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HUMAN KIDNEY

ORGANOIDS
EVENT HIGHLIGHTS
APRIL 2018
POTENTIAL
OSTEOPOROSIS
TREATMENT

Drs. Earl Davie, Ross MacGillivray, and Eddy Fischer.

INNATE DEFENCE
Photo credit: Kitty Liu

REGULATOR PEPTIDES
director’s note

Notes from Conway’s Chair - March 2018


“Canadian transfusion; their efforts. And you will be impressed! With
accomplishments in • Early introduction of iron chelation therapy minimal guidance, CBR trainees also coordinate
science and scholarly for patients with myelodysplastic syndrome to a Career Development program, the Blood Labs
prolong survival;
inquiry have long • The development of polymer-based heparin Outreach program, and the Graduate Award
been a source of reversal agents to prevent bleeding; program, to name but a few initiatives that
national pride. • Characterization of mechanisms underlying build multiple proficiencies that will be of value
However, by various heparin induced thrombocytopenia; beyond academia. People often ask what inspires
• Discovery of a new protein that promotes clot
measures, Canada’s me to do this job … it’s the students!
formation and atherosclerosis;
research competitiveness has eroded in recent • Implementation of personalized approaches
years when compared with international peers. to care for patients with hemophilia; Our educational programs are almost entirely
The change coincided with a period of flat-lining • Development of new techniques for pathogen supported by the philanthropic gestures of our
of federal spending … reducing available support inactivation of platelets; partners in industry. It is they who sponsor the
• Methods to isolate and culture muscle cell
for independent, investigator-led research Earl Davie Symposium, the Norman Bethune
progenitors that are important in growth and
by frontline scientists and scholars.” And so repair; Symposium, the Annual CBR Research Day,
the 2017 Executive Summary of the Naylor • Identification of innate lymphocytes that limit our Summer Studentship Program (the largest
report, “Investing in Canada’s Future,” began. cancer spread, elucidation of the effects of and most comprehensive of its kind at UBC)
It’s a sobering and necessarily highly public anti-retroviral drugs on HIV-exposed infants and the weekly seminar series. We are deeply
in African countries.
recognition that research support in Canada appreciative of their investments and their trust.
The list goes on and on (check the CBR website
has gradually and steadily been withering, These programs are not only of direct benefit
for a glimpse). Just imagine what could be
despite the “high levels of talent, expertise, and to the trainees, but they yield excellent and
accomplished if we had more resources and
dedication.” Although there are positive signs highly productive research opportunities. We
sustained funding for our creative and talented
that the government is responding to this crisis, are entering our 6th year of the Bayer-sponsored
CBR teams?! Hopefully, we will find out in the
it will take major efforts to get Canada back to its UBC Bleeding Disorders Collaboratory, a
coming years.
rightful trajectory. CBR initiative that is having a major positive
impact on hemophilia research and patient care
The CBR remains dedicated to our students and
In spite of the fiscal challenges, CBR research throughout the province. In March 2017, Shire
trainees, continuously adding and improving
teams have been weathering the storm and, sponsored a CBR-hosted national symposium on
programs that will nourish the aspirations and
indeed, flourishing in the lab and the clinic. This the management of patients with hemophilia and
career-developing needs of this next generation
is measured not only by the number and value factor VIII inhibitors. There are, in fact, many
of scientists and clinicians. The CBR Education
of prestigious grants and awards received by our other examples of industry-sponsored events at
Program is currently and ably led by Julie Kora
senior investigators and their trainees, but by the CBR. Most notable of all our partners is the
who took up the reins mid-year when Anna
the number and quality of the clinically relevant Canadian Blood Services (CBS). Our colleagues
Sinova went on maternity leave. Together, they
scientific advances that they have made. To name at the CBS continue to provide critical support
have propelled CBR’s enrichment program to
but a few, these include: for the CBR’s infrastructure, education and
• Developing novel treatments for osteoporosis help undergraduate, graduate, medical, and
training; and here in Vancouver, we have the
using derivatives of traditional Chinese postdoctoral students develop skills that will
fortune of having their scientists on site - an
medicines; hopefully be of benefit wherever they may land
• Generation of innate defense regulator incredibly enthusiastic and bright group of
career-wise. Recognizing the importance of
peptides to treat inflammatory and infectious investigators and good friends!
developing skills in communication for success
diseases;
• Applying high-resolution cryo-EM imaging in all fields, the Knowledge Translation (KT)
It is natural that senior scientists/professors
of Salmonella injection components that may Committee comprises clinical and research
should eventually hand over the baton to the next
yield novel antibiotics; trainees from throughout the CBR. They write on
• The creation of a wound dressing material to generation of younger scientists. In December
a wide range of topics, releasing a weekly news
locally enhance clotting; 2017, the CBR witnessed the retirement of Dr.
article, a monthly newsletter, and a biannual
• The discovery of safer and more effective clot Ross MacGillivray, a founding member of the
dissolving agents; magazine that is distributed at the two major
CBR and its first Director. We will miss him …
• Optimization of the storage temperature annual CBR symposia - Norman Bethune and
indeed, we already do! He set the bar high, in all
for prolonging platelet survival prior to Earl Davie. Indeed, this issue is a product of
that he did, in his research and for the CBR. The

2
CBR (and UBC) owes him a debt of
gratitude. We wish him well.
TABLE OF CONTENTS
To the future? We continue to seek
new partnerships and stronger
links between the lab and the clinic. RESEARCH EVENTS
Searching for new sources of funding
remains a priority. The establishment of
the Sheldon Naiman and Linda Vickars 6 Osteoporosis
Treatment 13 Conference
Pseudomonas
on
Endowment will provide new means

7 Iron Chelation
14 Earl Davie
of supporting initiatives in benign
hematology. In the past year, the School Therapy Symposium
of Biomedical Engineering was created
at UBC, through a strategic partnership
between the Faculties of Medicine and
Applied Science. In 2018, the CBR is
8 Human Kidney
Organoids 20 Proteolysis
Society Meeting
seizing a unique opportunity that will
help to further propel the integration
of life scientists and physicians with
bio-engineers. We are welcoming
9 Innate Defense
Regulator Peptides 22 STEMCELL
Technologies Visit
two accomplished UBC Professors
of Applied Science, Professors Karen
Cheung and Hongshen Ma, providing
10 Extending
Platelet Shelf Life 23 American
Hematology Society
them with memberships and CBR
research space in the Life Sciences
Centre. Profs Cheung and Ma are
founding members of the School of
12 Bacterial
Response
Starvation
24 Paddleboarding
Extravaganza
Biomedical Engineering, and both
have already cemented collaborative
research projects with CBR and Life AWA R D S PROFILES
Sciences Institute members. They
bring with them fresh ideas, new
technologies, opportunities for growth, 5 Biophysical
Society Fellow 18 Deb Chen
and a whole bunch of enthusiastic and
skilled students! We welcome them
and look forward to having them join
us in ensuring that the CBR continues
11 CBR Travel
Awards 27 Ross MacGillivray
to flourish as a world-class translation

17 Michael John
research centre.
Page Award OPINION
For the year gone by and the year
coming, special thanks to our CBR
Office Managers, Hana Kim and Mira
Milutinovic, who work so hard for all 26 Faculty
Award
Research
16 Pro-Vaccination
Strategies
of us.

Overall, although Canada’s research


competitiveness may have “eroded,” I PA R T N E R S H I P
21 To Transfuse or
Not?
believe that we at the CBR have much
to be proud of. Naturally, we could
always do better … And we will!
25 Bayer-UBC
Collaboratory
Ed Conway, Director
3
ABOUT CBR
The CBR aims to improve the health and well-being
of patients through innovative research in blood and
blood-related processes.

