. Those
investigations are looking at how to help
people avoid (developing disease) in the first
place," says Nickerson.
Beyond Winnipeg, MHRC is also
supporting health-care research focused on
rural areas. "Historically, most of the funding
that has been provided by MHRC is for
researchers based in Winnipeg, primarily
for the University of Manitoba," says Dr.
Dean Care, acting Vice-President, Academic
Provost at Brandon University. But in
the last few years, researchers at Brandon
University's Faculty of Health Studies have
received MHRC funding, which is then used
to leverage more funding from the national
fund providers, such as the Canadian
Institutes for Health Research.
Care is a member of the research team
that has received funding from MHRC. The
team is studying the health of rural post-secondary
students at Brandon University
and the University of Saskatchewan campus
in Prince Albert. The goal is to identify ways
to help students avoid developing unhealthy
behaviours. Like the saying goes, an ounce of
prevention is worth a pound of cure.
The student health study is just the
beginning. "The 'M' in MHRC stands
for Manitoba, but it has been seen as the
Winnipeg Health Research Council," Care
says. "Today, this funding support means
there is more than just lip service being paid
to rural areas, and we see ourselves as part of
the future of health-care research. That's very
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Read the November / December 2012 issue of Wave