Emerging Fields and Break­through Discoveries

Breathing easier through epigenetic research

Denise Daley
Denise Daley

Can the environment affect our genes? According to a trio of researchers at UBC it can, and it does. Their respective studies in respiratory disease epigenetics have helped make the university a leader in this emerging field, which considers the relationship between our environment and our genes. How we live can, in fact, alter our gene expression in a way that may affect the development of cancer, asthma or neurodegenerative diseases.

Dr. Michael Kobor, a professor at the Centre for Molecular Medicine and Therapeutics, and the Canada Research Chair in Social Epigenetics, wants to understand how the environment affects the packaging process of DNA (each of our tiny cells contains a DNA strand long enough to stretch more than two metres). To that end, his lab is working with faculties across campus and colleagues around the world to determine how the environment – including socio-economic status – plays a role in gene expression and affects conditions such as fetal alcohol syndrome, asthma and chronic obstructive pulmonary disease.

Other asthma-related epigenetics research includes Dr. Denise Daley’s investigation of whether parents’ smoking habits trigger genetic changes in their offspring.

Daley, Canada Research Chair in Genetic Epidemiology of Common Complex Diseases, and her team are looking for a type of genetic alteration known as “methylation” – that is, when a carbon and hydrogen compound latches onto part of the DNA and modifies how that cell develops and functions. Their goal is twofold: to prove methylation triggers a cascade of consequences that lead to childhood asthma and/or allergies, and to determine when those changes are triggered.

Then there is research that builds on a previous study, which demonstrated that breathing in diluted and aged diesel exhaust may affect about 400 genes and lead to fundamental health-related changes in the body.

Chris Carlsten (Photo - Don Erhadt)
Chris Carlsten (Photo: Don Erhardt)

Dr. Chris Carlsten of UBC’s division of Respiratory Medicine, and chair in Occupational and Environmental Lung Disease, led the inquiry. Volunteers were placed in a polycarbonate-enclosed booth about the size of a standard bathroom and made to breathe in air-pollutant fumes that were equivalent to driving along a highway in Beijing, or working in a busy port or industrial site on a hot and windless day.

Now Carlsten’s team is taking the next step and studying how these changes may be translated to health issues, even when there are no obvious symptoms.

“Usually when we look at the effects of air pollution, we measure things that are clinically obvious – air flow, blood pressure, heart rhythm,” says Carlsten. “But asthma, higher blood pressure or arrhythmia might relate to the gradual accumulation of epigenetic changes. So we’ve revealed a window into how these long-term problems may arise. We’re looking at changes ‘deep under the hood.’”

And that just might allow us all to breathe easier.

From personalized prescriptions to DNA in space

Corey Nislow and his team have developed strains of yeast that are heading to the International Space Station. (Photo: Paul Joseph)
Corey Nislow and his team have developed strains of yeast that are heading to the International Space Station. (Photo: Paul Joseph)

Innovative. Paradigm-shifting. Out-of-this-world – literally. All different ways you can describe the research of Dr. Corey Nislow in pharmacogenomics – research that is poised to launch us into the future.

Pharmacogenomics is a burgeoning field that combines pharmacology with genomics to generate exciting new applications. Nislow, an associate professor in the Faculty of Pharmaceutical Sciences, is collaborating with Genome BC and the BC Pharmacy Association on a project – the first of its kind in North America – that has the potential to revolutionize healthcare delivery.

By using genomics to predict more accurately an individual’s response to a drug and its dosage, the project hopes to eventually usher in a new era of personalized medicine, in which pharmacists can use each person’s genetic makeup to make medication use safer and more effective.

Following the sequencing of the first human genome in 2000, scientists have known that genetic information could be used to personalize medicine. “To say it really simply, some of your genes will have variants… that will make you metabolize some drugs quicker than others, make you metabolize some drugs slower than others,” or even preclude an individual from metabolizing a drug at all, says Nislow.

Yet, he says, “there hasn’t been a healthcare profession that’s stepped up and said we’re gonna take this on.”

This is where pharmacists, working with Nislow’s team, are stepping up to the plate. Community pharmacists provide the perfect interface between patients and new prescription practices. And with major technological advances allowing genetic testing to be conducted on a large scale at a much lower cost, the ability to develop a pharmacogenomic approach has never been better.

During the pilot phase of the project, Nislow and his team have partnered with 34 pharmacists at 31 BC pharmacies to recruit patients to participate in the study and collect their saliva samples. Once the samples reach the UBC Sequencing Centre at Pharmaceutical Sciences, the researchers use next-generation sequencing (NGS) to extract genetic data that can be used to determine how an individual responds to different medications.