GOALS
CBR Research & Clinical Goals
• Improve the quality and safety of blood
product collection, storage and delivery
• Create new knowledge to better treat
bleeding and clotting disorders
• Develop novel approaches to
modulate the immune system to
treat inflammation and infections and
Patient-driven. Innovative. Community. promote wound repair

Over the past year, donor support has helped us develop novel approaches
to battle severe bleeding in rural areas, delineate the mechanisms of
inflammatory diseases, and increase the quality of blood products used in
transfusions – only a few examples among many pioneering discoveries.
With your continued support, the CBR will further transform innovative
ideas into life-enhancing solutions.
The CBR needs you to help fund our programs that range from $50 to
$100,000. We invite you to explore opportunities at the CBR where your
partnership with us will result in positive impacts on education, training and
meaningful research. Examples of initiatives that need your support include:

Opportunity Cost
Reward leadership in students and staff with the Neil $50
Mackenzie Mentorship Award
Expose trainees to diverse career opportunities with the
CBR Career Night
$1,000
E D U CAT I O N
Jumpstart a postdoctoral fellow’s career with the $5,000 CBR Education Commitment
Postdoctoral Transition Award • Support student research through
Support a clinical fellow in Translational Research Studies $75,000 competitive undergraduate, graduate,
and postgraduate awards
• Offer a range of stimulating educational
Make a CBR Symposium possible $25,000-
symposia, workshops, and seminars
$100,000
• Provide cutting-edge career
Explore further: CBR.ubc.ca/support-us
development opportunities for our
Edward M. Conway, MD, PhD
trainees
Director, Centre for Blood Research
Tel: 604.822.4252 | Email: ed.conway@ubc.ca

4
awards

Dr. Natalie Strynadka Chosen as


PUBLISHED BY
2018 Biophysical Society of
Canada Fellow
Knowledge Translation Committee
DESIGNER  Julie Kora
CONTRIBUTING EDITORS
Arjun Baghela
Corrie Belanger
Daniel Pletzer
Diana Canals Hernaez JULIE KORA
Ed Conway*
Enoli De Silva
Erika Siren*

D
Georgina Butler*
Houra Loghmani-khouzani* r. Natalie Strynadka is a
J. Andrew Alexander* Distinguished Professor and
Jennifer Grants
Julie Kora researcher in the Department of
Katharine Sedivy-Haley Biochemistry and Molecular Biology
Lily Takeuchi
Michael Hughes* at the University of British Columbia
Stefanie Novakowski
Usama Abbasi
and a member of the Centre for Blood
Vivienne Chan Research (CBR). She is known for
Wayne Zhao
* indicates Editorial Board member
her research in the fields of antibiotic
resistance and biophysics. Dr. Strynadka
COVER PHOTO Kitty Liu
BLOG cbr.ubc.ca recently received the honour of being
FACEBOOK /cbrubc chosen as the 2018 Fellow of the
TWITTER @CBR_UBC
INSTAGRAM @CBR_UBC Biophysical Society of Canada (BSC).
She will receive this award at the 4th
CBR magazine is published by the
Knowledge Translation Committee, Annual Biophysical Society meeting,
a group of CBR graduate students, held on May 22-25, 2018 in Vancouver,
postdoctoral fellows, research associates,
and technicians who are interested in BC.
science writing, blogging, and mixed
media communications. It is distributed
free of charge to CBR and UBC alumni, The Biophysical Society of Canada
friends, and the scientific community.
Opinions expressed in the magazine do was founded in 1985 and works to
not necessarily reflect the views of the support biophysics research in Canada
centre or the university.
Address correspondence to: through a variety of awards, programs,
The Centre for Blood Research and meetings. Annually, the BSC
4th Floor, Life Sciences Centre
2350 Health Sciences Mall recognizes researchers who have
Vancouver, BC, Canada V6T 1Z3 made extraordinary research contributions as Fellows of the Biophysical Society. To gather exceptional
The KT Committee publishes weekly
at CBR News (cbr.ubc.ca) and covers a candidates for this award, the BSC asks for nominations in the fields of biophysics and biophysical
wide range of topics: from recent research
chemistry. The selected Fellow then presents the National Lecture at the Annual meeting of the BSC.
highlights and opinion pieces on science
and academia, to event coverage and
CBR initiatives. If you are interested in
participating in the KT Committee, email
In 2010, Dr. Strynadka received a Tier 1 Canada Research Chair in Antibiotic Discovery and has
Julie at: julie.kora@ubc.ca or talk to one been recognized through numerous academic and other awards and distinctions for her outstanding
of the members! All grad students, PDFs,
RAs, and technicians are welcome to join. work. In 2012, Dr. Strynadka received the prestigious Senior International Research Scholar award from
the Howard Hughes Medical Institute. She has also been honoured as a Medical Research Council of
CONTACT Canada Scholar, a Canadian Institute of Health Research Scientist, a Michael Smith Foundation for
julie.kora@ubc.ca Health Research Senior Scholar, and was elected a Fellow of the Royal Society in 2015.
Knowledge
Translation Congratulations to Dr. Strynadka on her latest award and her many notable
Committee
Science beyond academia
achievements! C

5
research

Bromme Lab Has Found a Potential Osteoporosis


Treatment in Compound Derived from Traditional
Chinese Medicine
By CORRIE BELANGER, PhD Candidate in Hancock Lab

Figure 1. T06 binding at ectosteric site on CatK

B one deteriorating diseases such as osteoporosis affect at least 1 in


3 women and 1 in 5 men in their lifetimes, causing increased risks
of fractures, and potentially leading to disfigurement and decreased
the red sage plant, which is used in traditional Chinese medicine to
treat bone and cardiovascular diseases. Amazingly, T06 inhibits CatK
degradation of soluble and insoluble collagen without affecting other
mobility or independence.1 As a result, the annual economic burden of activities of CatK. With molecular analysis, Panwar et al. predicted that
osteoporosis in Canada is estimated to be $4.6 billion.2 One approach to T06 favorably binds CatK in an ectosteric site, while leaving the enzyme’s
treating this disease has focused on inhibition of the collagen-degrading active site unbound (Figure 1). This anti-resorptive inhibition of CatK
protease capthesin K (CatK). This protein is located in cells responsible was also determined to be reversible upon removal of the compound,
for resorbing bone tissue, both during growth and healing, and in bone and growth of new bone developing cells was not altered by this
wasting diseases. Most of the compounds that effectively inhibit CatK treatment. The latter was demonstrated in cultured cells, as well as in a
bone resorption target the enzyme’s active site, but none of them have mouse model of osteoporosis, where treatment with T06 had no effect on
been approved for clinical use due to negative side effects caused by numbers of bone producing cells but successfully restored bone structure
off-target inhibition of other CatK activities. Researchers in the Bromme and increased bone formation, compared to untreated mice.
lab instead chose to focus on compounds that selectively inhibit the With significant and reversible CatK collagenase inhibition, lack
collagen-degrading activity of this enzyme by targeting a separate of active site inhibition, and therapeutic activity in mouse models of
binding site, the ectosteric site. This approach could make treatments osteoporosis, T06 is a promising compound for the treatment of bone
more therapeutically relevant without the various side effects associated deteriorating conditions. Indeed, the research done by Panwar et al. also
with inhibition of the enzyme’s active site. Their work was published in supports the development of ectosteric inhibitors as a viable alternative
the Journal of Bone and Mineral Research in July 2017. Preety Panwar to active-site inhibitors for treatment of collagenase activity of CatK in
and her colleagues demonstrated the anti bone-resorptive activity of a skeletal diseases.
compound found in traditional Chinese medicine, targeting an ectosteric
1
site in CatK. https://osteoporosis.ca/about-the-disease/
2
The Bromme lab identified the compound Tanshinone IIA sulfonic Osteoporosis International (2016) 27(10): 3023-3032
sodium (T06) in a screen of 31 derivatives of a natural component of Journal of Bone and Mineral Research (2017) 32(12): 2415-2430. C

6
research

Iron Chelation Therapy - A Clinical Front in


the Treatment of MDS Patients?
By USAMA ABBASI, PhD Candidate in Kizhakkedathu Lab

M yelodysplastic syndrome (MDS)


represents a group of diseases often
referred to as bone marrow failure, which
maintaining 3 to 5 grams of iron throughout
their lifespans. Iron is an essential element;
however, it has enormous damaging potential
baseline characteristics and other disease-
modifying drug regimens. In the article, the
authors concluded that “although patient-
usually develops in older people. In Canada when present in excess - it catalyzes free related factors did not differ between iron
alone, up to 6,000 new cases are diagnosed radical generation. Each RBC transfusion chelation therapy and non-iron chelation
each year. The median survival for these introduces an additional 250 milligrams of therapy patients, the receipt of chelation
patients ranges from 0.5 to 6 years after iron into the circulation. Consequently, the was independently associated with superior
diagnosis. increased iron burden eventually causes “iron
In healthy individuals, the bone marrow overload,” imparting toxicity to the transfusion
produces immature blood cells, which recipient; organ dysfunction is a major
subsequently mature into red blood cells complication, with cardiac- and hepatic-
(RBCs), white blood cells, and platelets. In failure accounting for many deaths.
patients with MDS, however, cell development In the October 2017 issue of the British
and maturation is disrupted in the bone Journal of Haematology, CBR investigator
marrow and results in insufficient numbers of and staff hematologist, Dr. Heather Leitch
healthy blood cells in circulation. As a result, (St. Paul’s Hospital), and co-workers analyzed
the majority of MDS patients develop severe the Canadian MDS Registry to evaluate
anemia, leukopenia, and thrombocytopenia whether there is superior survival in MDS
(low platelets) and thus may require frequent patients receiving iron chelation therapy
blood transfusions. (ICT). It is worth noting that various MDS Figure 1. Overall survival from red blood cell
Due to the diversity of MDS, the standard registries previously indicated that RBC transfusion dependence by receipt of iron chelation
of care for patients is constantly changing. transfusion dependence – and subsequent therapy in all patients
Although more aggressive forms of treatment iron overload – are associated with inferior survival.” (Figure 1.)
are available for high-risk subgroups, such overall patient survival. Further, analyses have This prospective study provides
as stem cell transplantation, chemotherapy, documented an association between receiving additional evidence in support of chelation
or hypomethylating agents, the mainstay of iron chelation therapy and superior overall therapy conferring clinical benefit to
treatment is supportive care. This consists of survival. All of these studies of ICT in MDS to transfusion-dependent MDS patients,
transfusions which temporarily elevate the date, however, did not control for potentially although Dr. Leitch and coworkers recognize
number of healthy cells in circulation – RBC confounding variables. that a randomized, placebo-controlled clinical
or platelet transfusions. A review was conducted by Leitch and trial will be able to definitively address the pros
A major side effect of repeated co-workers of prospectively collected data and cons of chelation in MDS.
RBC transfusions is the development of accounting for patient-related factors, such
transfusion-dependent secondary iron as patient frailty, comorbidities and pre- British Journal of Haematology (2017)
overload. Humans are unique in that they existing disabilities. A match pair analysis was 179(1): 83-97. C
lack a proper iron excretion pathway while also performed to account for differences in

7
research

Using Human Kidney Organoids


to Model Disease
B y I D O R E FA E L I , P h D C a n d i d a t e i n M c N a g n y L a b

Section of a human kidney organoid

T here is an urgent need for curative therapies to treat kidney failure. In


2015, over 21,000 patients in Canada received dialysis to treat kidney
failure. Another 2,500 patients received a kidney transplant and 215 died
in vivo. When they are explanted from the kidney into culture conditions,
they dedifferentiate, thereby losing their characteristic cytostructure. And
so, experimenting on podocytes in culture is useful to an extent, but
on the waiting list.1 ultimately, critical findings have to be validated in animal models.
As part of an ongoing collaboration, the laboratories of Dr. Kelly M. Podocytopathies are a group of kidney diseases that primarily affect
McNagny (UBC, CBR PI) and Dr. Benjamin S. Freedman (University of podocytes. For many individuals diagnosed with a podocytopathy, this
Washington) have demonstrated that human kidney organoids grown very likely means a one-way-ticket to end-stage kidney disease. Part of
in a culture dish can accurately model kidney development and disease. the reason why there aren’t many treatments for podocytopathies today is
This work, recently published in Stem Cells,2 is a culmination of decades because of our inability to study these cells in isolation.
of fundamental research into mammalian kidney and stem cell biology. In fact, kidney research has largely been conducted using human
Kidney organoids are multi-cellular aggregates that form structures nearly subjects, rodents or other animal models. Unfortunately, it is logistically
identical to human kidney nephrons with respect to size, architectural difficult to scale the number of human subjects needed to achieve
complexity, and cellular makeup. Importantly, these organoids can be population-level statistical significance in a study. Moreover, there are
generated from patient-derived cells. While there is still a lot of work to unavoidable species-specific differences between rodents and humans
be done to optimize this system, human kidney organoid technology that can sometimes hinder the translation of insights from animal models
promises to expedite kidney research. In the short term, these methods to the clinic. Missing for a long time in the field was a technology that
will allow for more rapid screening of drugs. In the future, this technology would catalyze nephrology research by being both higher throughput and
may provide custom “replacement parts” for patients with failing kidneys. species-specific.
Human kidney organoids are derived from induced pluripotent stem In this recent work, the multi-disciplinary research team showed
cells (iPSCs). iPSCs are cells which have been genetically reprogrammed that podocytes from kidney organoids can recapitulate most of the
to express four key transcription factors that cause them to revert back to developmental progression and structural characteristics of podocytes
a pluripotent state. Once generated in the dish, iPSCs can, in theory, be found in both mouse and human kidneys. Next, they generated mutant
directed to differentiate into all of the cellular lineages and tissues of the organoids using the CRISPR/Cas9 gene-editing system and compared
body. them to mice bearing the same mutation. What they found opens up many
A single human kidney is composed of millions of basic functional new opportunities for the use of kidney organoids as a model system;
units, called nephrons, whose predominant function is to filter blood they showed that mutant podocytes from human kidney organoids
plasma to form concentrated urine. Because of the kidney’s cellular and exhibit near-identical phenotypes to mutated podocytes in the mouse.
architectural complexity, it has long been a challenging endeavour for This finding demonstrates that human kidney organoids are a relevant
scientists to study its cells in isolation; the biological function of kidney system in which to model podocyte biology and disease. That they are
cells depends on continuous reciprocal interactions with other cells and derived from human cells circumvents the issue of species-specificity,
the interstitial fluids of the kidney. and since they are relatively cheap and readily accessible to experimental
An especially difficult-to-study kidney cell type is the podocyte. manipulation, human kidney organoids offer a high throughput model
Podocytes are analogous in structure to octopuses: they have a large cell system.
body, which branches out into many little ‘tentacles’ called foot processes
1
that interdigitate with those of neighboring podocytes to form a sieve-like Canadian Institute for Health Information https://secure.cihi.ca/
structure through which plasma fluid passes to form urine. The reason for estore/productFamily.htm?locale=en&pf=PFC3380
2
their notoriety is that podocytes can only be found in their native structure Stem Cells (2017) 35: 2366–2378 C

8
research

Innate Defence Regulator Peptides:


An Anti-Inflammatory Therapy?
B y K A T H A R I N E S E D I V Y - H A L E Y, P h D C a n d i d a t e i n H a n c o c k L a b

I nflammation is an important
component of our body’s defence
system, but excessive or inappropriate
production of inflammatory mediators:
IL-6, MCP-1, CXCL1 and reactive
nitrogen species in cultured monocytes/
pathway, which is known to be essential
in PMA-induced inflammation. Peptide
treatment suppressed a subset of
inflammation is the main cause behind macrophages. To study this effect in rhodopsin-like receptor genes recognizing
many human diseases, including vivo, the researchers topically applied pro-inflammatory mediators such
Alzheimer’s, atherosclerosis, and the inflammatory agent PMA to mouse as prostaglandin and histamine. The
rheumatoid arthritis. Immunosuppressive ears, immediately followed by IDR-1002 rhodopsin-like receptors are a major family
therapies are often used to treat such or the nonsteroidal anti-inflammatory of the G-coupled protein receptor (GPCR)
disorders, but these treatments also drug indomethacin. The application of group. Interestingly, under conditions of
increase the patient’s risk of infection. In PMA alone causes the recruitment of bacterial infection IDR-1002 can act on
a recent paper,1 Bing Catherine Wu and inflammatory mediator cells such as one or more unidentified GPCR receptors
Amy Lee of the Hancock Lab identify neutrophils, and leads to visible swelling or to increase chemokine production and
a new potential therapy without this edema within 6 hours of treatment. Peptide neutrophil infiltration,2 which suggests that
downside: Innate Defence Regulator (IDR) treatment significantly suppressed both these peptides may have different effects
peptides. the influx of neutrophils and the observed depending on the inflammatory trigger. In
IDR peptides are synthetic versions swelling. The peptide also reduced the the sterile context, the anti-inflammatory
of Host Defence Peptides, naturally local levels of IL-6, MCP-1, CXCL1, and effect of IDR -1002 is likely contributed by
occurring molecules which modulate the reactive oxygen and nitrogen species. the suppression of an IFN regulatory factor
immune system in addition to having These effects were comparable to those 8–regulated network, which is known to
direct antimicrobial activity (as previously of indomethacin, suggesting potential control central inflammatory pathways.
covered by the CBR). Wu and Lee therapeutic application. While IDR-1002 shows compelling
investigated IDR peptide 1002, which has To understand the function of IDR- anti-inflammatory properties, additional
been previously demonstrated to dampen 1002 in more depth, the researchers then experiments are necessary to confirm the
inflammation during bacterial infection used RNA-Seq to compare the genetic safety and effectiveness of IDR-1002 in
while preserving or enhancing the body’s expression within ear tissue after treatment humans. Wu currently plans to test the
ability to fight infection. However, it with a solvent control, PMA, and both peptide in a more human-like context, for
had not yet been determined whether PMA and the peptide. PMA treatment example in an ex-vivo human skin model.
IDR-1002 would have similar activity was confirmed to increase the expression Hopefully, IDR-1002 or similar peptides
in instances of sterile inflammation not of genes associated with inflammation, can be developed into therapeutics capable
caused by bacteria, such as in arthritis or including cytokine signalling, especially of reducing inflammation in a variety of
atherosclerosis. Using a mouse ear model, IFN-γ, TNF-α, and IL-1 cascade, and class non-infectious diseases without weakening
Wu and Lee discovered that the peptide A/1 rhodopsin-like receptors including the patient’s immune response system.
does indeed have strong anti-inflammatory chemokine receptors. However the PMA/
1
effects in sterile, chemically induced peptide combination downregulated Journal of Immunology (2017) 199:
inflammation. many of these pathways, including genes 3592-3603.
2
The researchers first determined responsible for recruiting inflammatory Journal of Immunology (2010) 184:
that in vitro, IDR-1002 dampened the cells such as neutrophils, and the IFN-γ 2539-2550. C