While the researchers are looking at all medications where genetics is known to have an impact, they are using warfarin (Coumadin) as a benchmark for this phase of the study. Warfarin is a particularly fitting drug for phase one this study, as it is a long-term treatment with an optimum dosage that varies greatly from individual to individual. There is also a dosing algorithm that uses genetics to determine the correct dosage and delivery interval of warfarin specific to each genome.

A key component of phase one has been working with pharmacists to develop robust operating procedures for sample collection, processing and sequencing. “We’re focusing on the mechanics of getting the genome from a pharmacy, bringing it to the lab and decoding it with a high enough accuracy and in a fast enough time frame that you could actually benefit from that information,” says Nislow.

If phase one successfully demonstrates the feasibility of pharmacy‑based genomic testing, phase two will see an expansion of the project into a wider base of community pharmacies, where pharmacists will begin to implement genetic information into patient drug therapy decisions. With more than 1,000 community pharmacies across the province, there is ultimately the potential for all BC residents to access the testing, regardless of where they live, and for pharmacists in BC to be at the forefront of game-changing innovation.

It’s all part of a giant leap forward in delivering medicine in a way that is streamlined and individually tailored, helping to reduce drug therapy costs, manage healthcare sustainability, and most importantly make people healthier.

Another project headed by Nislow seems to veer more towards science fiction than science: he has been sending modified yeast cells up to the International Space Station in order to research how reduced gravity affects human genes. Yeast is an ideal specimen for this type of study, as it has retained enough features in common with human cells over its evolution to still inform human cellular response.

The project has applications both beyond the final frontier and back here on earth, from understanding how reduced gravity will affect astronauts’ DNA to discovering ways to mimic DNA damage caused by cosmic radiation in cancer cells that will cause them to kill themselves.

It’s exciting stuff – to see the future happening right here at UBC, where discomforts and diseases that affect patients today are on their way to becoming a thing of the past, and how yeast in space could one day help humans land safely on Mars.

Building an environment to combat prostate cancer

Dr. Martin Gleave is a man with many hats. Not only does he head the Faculty of Medicine’s Urologic Sciences department, he is also a clinician, renowned research scientist, urologic surgeon, and founder of a UBC spin‑off company, OncoGenex Pharmaceuticals.

It’s a formidable resume. And that’s before you factor in his role as the chief architect of an environment that is bringing together leading researchers to share their expertise to combat prostate cancer, the most prevalent cancer in BC men and the second leading cause of cancer deaths.

Gleave is the executive director and a leading researcher at the Vancouver Prostate Centre (VPC), a research hub hosted by UBC and the Vancouver Coastal Health Research Institute that he co‑founded with prominent cancer researchers in 1998. It has since become one of the world’s most respected cancer research facilities. He is also CEO of the Prostate Centre’s Translational Research Initiative for Accelerated Discovery and Development (PC‑TRiADD), a national centre for excellence in research and commercialization.

Together, these programs have created a collaborative and fertile environment with a rigorous bench‑to‑bedside philosophy, focused on advancing clinical research discoveries into treatments with minimal delay. It is able to do so by combining strengths in cancer genomics with the research and development of new drugs treatments.

Researchers like Drs. Colin Collins and Yuzhuo Wang are teaming up to pave the way for personalized oncology. By sequencing the genomes of cancer tumours, Collins and Wang, who are senior scientists at the VPC, are predicting more precise and effective anti‑cancer therapies, targeting the specific molecular characteristics of the malignant growth. A breakthrough blood test developed at VPC by a team led by Dr. Kim Chi is now allowing the genetic profiling of cancers in patients that is already transforming the treatments they receive.

A recent breakthrough in drug development has revolutionary potential for treating castrate‑resistant prostate cancers. The breakthrough was made possible through a collaboration between leaders in seemingly disparate scientific domains. Dr. Paul Rennie is considered a long‑established world leader in the biology of androgen receptors, key sites on cells where overexpressed hormones bind and cause prostate cancer. Dr. Artem Cherkasov’s expertise lies in in‑silico or computer‑aided drug design, which uses bioinformatics tools to test and develop new drugs, bypassing the lengthy, expensive initial process of drug discovery using classic in‑vivo methods.

Their discovery takes a completely new approach to treating castrate‑resistant prostate cancer. As this form of cancer is driven by the androgen receptor, other drug treatments have attacked prostate cancers by trying to lower production of the male sex hormone, testosterone, or block its binding to the androgen receptor. While often initially effective, the cancer will evolve to overcome these chemical changes and become “castration‑resistant,” where it adapts to makes its own androgen, cooperate with other survival pathways to support androgen receptor activity, or eventually completely bypass the need for the androgen receptor as a driver gene. To overcome these adaptive mechanisms, Rennie and Cherkasov have designed a drug that, rather than blocking the site where the androgen binds to the androgen receptor, instead blocks the site where the androgen receptor binds to DNA – effectively taking the wheels off the car and putting the cancer “up on blocks” to prevent it developing, regardless of what is happening to the fuel. It is the apex anti‑androgen that has caused quite a stir in prostate cancer research circles and an incredible feat of collaboration between some of the most respected researchers in their fields. It is most importantly a discovery that could have life‑altering impacts on patients. In December 2015, UBC announced that the discovery had been licensed to Roche, in UBC’s largest licensing deal to date.

Advancing the world’s bio‑economy

With a childhood immersed in British Columbia’s breathtaking nature, the forest occupies a special place in Dr. James Olson’s past. Through his research, it is set to play a vital role in a more sustainable future for us all.

Olson, a professor in the Department of Mechanical Engineering, is a member of the Forest Bio‑products (FBP) Institute at UBC. The FBP Institute brings together a multi‑disciplinary research team, working collaboratively with a single goal in mind: to advance the world’s bio‑economy, an economy based on renewable biological resources.

This invaluable network couldn’t have been formed at a more critical time. As the world’s population booms and the middle class of countries such as China and India expand rapidly, our consumption of non‑renewable resources is skyrocketing – causing irreversible damage to our planet.

The FBP Institute, though, is maximizing the British Columbian advantage to lead the bio‑revolution: extracting high‑value products from biomass, an abundant material sourced primarily from residual and waste products from BC’s forest industry, to create alternative and sustainable materials, energy, and chemicals.

The FBP Institute’s “superhero team” of researchers, as dubbed by Olson, has already spurred innovation in the bio‑economy. Dr. Paul Watkinson and his team, for example, are working on developing and testing high quality synthetic gas, or “syngas,” derived from biomass, using cutting‑edge technology at the UBC Pulp and Paper Centre. This renewable source of power has the potential to replace natural gas and run our future fuel cells.

Dr. Jack Saddler and his team are working on turning forest residues and “wastes” into liquid fuels and chemicals in what is termed “biorefining.” Analogous to oil refining, in which multiple fuels and useful products are extracted from petroleum, biorefining is a much more sustainable and economic way of manufacturing these products.

Olson has long been driving innovation in the bioeconomy and beyond. Following revolutionary energy‑saving developments in pulp and paper industry technology, Olson is currently working with Dr. Mark Martinez to formulate a lightweight, low‑density cellulose material from micro and nano‑fibres – part of a new class of “bio‑materials.” The FBP Institute scientist Dr. Frank Ko is also working to develop new materials of this kind.

Bio‑materials have the potential to replace fossil‑fuel materials, and have a wide and exciting range of applications: from sound‑proofing and insulation to advanced cosmetics and high‑strength turbine blades, and even to bio‑compatible scaffolds for 3D printing of human tissue.

These are just some of the many exciting projects being initiated by The FBP Institute researchers, including programs such as a new Master of Engineering in Green Bio‑Products to train and educate the next generation of bioeconomy innovators. The BC forest is intimately woven into the fabric of our province and Olson is optimistic about its potential – a potential that The FBP Institute is harnessing to bring about a greener future. “It’s an exciting time to be part of the biorevolution,” he says, “and to be part of the forest industry.”

The research stories above, along with others, can be found on the website of UBC Research and International. To learn more about UBC research, please visit research.ubc.ca

Ancient medicine: an antidote for the post‑antibiotic era?

Julian Davies and Shekooh Behroozian inspect a bucket of clay. (Photo: Chris Balma)
Julian Davies and Shekooh Behroozian inspect a bucket of clay. (Photo: Chris Balma)

According to UBC research, naturally occurring clay from Kisameet Bay, BC – long used by the Heiltsuk First Nation for its healing potential – exhibits potent antibacterial activity against multidrug‑resistant pathogens.

The researchers recommend the rare mineral clay be studied as a clinical treatment for serious infections caused by ESKAPE strains of bacteria.

The so‑called ESKAPE pathogens – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species – cause the majority of US hospital infections and effectively “escape” the effects of antibacterial drugs.

“Infections caused by ESKAPE bacteria are essentially untreatable and contribute to increasing mortality in hospitals,” says UBC microbiologist Julian Davies, co‑author of the paper. “After 50 years of over‑using and misusing antibiotics, ancient medicinals and other natural mineral‑based agents may provide new weapons in the battle against multidrug‑resistant pathogens.”