9
research

Can Temperature Modulation be the Answer


to Extending Platelet Shelf Life?
B y WAY N E Z H A O , P h D S t u d e n t i n D e v i n e L a b

F or every 25 units of platelets collected, 1 unit will be thrown away


due to expiration or storage induced lesions.1 This wastage costs
our health care system approximately 5 million dollars a year. The most
reversed by re-warming the platelets and limiting CT storage to less than
18 hours.3 From this, a method was proposed whereby platelet storage
temperatures are cycled (TC) between 4°C for 11 hours and 37°C for 1
common cause of having to discard units is the short storage life of platelet hour. They hypothesized that any cold induced damage would be reduced
concentrates (PCs). Researchers have proposed an alternative storage during the 1 hour at 37°C. In subsequent murine models, TC stored
condition for platelets in the hopes of extending platelet shelf life. platelets exhibited superiority with respect to in vitro platelet properties
PCs are given primarily to two groups of patients. The first and in vivo recovery compared to CT platelets and RT platelets.4
comprise patients with cancer who are undergoing chemotherapy and In a study published in the November issue of Transfusion, Vostal, J
consequently develop low platelet levels (thrombocytopenia) due to et al. further investigated the TC method by conducting a clinical trial to
the drugs suppressing bone marrow production of platelets. PCs are test the in vivo recovery and survival of TC platelets compared RT and CT
transfused as often as once every two weeks to boost their platelet counts. platelets in healthy human volunteers. Stored platelets were radiolabelled,
The second group comprises patients who are actively bleeding due to a transfused into the volunteers, and the recovery and survival of the platelets
variety of reasons (e.g., post-surgery, trauma, obstetrical complications, were monitored. Similar to the murine model, TC platelets had better in
gastrointestinal lesions) and in whom PC transfusions may help in vivo recovery and survival compared to CT platelets.
achieving hemostasis. In comparison to RT platelets, however, TC platelets had significantly
Currently, PCs are stored at room temperature (22°C) under constant lower recovery and reduced survival, which was inconsistent with the
agitation. There are several problems associated with this storage condition, murine model. The authors speculated that the reasons for this disparity
including a limited shelf life (7 days), a risk of bacterial growth, and a might be attributable to experimental design, platelet handling, and the
progressive decrease in their quality, the latter referred to as “storage lesion.” small sample size (n=10). The authors proposed that TC platelets would
To solve these challenges, researchers are investigating the alternative of be most effective in treating actively bleeding patients who do not require
storing platelets under hypothermic conditions (4°C). Storing platelets in significant prolongation in platelet survival time.
cold temperatures slows down microorganism growth and may increase Temperature modulation is just one of the important factors that
PC shelf life. Furthermore, platelet haemostatic activity is superior in cold- contribute to the outcome of stored platelets. While this paper provided a
stored platelets (CT) compared to room temperature stored platelets (RT).2 glimpse into the complexity of platelet storage and preservation, further
The CT storage method was widely practiced from the 1960s until the procedural development is needed to improve the in vivo survival and
1980s. However, the protocol was replaced by RT storage after it was found recovery of CT platelets.
that CT alters platelet structure, morphology, and activation characteristics,
1
resulting in short post-transfusion circulation survival in patients. American Journal of Clinical Pathology (2015) 143(3): 329-335
2
From previously published work, researchers discovered, using British Journal of Haematology (2017) 178(1): 119-129
3
murine models, that some of the cold induced damage to platelets, such The Journal of Laboratory and Clinical Medicine (1978) 92(6): 971-982
4
as morphologic changes and cell surface glycoprotein clustering, could be Transfusion (2013) 53(6) 1178-1186. C

10
awards

2017-2018 CBR Postdoctoral Fellow & Research


Associate Travel Awards
JULIE KORA

Congratulations to the following award recipients!

A nnually, the Centre for Blood Research offers five travel awards to Postdoctoral Fellows and Research Associates to help make travel
to conferences and academic events more feasible. Any Postdoctoral Fellow or Research Associate may apply, provided they have not
received an award in the last year. Each award offers $1,000 to supplement other funding sources. Throughout past years, recipients have
attended and presented research at a wide variety of conferences and events in far-reaching corners of the country and the world. Upon
their return, awardees write short reports on the conferences they attended and their experiences, which are posted on the CBR website.

Jennifer Grants, Postdoctoral Fellow Meera Raj, Postdoctoral Fellow Peter Bell, Postdoctoral Fellow in the
in the Karsan Lab in the Scott Lab Overall Lab
Attended the 59th American Society of Will attend the 31st Annual Meeting of the Will attend the 3rd Matrix Biology Europe
Hematology Annual Meeting in Atlanta, Canadian Society for Immunology in London, Meeting in Manchester, UK
GA ON July 2018
December 2017 June 2018

Kai Yu, Postdoctoral Fellow in the Natalie Zeytuni, Postdoctoral Fellow


Kizhakkedathu Lab in the Strynadka Lab
Will attend the 29th European Conference Will attend an event in the cryo-EM field in
on Biomaterials in Maastricht, Netherlands 2018
September 2018

11
research

Hancock lab demonstrates the role of a bacterial


starvation response in wound infections
By CORRIE BELANGER, PhD Candidate in Hancock Lab

A ntimicrobial resistance is a serious


global threat, causing treatment of even
minor infections to become challenging
formation in mice. Bacteria missing these
genes were also measured for their ability
to lyse red blood cells and for cytotoxicity
understand more about the mechanisms
used by P. aeruginosa during the formation
of wound infections and has important
and expensive.1 When bacteria are starved against human cells. In this case it was shown implications for the future of clinical
or stressed, they can become resistant to that losing both stringent response genes at treatments. New information in this area can
antibiotics through activation of certain stress the same time reduced cytotoxicity, and led bring to light novel mechanisms for treating
response pathways. This leads to decreased to a decrease in excreted virulence factors. clinically relevant infections. The results of
bacterial metabolism, biofilm formation, This supports previous research indicating this study further support the development
increased production of virulence factors, that the stringent response is important of stringent response-targeting substances as
and ultimately a bacterial growth state that is for bacterial virulence and cytotoxicity, alternative methods to antibiotics to fight the
more resilient and harder to treat.2 In a recent and points to the specific enzymes that are wave of devastating drug resistant pathogens
publication in Frontiers in Microbiology,3 involved. It was further demonstrated that we are currently facing.
members of the Hancock lab explored the targeting the stringent response with small
1
importance of a specific stress response, called cationic peptides DJK-5 and 1018 had a WHO (2014) Antimicrobial
the stringent response, and its mechanism profound effect on the ability of multiple P. Resistance: global report on surveillance.
2
in infection and virulence of a notoriously aeruginosa strains to elicit virulence and Current Opinion in Microbiology
drug resistant pathogen, Pseudomonas wound formation. (2016) 33: 35-40.
3
aeruginosa. Their research indicates that This research allows scientists to Frontiers in Microbiology (2017) 8. C
this stringent response plays a large role
in skin infections, and that treatment with
specific small peptides can target the stringent
response to inhibit the adaptive bacterial
behaviour, thereby overcoming resistance and
virulence in deep skin infections.
Starvation and other stresses that
bacteria encounter in a host environment
can trigger the stringent response in
pathogens after infection. In P. aeruginosa,
this process relies on global stress response
regulator enzymes RelA and SpoT, which
ultimately control the cellular levels of a
nucleotide secondary messenger, guanosine
tetraphosphate (ppGpp) (Figure 1). High
levels of this messenger can alter gene
expression and cause the bacteria to switch
from susceptible growth states to more drug
resistant states, such as biofilms.2
Experiments performed by Pletzer
et al. used bacterial strains that fluoresced
when RelA and SpoT genes were activated
to demonstrate that both stringent response Figure 1. Bacterial stringent response is controlled by enzymes SpoT and RelA, which maintain the
genes were expressed during skin wound cellular levels of signaling molecule ppGpp, and ultimately leads to increased biofilm formation,
antibiotic resistance, and virulence.

12
events

16th International
Conference on Pseudomonas
By DANIEL PLETZER, Postdoctoral Fellow in
Hancock Lab

W ith support provided by a CBR Post-Doc Travel Award, I had the opportunity
to attend the biennial Pseudomonas conference between September 5
and 9, 2017 in Liverpool, UK. This conference primarily focused on bacteria from
the Pseudomonas genus and brought together researchers from all over the world.
During this meeting, various exciting research topics were covered, including
evolutionary biology, infections and host-pathogen interactions, signalling systems,
genomics, and biofilm research related to antibiotics and resistance.
I had the opportunity to present a poster which described a cutaneous murine
abscess model using the important human pathogen Pseudomonas aeruginosa.
This model could potentially be a game changer in the field, since it can be easily
implemented without technical challenges and can be used to study acute and Poster presentation hall
chronic infections. I used this model to treat high-density bacterial infections with
synthetic anti-biofilm peptides developed in our lab. I furthermore showed that
the mechanisms of action of these peptides could be linked to the stringent stress
response in vivo. My work was of significant interest to other attendees at the
conference, and I got a chance to talk with many experts and shared many ideas
while learning about the thrilling work being done by others in the field.
Overall, the conference had a great mix of interesting, inspiring, and insightful
talks and posters. The breathtaking venue of the meeting was at the UNESCO
World Heritage St. George’s Hall, one of the finest examples of neo-classical
architecture in the world. During my trip, I also got a chance to see the city of
Liverpool, the birthplace of the Beatles, and visited numerous tourist attractions,
including the Liverpool cathedral and the Albert Dock. I also enjoyed the local pub
experience and British culinary delights. C
Hotel room in Beatle style (IBIS Styles Liverpool)
View from the harbour.

13
events

Dr. Earl Davie (centre left) and Dr. Eddy Fischer (centre right) with symposium speakers

Earl Davie Symposium 2017: In Review


B y L I LY T A K E U C H I , V I V I E N N E C H A N ,
S T E F A N I E N O VA K O W S K I , a n d E N O L I D E S I LVA

C elebrating the eminent career of Dr. Earl W. Davie, the annual


symposium honours the achievements of a pivotal figure in
medicine whose pioneering discovery of the waterfall sequence of
gene therapy a viable option for patients with hemophilia. After giving
an overview of investigational efforts in adeno-associated vectors (AAV)
for hemophilia B gene therapy, Dr. High began to describe some of the
coagulation has enabled research that led to effective diagnosis, obstacles. During clinical trials, vector, AAV-mediated gene delivery
treatment, and management strategies for numerous blood disorders. of FIX yielded high levels, but the effect was only transient, due to a
Now, Professor Emeritus at the University of Washington, Dr. Davie complex interplay with the immune system. With persistent efforts,
continues to share his passion for science and research, joining local these challenges are being overcome and with the use of highly efficient
and international researchers, students, healthcare professionals, vectors and immune modulation, a majority of patients have retained
patients, and representatives from industry, at the 11th annual Earl Davie factor levels upwards of 30% over 18 months.
Symposium on November 16, at the Vancouver Sheraton Wall Center. Continuing on the topic of hemophilia, Dr. Carol Miao, a former
This interdisciplinary symposium gathered experts in topics ranging trainee with Dr. Davie, presented a talk on novel approaches in
from hemostasis-thrombosis, immunology, and infectious diseases, to hemophilia treatment using ultrasound mediated gene delivery via
vascular biology and cardiovascular research. The director of the CBR, lentivirus. The Miao group has developed FVIII antiviral vectors that
Dr. Ed Conway, gave the opening remarks to introduce Dr. Davie’s career. can be delivered intraosseously to transduce hematopoietic stem cells
Born in Tacoma, Washington in 1927, Dr. Earl Davie started his academic in the bone marrow to produce platelets that can act as a vehicle for
career at the University of Washington. After completing his PhD with factor delivery. Their findings demonstrate that platelets may be an ideal
Dr. Hans Neurath, Dr. Davie moved on to work at Case Western Reserve vehicle, as platelet activation is localized at the site of bleeding.
University School of Medicine. Through his interactions with Dr. Oscar Clinical presentations followed, focusing on the dangers of living
Ratnoff, Dr. Davie’s career took off as he began to characterize a number with “mild” forms of hemophilia and the misconceptions associated
of coagulation proteins. In 1964, in what Dr. Conway described as “a with these disorders. Mr. George Stephenson, an 83 year old patient
foundational discovery that stands the test of time,” Dr. Davie published with “mild” hemophilia, underlined through life experiences that “mild”
a proposal of the famous “waterfall sequence” for blood clotting, marking is truly “sneaky” and can be serious, requiring vigilance in medical care.
a significant advance in our knowledge of coagulation that would pave Dr. Drew Bowie reinforced these concerns from a physician perspective,
the way for many of the research pursuits highlighted throughout the highlighting the need for early recognition and intervention to reduce
symposium. morbidity and mortality.
The first talk of the day was given by keynote speaker, Dr. Katherine Dr. Gow Arepally from Duke University, described the role of
High, on her group’s innovative and exciting strategies towards making complement activation in heparin-induced thrombocytopenia (HIT). Her

14
events

A first for an Earl Davie


Symposium, the CBR’s own Dr.
Conway finally took the stage to
give an intriguing presentation of
work done by his lab to investigate
the link between obesity and
thrombosis. His research group
has revealed that CD248 may be a
novel all-in-one therapeutic target
Poster winners Enoli De SIlva and Guan Guo with Dr. Ed Conway Poster winner Xining (Linda) Yang for treating obesity and venous
thrombosis.
research group discovered that the development of HIT antibodies is Dr. Rodney Camire, from the University of Pennsylvania, presented
dependent on complement activation, revealing new understanding of his intriguing and creative therapeutic strategies, using bioengineered
the immunogenicity of PF4/heparin complexes that may yield novel Factor Xa to treat bleeding disorders in a more controlled fashion. It will
therapeutic strategies. be fascinating to follow the outcomes of the pilot studies planned for
After a brief coffee interlude, attention shifted to sepsis and the patients with major intracerebral bleeds. Finally, we were treated to a
new strategies to combat this global medical emergency. Dr. Bas “fusion” of biology and engineering, when Dr. Abhishek Jain from Texas
Surewaard from the University of Calgary gave an intriguing talk about A&M College of Engineering, introduced the “Organ-on-a-chip.” His
the protective effects of neutralizing Staphylococcus aureus alpha toxin microfluidic devices that mimic the in vivo vasculature hold potential for
(H1a). Dr. Patricia Liaw from McMaster University then shared recent replacing mouse models to evaluate new drugs, as well as mechanisms
advances in targeting cell free DNA (cfDNA) as an approach to treating underlying hemostasis, thrombosis and inflammation.
sepsis. The morning session ended with the signature 30-second Throughout the day, there were all sorts of amazing posters
“shotgun” talks by undergraduate, graduate, and postdoctoral trainees. presented by CBR members at all ages, with judging done by more
Dr. Eddy Fischer, a 1992 Nobel Laureate, led the afternoon with senior members. Award winners for best poster were Xining (Linda)
a reprisal of his presentation from 4 years ago, with a fascinating Yang, Quan Guo, and Enoli De Silva.
overview of how an in-depth analysis of the “archaic” methods used Special thanks to Dr. Ed Pryzdial, Mira Milutinovic, and Julie
to isolate glycogen phosphorylase led to the identification of the Kora, and to the many others who made this event a success. And
components necessary for reverse phosphorylation. The second of course, to our sponsors: Pfizer, Novo Nordisk, Shire, Bioverativ,
keynote, Dr. James Morrissey from the University of Michigan, Canadian Blood Services, CSL Behring, Bayer-UBC Bleeding Disorders
described his groundbreaking work in determining the role of platelet Collaboratory, Octapharma, Grifols, Sheldon Naiman-Linda Vickers
polyphosphate in triggering coagulation and preventing fibrinolysis Endowment Fund, Alexion, New England Biolabs, Stago.
though its interaction with multiple steps in the “waterfall sequence.” Dr. To see recordings and photos from the event, visit the CBR website:
Morrissey is a frequent visitor to the CBR, with several collaborations http://cbr.ubc.ca. To read the Canadian Blood Services’ Research,
that will hopefully lead to the development of safer anti-thrombotic Education and Discovery (RED) blog post about the symposium, visit
therapies. https://blood.ca/en/blog. C
Several PhD students from UBC then had an opportunity to
give short talks. Bryan Lin (Pryzdial Lab) reported how some viruses
Poster presentations at the Earl W. Davie Symposium
promote coagulation through incorporation of tissue factor on their
envelope. Beverlie Baquir (Hancock Lab) described a combined mass
spectrometry and flow cytometry method for identifying and isolating
specific subpopulations of immune cells present during early sepsis.
James Baylis (Kastrup Lab) described a new strategy for treating
severe bleeding during trauma, using self-propelled microparticles
incorporating thrombin and tranexamic acid.
Sheila Walker and her daughter, Holly, shared their inspirational
stories of a familial thrombotic disorder. Holly suffered a thrombotic
episode that affected her ability to control emotions. In spite of this, she
is facing the challenge, continuing to fulfil her passions: skiing, climbing,
and helping others.