The clay deposit is situated on Heiltsuk First Nation’s traditional territory, 400 kilometres north of Vancouver, in a shallow five‑acre granite basin. The 400‑million kilogram (400,000 tonne) deposit was formed near the end of the last Ice Age, approximately 10,000 years ago.

Local First Nations people have used the clay for centuries for its therapeutic properties – anecdotal reports cite its effectiveness for ulcerative colitis, duodenal ulcer, arthritis, neuritis, phlebitis, skin irritation, and burns.

In the in vitro testing conducted by Davies and UBC researcher Shekooh Behroozian, clay suspended in water killed 16 strains of ESKAPE bacteria samples from sources including Vancouver General Hospital, St. Paul’s Hospital, and UBC’s wastewater treatment pilot plant.

No toxic side effects have been reported in the human use of the clay, and the next stage in clinical evaluation would involve detailed clinical studies and toxicity testing. Loretta Li, with UBC’s Department of Civil Engineering, is conducting mineralogical and chemical analyses of the clay as well.

Advanced materials: smart windowpanes

Kenneth Chau holds a glass sample used in his latest research. (Photo: Matthew Grant)
Kenneth Chau holds a glass sample used in his latest research. (Photo: Matthew Grant)

Imagine if the picture window in your living room could double as a giant thermostat or big screen TV. A discovery by UBC researchers has brought us one step closer to this becoming a reality.

Researchers at UBC’s Okanagan campus found that coating small pieces of glass with extremely thin layers of metal like silver makes it possible to enhance the amount of light coming through the glass. This, coupled with the fact that metals naturally conduct electricity, may make it possible to add advanced technologies to windowpanes and other glass objects.

“Engineers are constantly trying to expand the scope of materials that they can use for display technologies, and having thin, inexpensive, see‑through components that conduct electricity will be huge,” says UBC associate professor and lead investigator Kenneth Chau. “I think one of the most important implications of this research is the potential to integrate electronic capabilities into windows and make them smart.”

The next phase of this research, adds Chau, will be to incorporate their invention onto windows with an aim to selectively filter light and heat waves depending on the season or time of day.

The theory underlying the research was developed by Chau and collaborator Loïc Markley, an assistant professor of engineering. Chau and Markley questioned what would happen if they reversed the practice of applying glass over metal – a typical method used in the creation of energy efficient window coatings.

“It’s been known for quite a while that you could put glass on metal to make metal more transparent, but people have never put metal on top of glass to make glass more transparent,” says Markley. “It’s counter‑intuitive to think that metal could be used to enhance light transmission, but we saw that this was actually possible, and our experiments are the first to prove it.”

Fuel cells are the future

Last year’s recall of 11 million Volkswagen diesel vehicles highlights the challenges of reducing emissions from fossil fuel-powered cars. Fortunately, there’s an alternative and it has zero emissions. The fuel-cell car is currently being developed by major automakers including Mercedes-Benz, Toyota and Hyundai.

Walter Mérida, director of UBC’s Clean Energy Research Centre (CERC), has been researching fuel-cell technology for more than 15 years. When Mercedes‑Benz rolls out its new fuel‑cell cars in a few years, they’ll feature Canadian technology.

What are some of the benefits of fuel cells?
Fuel cells convert hydrogen and other fuels into electricity quietly, efficiently, and without pollution. A fuel-cell car produces zero emissions. You’ll only see water coming out of the tailpipes. And it’s quickly refuelled, unlike battery‑powered cars, which can take hours to recharge.

Fuel cells can be used to build a renewable, carbon‑free energy system if you produce the hydrogen from renewable sources, such as hydroelectricity. The geopolitical impact can be profound. Countries without fossil fuel sources such as oil or natural gas can generate the energy they need, cleanly.

How far along is fuel-cell adoption?
Auto manufacturers are investing in fuel-cell cars, trucks, and other types of vehicles. Hyundai is already leasing fuel-cell SUVs in Vancouver, while Toyota expects to begin delivery of hydrogen fuel-cell cars in California next year. Mercedes-Benz is expected to introduce its new generation of fuel-cell cars in a few years.

By 2017, fuel-cell car sales are expected to approximate that of electric cars in their early adoption stage.

As well, refuelling networks are being laid out in places like California, where there are 10 public hydrogen fuel stations, and in Japan, where 23 stations have opened and hundreds more are being planned. Germany recently opened its first hydrogen filling station on the autobahn. There are plans for the rollout of more than 50 stations across Europe over the next few years.

Fuel cells are already part of the power grid in some cities. New York is an example. You could also have small applications, such as cellphones, because fuel cells can be miniaturized.