15
opinion

When Evidence is Not Enough:


Pro-Vaccination Strategies
B y K A T H A R I N E S E D I V Y - H A L E Y, P h D C a n d i d a t e i n H a n c o c k L a b

A long with antibiotics and sanitation,


vaccines are among the cornerstones
of modern medicine, preventing or even
concerned for their children’s safety but that
will not unduly burden those parents already
struggling to get their children vaccinated.
body’s natural defenses, or using the term
“community immunity” instead of “herd
immunity.” Staunch anti-vaxxers comprise a
eradicating diseases and saving countless Strong legal pressure also risks backlash small proportion of the population,2 and yet
lives.1 Despite overwhelming evidence among anti-vaccination movements. their tendency to cluster can create risks of
in favour of vaccination, immunization Some experts argue for “compulsory local outbreaks. Still, even communities with
rates have fallen, in some areas below the informed choice,”2 rather than compulsory a vocal anti-vaccination faction likely include
thresholds necessary to protect against vaccination, requiring parents to actively many quietly pro-vaccination parents;
outbreaks of diseases, such as measles.2 Why decide against vaccinating their children. pointing out the number of dissenters may
do people reject vaccination, and what can Requiring individual counseling prior dilute anti-vaccination social pressure.5
be done? to refusal would offer an opportunity to Finally, creating a national registry of
Concerns about vaccine safety are communicate the benefits of vaccination vaccination status would make it easier to
commonly cited in the media. While these and address concerns about safety. Advice identify areas at risk for disease outbreak,
concerns can be based on misunderstanding of health care providers – doctors, nurses, target interventions, and communicate with
or lack of education,3 parents with strong and midwives – can have a great deal of parents early and often about gaps in their
anti-vaccination convictions are often well influence over parents, and specific strategies child’s vaccination status.2 In combination,
educated,4 but may mistrust the government can increase vaccination acceptance.6 these strategies would promote vaccination
or the medical industry and want to make Healthcare workers should elicit individual and keep our communities safe from
their own decisions about healthcare.5 concerns about vaccination and specifically preventable diseases.
Practical concerns and socioeconomic address those concerns, debunking myths
1
barriers, such as lack of access to clinics, have and providing a balanced assessment of Proceedings of the National Academy of
also been implicated in non-vaccination the risks and benefits in terms that parents Sciences (2017) 114: 4031–4033.
within Canada2,3 and lower-income and can understand. Anecdotes illustrating the 2
A Shot in the Arm: How to Improve
rural groups in the United States.4 consequences of diseases may be useful if Vaccination Policy in Canada (2015).
3
The first step in improving vaccination they can be framed positively in terms of Human Vaccines & Immunotherapeutics
rates is to adjust practical factors so that it is protection; inducing fear in vaccine-skeptical (2017) 13: 1447–1453.
easier to vaccinate than it is to not vaccinate. parents can backfire.7 4
Pediatrics (2004) 114: 187–195.
5
Barriers should be removed – for example, Parents who are strongly against Medical Anthropology Quarterly (2015)
extending clinic hours or offering home visits vaccination are likely to dismiss evidence 29: 381–399.
– and opting out of vaccination should be contradicting their views.7 To break through 6
Paediatrics & Child Health (2013) 18.
7
made more difficult. Mandating vaccination their opposition, it is necessary to target Pediatrics (2014) 133: 1–8.C
is an imperfect solution, as it is difficult these parents’ world views, for example, by
to find incentives that will sway parents emphasizing how vaccines stimulate the

16
awards

2017 Michael John Page Postdoctoral Fellow Award


JULIE KORA

O n Thursday, October 26th, the Department of


Biochemistry & Molecular Biology, along with the Centre
for Blood Research (CBR), presented the fifth annual Michael
John Page Postdoctoral Award to Dr. Jürgen Niesser, a
postdoctoral fellow in Dr. Natalie Strynadka’s lab. The Michael
John Page Postdoctoral Fellow Award, established in 2013,
honours the memory of UBC alumnus, Dr. Michael John Page.
This award recognizes a Postdoctoral Fellow who reflects Dr.
Page’s academic excellence and his passion for life.

Dr. Ross MacGillivray and Roger Page (Michael Page’s father)


presented this year’s award at a ceremony where Jürgen
gave a lively and humorous talk to a receptive audience,
followed by an award reception. Jürgen’s talk was entitled,
“Blurring the Lines between Fun and Science,” highlighting
his academic journey thus far (complete with many stories of
lab member camaraderie and antics). Jürgen earned his PhD
in Biochemistry and Structural Biology with Patrick Cramer
at the University of Munich and the Max Planck Institute
for Biophysical Chemistry in Göttingen, Germany. Currently,
Jürgen (L) with Evan Haney (R), 2016 award recipient Jürgen’s work in the Strynadka lab focuses on multiple novel
target-inhibitor complexes related to cancer and neurological
disorders. (To view photos of the award event, visit the CBR
Facebook page.) C

About Dr. Michael John Page: Michael John Page was born and raised in Thunder Bay,
Ontario, where he graduated from Port Arthur Collegiate in 1994. He attended Carleton
University in Ottawa, graduating with his B.Sc. in Biochemistry in 1998. Following, he
entered the Biochemistry & Molecular Biology graduate program at UBC under Ross
MacGillivray’s supervision. During his graduate studies, his fellow students recognized
Mike’s achievements by selecting him for the prestigious 2001 Zbarsky Prize. He then
completed a highly productive postdoctoral fellowship, studying the biological activity of
thrombin with Dr. Enrico Di Cera at Washington University in St. Louis, and in 2010, moved
to a junior faculty position at the University of California, San Francisco, mentored by Dr.
Charles Craik. Tragically, Mike died suddenly in June 2013 at age 36, leaving a legacy of a
thirst for knowledge and a love of life.

Thank you to New England Biolabs, the Page Family, and the Department of Biochemistry
and Molecular Biology for their generous support to make this award possible!

Congratulations to Jürgen on receiving this honour! C

Dr. Michael John Page

17
profiles

CBR Member Profile: Deb Chen


JULIE KORA

D eb has been an integral member of the CBR in the Devine Lab


since 2012 and has been involved in numerous activities. On
Monday, November 27th, Deb defended her thesis to earn her PhD.
Outside of the CBR, I was involved with the UBC Centre for Teaching,
Learning and Technology (CTLT) as a graduate facilitator. This
experience was instrumental in allowing me to gain insight into my
Congratulations, Dr. Deb! Read on to find out more about Deb’s own learning process and establishing an interdisciplinary network
insights regarding her academic journey and what she has been up to through working with other graduate students and faculty members.
during her time at the CBR. This was a big anchor for me throughout my graduate studies and my
involvement with CTLT has helped me land my new position as an
Q. In a nutshell, what has been the focus of your research? Educational Developer.
A. My research has focused on identifying protein markers that
may be predictive for the development of storage hemolysis in red Another cornerstone throughout my PhD was the Vancouver Crisis
cell concentrates; that is, the rupture of the red blood cell and its Centre. I have volunteered over 500 hours with the Vancouver Crisis
subsequent release of hemoglobin-rich cytosolic content. Centre since November 2012 and have transitioned to a staff role
training and supporting volunteers in taking calls and chats. I was able
Q. What did you enjoy most about the PhD process? to find meaning and gain perspective through supporting members of
A. I enjoyed the exploration of different learning opportunities, within our local community and through empowering those in distress to help
the CBR and beyond. themselves. In addition to being able to give back to the community,
I discovered beautiful friendships and an amazing support network
I’ve participated in various opportunities within the CBR and have through genuine connections with my fellow volunteers and staff.
been encouraged to develop educational programs for our own
members – from teaching high school students through our Blood I was also involved with Students for Science-Based Medicine, a MUS/
Labs Outreach program, writing a few posts for the KT committee, AMS club at UBC, translating scientific findings in literature for the lay
planning social events with the Health & Wellness committee, to public related to alternative and complementary medicine. Through
designing and delivering science writing and 3MT workshops. the delivery of educational workshops and free public events, we
I’m grateful that the CBR Educational Program offered so many were able to engage in critical discussions with members of our local
opportunities to meet my learning and professional development communities about how to make informed decisions related to health
needs. and how to ask critical questions.

18
profiles
The theme of all that I’ve done relates to people. The reason for my continual involvement in these
exploratory undertakings has been because of the people I’ve worked with; they’ve challenged me
to grow within my various capacities, embraced my mistakes, and celebrated my risk-taking and
achievements.

Q. What insight can you provide into the job search experience for others who are
finishing up a graduate degree?
A. I devoted a lot of time every day to browsing jobs and connecting with my existing network to
help me identify my strengths and to articulate what I wanted for my next step. This has been a
process where I’ve needed to be persistent in continually looking for opportunities and letting my
network know what I wanted to do. Your network holds you accountable and can direct you to
opportunities you might not otherwise have access to.

My approach was to dedicate at least 1 hour every day during the thesis writing process to figure out
all of these career pieces and how they aligned with what I wanted to do.

Q. What has been the most valuable thing you’ve gained from your experience at the
CBR?
A. The network, the people, and the opportunities that came with the CBR as a package that I’ve
been happily exploiting.

Q. What advice do you have for current grad students, knowing what you know now?
A. Try things that scare you. Create protected time to explore things that might not be fully
aligned with your research (within reason of course; I don’t want to get you in trouble with your
supervisors). Be open and curious about new opportunities, because you never know how the
things you learn or gain (whether that’s a skill or an insight into yourself) may inform or support
your future goals.

Q. What has helped you maintain work/life balance?


A. Connecting with friends, hiking, bouldering, running, cycling, reading (NOT academic articles).
It was a process to not take myself so seriously and to not put so much emphasis on my “success.” I
worked on not letting my research results influence my emotions and on leaving my research on the
bench during evenings and on weekends. Seeking out activities that helped me find meaning in the
work I’m doing has given me perspective, as well as my engagement in roles outside my research.
I don’t think it would have been possible for me to gain these perspectives if I had only focused on
my research alone.

Q. What’s your favourite ice cream flavour?


A. Currently, cardamom from Earnest Ice Cream.

Q. If you had a superpower, what would it be?


A. The ability to warp time so that I could have more sleep!

Q. What is a little known fact about you?


A. My roommates and I keep three chickens. Their names are Eggness, Korlis, and Meryl.

Deb would be happy to answer your questions and to share her experiences with graduate students.
She can be contacted at debchen@mail.ubc.ca. C

19
events

CBR Labs Attend the 10th General Meeting of


the International Proteolysis Society
By DR. GEORGINA BUTLER, Research Associate in Overall Lab

P roteases are an important class of enzymes that cut every protein in


the body at some point in its lifetime – be it for maturation of new
proteins, degradation of unwanted proteins, and for precise trimming
Tissues, and TAILS Proteomic Substrate Discovery: Data Analysis (run by
CBR’s own Chris Overall, PDF Dr. Nestor Solis, and former PDFs Dr. Ulrich
auf dem Keller and Dr. Oliver Schilling). A large number of travel awards
and regulation. Proteases are key for homeostasis — in fact hemostatic are also presented to trainees.
processes such as coagulation and fibrinolysis depend on them — and Talks addressed a variety of topics including protease structure,
proteases are implicated in many diseases, including hemophilia, cancer, with elegant structures describing the snap-trap mechanism of a serpin
and arthritis. Accordingly, humans have over 560 proteases and 160 (Dr. F.X. Gomis-Ruth, Barcelona, Spain) and of angiotensin-converting
protease inhibitors, and these are linked in complex interdependent enzyme dimerization (Dr. E. Sturrock, Cape Town, South Africa), with a
networks. large focus on development of tools for studying protease function and for
This fall, the Overall and Bromme labs attended the 10th General protease inhibitors (e.g., fluorescent probes for imaging serine proteases
Meeting of the in neutrophils
International (Dr. P.
Members of the Overall Lab
Proteolysis Kasperkiewicz,
Society. In Sanford-
previous years, Burnham, USA),
this biennial design of PCSK9
get-together of antagonists
200 protease (Dr. Daniel
researchers Kirchhofer,
has been held Genentech,
in such exotic USA), inhibitory
climes as mechanism
South Africa of a cathepsin
and Malaysia. K inhibitor
This year, (Simon Law,
the meeting, CBR, Canada),
organised by and engineering
Prof. Chris enhanced FIX
Overall (CBR), variants (Dr. G.
Dr. Joanne Blouse, Novo
Lemieux (U. Nordisk A/S,
Alberta), and Denmark)).
Dr. Jean-Bernard Denault (U. Sherbrooke), was held at the Banff Centre Highlights of the meeting included fireside line dancing and BBQ on
in Canada (28 Oct-2 Nov 2017). One of the great things about these the first evening (which somehow incorporated a conga), an impromptu
meetings is that they are preceded by training workshops, where experts snowball fight, and a fun Halloween poster session, where barriers
in the protease field mentor aspiring young scientists – in this case, between experts and novices were broken down when it was impossible
workshops held at the University of Calgary were Hands-on Practical to determine who you were talking to! C
Enzyme Kinetics, A Beginners Guide to Imaging Peptidases in Cells and

20
opinion

To Transfuse or Not to Tranfuse?


B y K A T E S E D I V Y - H A L E Y, P h D C a n d i d a t e i n H a n c o c k L a b