Tell us about your work on fuel cells.
My group at CERC is working on new techniques to ensure the durability and reliability of fuel cells as they move into mass manufacturing. We collaborate with hydrogen fuel-cell manufacturer Ballard Power Systems, based in Burnaby, and with Germany’s Mercedes-Benz.

British Columbia is seen around the world as the leader in this field, and so when Mercedes-Benz decided to open their own production facility for automotive fuel cells in 2012, they chose to come to BC.

Is the internal-combustion engine slated for the trash heap?
Not quite yet. Right now about 80 per cent of our primary energy supply comes from fossil fuels – coal, oil and gas – and combustion will remain an important technology for many more years.

The main barriers for fuel-cell technology at the moment are the cost of generating power from it, and the lack of an efficient, extensive refueling network. But I see a future for hydrogen fuel cells as a way out of transportation’s extreme dependence on fossil fuels.

You helped develop the new Master of Engineering Leadership (MEL) in Clean Energy at UBC. How does it fit into all this?
We’re at the threshold of a big transition in the way we think about energy. The global investment in renewable energy was more than $200 billion in the last year alone. Engineers and executives should know how clean technology can transform the global economy. The MEL offered by UBC Applied Science will give them that perspective through a combination of management education and advanced engineering courses.

Wearable electronics will change the way we live

From smart bodysuits for space explorers, to ski goggles that track your speed and calories, to sleek jewellery that charges your smartphone, wearable technology is advancing so quickly that what used to be the stuff of sci-fi is quickly becoming part of everyday life.

Flexible Electronics and Energy Lab, led by electrical engineering professor Peyman Servati is the main research centre at UBC for the development of wearable technology. According to Servati, the wearables market is exploding with growth, projected to grow from $20 billion worldwide in 2015 to $70 billion by 2025. In this Q&A, he talks about the technological challenges that must be overcome for the market to grow to its full potential.

What are wearables?
Wearables help better integrate our computers with our everyday lives. Examples of wearable devices include fitness monitors such as Fitbit and Apple Watch. Here in Canada, you’ve probably also heard of Vancouver‑based Recon Instruments’ ski goggles that provide pace, cadence and calorie readouts as you ski. There are also biometrics-tracking textiles and shirts, which use embedded sensors to measure your heart rate, sweat, and other physiological responses. Some new wearables even have built-in solar and battery films to power the embedded electronics.

So wearables get lots of love from athletes and coaches, but how can the average person use them?
The biggest potential application of wearables is in healthcare. A patient with chronic health issues could put on a shirt to track and report his vital signs such as pulse rate, blood pressure, sweat, and breathing patterns to a health care provider. This information could tell medical professionals how the patient is doing on a real-time basis.

A wearable device that detects tremors and sweating could be helpful for someone with Parkinson’s disease. Combining movement and sweat measurements can give you richer information. This is an area I’m working on with Dr. Martin McKeown, director of the Pacific Parkinson’s Research Centre at the UBC Faculty of Medicine.

What type of wearable is best for people with chronic health issues?
Many people with chronic conditions need good monitoring so that their treatment becomes more personalized and more accurate. But we don’t know yet what form it should take. More work needs to be done. It could be a wristband; it could be a shirt. But they should be comfortable, non‑irritating, and unobtrusive. They have to be able to store power efficiently, or be self-powered; that’s why my lab is looking for the best technology for solar cells that can be embedded in textiles.

Medical professionals should participate in designing these devices, and there needs to be regulatory oversight too.

What are the some of the development challenges for wearable, flexible electronics?
Accuracy and reliability of information is a big one. Even small movements can result in loss of accuracy for the data. Can you trust the data that’s coming through? How do you send the information securely to the doctor or hospital? How do you protect the wearer’s privacy?

Comfort is very important. This also applies to the power source. My lab is looking at benign materials, such as nanofibres, in collaboration with materials engineering professor Frank Ko of UBC’s Advanced Fibrous Materials Laboratory.

We’re also looking at coating methods that will be comfortable to wear. You don’t want to impose another hard, bulky gadget on people with chronic health conditions. Our research goal is to make everything smooth and flexible, like a natural part of clothing.

Developers of wearables are also working to bring down costs. This is already happening with a growing number of tech companies and manufacturers getting involved in production. In just five years we could see smart devices and textiles going for as little as $10. Future wearables could become as inexpensive as Band-Aids.

You recently co-founded UBC startup, Texavie, to develop wearables. How do you plan to compete in this space?
While it’s a bit early to give specifics, Texavie will focus on devices that can improve the sports performance of recreational athletes. This will give us the opportunity to perfect technologies that could be used for other applications, like healthcare.

Q&As courtesy of UBC Public Affairs.


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