T hanks to their dramatic lifesaving effects, blood transfusions have


become commonplace in modern medicine. However, it is only
in the last two decades that clinicians have begun to assess whether
methods require refinement.
Transfusions can also carry risks beyond those associated with
blood-borne pathogens. Researcher Majad Rafaai from the University
transfusions actually improve patient outcomes under the existing of Rochester, says that whole blood should be considered a “liquid
standards and procedures. The results: blood transfusions may be “too organ,”1 as it contains a variety of heavily regulated and specialized cells.
much of a good thing”1 for patients with less severe blood loss. Introducing foreign cells via a blood transfusion can have harmful
The risk of infection from blood-borne pathogens2 is a familiar effects, similar to those observed in solid organ transplantation. The
one. Currently, this risk is reduced (though not eliminated) using both age of donated blood may also prove detrimental in blood transfusions,
donor questionnaires to select for donors with low pathogen risk and though the research is not yet conclusive. During storage, red blood
biological tests to detect pathogens. While biological testing is effective, cells can become misshapen and rigid, impeding proper circulation
testers need to know what types of pathogens to look for. For example, through small blood vessels. Stored cells may also deteriorate, releasing
in the early 1980s, public health officials did not recognize that HIV substances such as iron, which feeds bacteria and increases the risk that
could be transmitted through blood transfusions until an infant had invading bacteria will proliferate.
been infected by contaminated blood.3 Even after a blood-borne Considering the multitude of complications that may arise,
pathogen has been identified, a screen must be developed to properly transfusion is an unnecessary risk for many patients. The AABB
assess donated blood. When the Zika virus first emerged, a screen (formerly the American Association of Blood Banks) has recently
was not available and blood banks in at-risk areas were forced to stop revised its guidelines4 based on 31 clinical trials investigating outcomes
taking donations completely. Prions – misfolded proteins which cause such as mortality, infection, and stroke. To reduce the risk of adverse
diseases such as Creutzfeldt-Jakob – are also difficult to detect in the outcomes, the AABB now recommends that for most patients, red
blood supply. In circumstances where a proven screen is in place, the blood cell transfusions should only be administered when the patient’s
added cost of testing can still lead to insufficient screening. The parasite hemoglobin drops to 7-8 grams per decilitre (compared to the previous
Babesia microti is one such example and has caused at least 27 deaths standard of 9-10 grams per decilitre). For some patients, alternatives
since 1979 through contaminated transfusions. A screen was developed to blood transfusion may be available. Anemic patients may be treated
in 2012 but is still not widely used, as it can increase the cost per unit of with intravenous iron, and measures can be taken to reduce blood loss
donated blood by 7-10%. Uninfected blood platelets can also become during surgery. In contrast, some patients have a greater need for the
contaminated with bacteria during handling, resulting in potentially oxygen that blood provides. Patients with heart or brain injuries, or
fatal sepsis in the recipient. chronic illnesses may still need more liberal transfusions.
To remove pathogens we don’t know how to look for, pathogen- With blood transfusions being an integral part of many areas
reduction systems can often be effective. This emerging technology of medicine, more research is needed in order to better understand
removes all known and unknown bacterial, viral, and parasitic the principles of transfusion and assess the needs of different patient
contaminants from donated blood. Samples are treated with a molecule populations. Eliminating unnecessary transfusions will not only reduce
that binds nucleic acids and, when exposed to UV light, forms cross- patient risk, but ultimately simplify patient care and decrease stress on
links which prevent cells from reading their DNA and RNA. This blood banks.
1
process does not damage plasma, platelets, or red blood cells, which all Nature (2017) 549: S22-S23.
2
lack DNA and RNA. However, the technique fails to remove prions and Nature (2017) 549: S19-S21.
3
does kill DNA and RNA-containing white blood cells. Thus, it cannot be HIV And The Blood Supply: An Analysis Of Crisis Decisionmaking
used in transfusions containing this cell type. While this new technique (1995).
4
is useful in reducing the risk of infection, its scope is limited, and the JAMA (2016) 316(19): 2025. C

21
events

CBR Visits STEMCELL Technologies


By CORRIE BELANGER, PhD Candidate in Hancock Lab

R ecently, a lucky group of 26 PhD students and postdocs from the


Centre for Blood Research (CBR) attended an all-inclusive tour of
STEMCELL technologies. This event, organized by the CBR Educational
Conder. This broad range of representatives demonstrates the scope
and skill set required for such a large organization to succeed. Notably,
the company aspires to fill their positions primarily with people
Program, was a great opportunity to meet and network with various possessing scientific backgrounds. Even the sales and marketing reps
professionals and to learn what a career at STEMCELL Technologies or are expected to understand how the company’s materials are used and
other similar biotech companies would look like. are thus trained to troubleshoot customer issues in any situation.
Originally launched in 1993 as Terry-Fox Laboratories, STEMCELL The STEMCELL research facility comprises approximately 200
Technologies has become the largest biotech company in Canada. They people, divided into ~20 teams, each working on their own project.
currently employ over 850 people in Vancouver alone and estimate Given the confidential nature of much of the work, we very much
that this number will grow to 1700 by 2020. The company has three appreciated that two senior technicians could take us on a tour of the
locations in Vancouver and also employs scientists in 11 other countries product research and development labs.
around the world, including France, Australia, China, and Singapore. Finally, after an amazingly stimulating and informative morning of
Globally, STEMCELL has made a name for itself by producing high talks, we had the opportunity to speak one-on-one with several of the
quality specialty cell culture media, developing cell isolation systems, company representatives during a catered lunch.
and providing accessory products for stem cell and tissue culture The tour of STEMCELL Technologies was a great opportunity
research. for many CBR members to learn from and make connections with
The CBR group was welcomed at the Head Office and Research successful scientists in the biotech industry. In particular, Nadya from
Building in Vancouver where they were introduced to a few of the the sales department, encouraged us all to build and enhance our
company’s heads and managers, given a brief peek into the labs, scientific careers by always trying different things. You never know
and then offered a lunch and networking session with some of their where any one of the experiences you encounter will lead you. If CBR
representatives. Speakers included Chief Commercial Officer Andrew members can take away one thing from this networking opportunity,
Booth, Marketing and Communication Publishing Manager Nicole it is that the biotech industry offers multiple career directions, and it
Quinn, Global Sales Trainer Nadya Ogloff, Process Development is therefore important to acquire a wide range of skills during training,
Manager Stephen Fussey, Manufacturing Representative Beatriz which will inevitably yield many more opportunities along the way. C
Rodriguez, and Research and Development Senior Scientist Ryan

22
events

Travel Award Summary: 59th American Society


of Hematology Meeting and Exposition

By JENNIFER GRANTS, Postdoctoral Fellow, Karsan Lab

W ith support provided by a CBR Post-Doc Travel Award, I had the opportunity to attend the 59th American
Society of Hematology Meeting from December 9th to 12th in Atlanta, GA. This is one of the most
comprehensive international hematology conferences and attracted approximately 20,000 hematology researchers
and physicians. The meeting covered various exciting topics, including molecular mechanisms in normal
hematopoiesis and in hematological disease, novel therapies, and clinical trial reports.

I had the opportunity to deliver an oral presentation describing a single-cell-resolution study of hematopoietic stem cell (HSC) function
in a mouse model that exhibits chronic inflammation due to loss of a gene commonly deleted in myeloid leukemia patients. My study
provided evidence that this genetic lesion, which affects a gene called miR-146a, can alter HSC function and cell population structure far prior
to the onset of overt disease symptoms, and that reducing inflammation can prevent this HSC dysfunction. These results provided insight
into the mechanisms by which miR-146a loss initiates myeloid leukemia, and suggested that myeloid leukemia patients with loss of miR-146a
could potentially benefit from anti-inflammatory drugs in addition to standard chemotherapy.

My work was of interest to other attendees at the conference, and I had the excellent opportunity to discuss my results and share ideas
with other researchers in my field. C

23
events

CBR Paddleboarding Extravaganza


By ARJUN BAGHELA, Masters Student in Hancock Lab

E ach month, the Health and Wellness Committee (H&W) of the CBR
organizes a fun activity for CBR members to leave their bench, learn
new skills, and exercise. On September 12th, they all ventured down to
group had polished through the snacks. Moments passed before
the group noticed that Abhinav Kumar and Marta Ordoño, graduate
students in the Côté lab, had not made it to shore with the rest of the
Jericho Beach for a relaxing evening of paddleboarding at the Jericho group. It seemed as though Abhinav and Marta were not able to fight
Sailing Center. the combined forces of the choppy waves and certain shamelessly
Everyone arrived, ready to jump onto a paddleboard and voyage hungry students. After several minutes of only slightly frantic searching
through Vancouver’s harbour. After thoughtfully selecting the right (the onshore group started feeling rather sleepy), the pair was spotted
paddleboard, we took to the ocean. Sam Hinshaw, a graduate student in the far distance, slowly, but surely, paddling toward the shore. It was
and notorious show-off in the Hancock lab, entered the water with a close call, but thankfully the $30 dollar rescue fee did not need to be
ease and quickly paddled away. The rest followed cautiously, as the spent!
ocean currents were choppier than expected. After several paddles, The sight of the North Shore Mountains, Vancouver’s skyline,
most CBR members became comfortable maneuvering the board and the setting sun made for a memorable experience on the water.
through the waves and coincidentally began to warm up to Sam again. The minor incident involving the brief disappearance of two group
Many members even had the courage to stand up on the paddleboard members was quickly forgotten by all but Abhinav and Marta. After
and drop into oncoming waves like professionals. There was a all, the CBR’s paddleboarding excursion was a great bonding activity in
noticeable camaraderie growing amongst the group as we explored a beautiful, marine backdrop. Sarah Mansour of the Hancock lab even
Vancouver’s harbour in this somewhat unconventional way. claims she was greeted by a pod of orcas that, shockingly, no one else
As appetites grew stronger, the hungry CBR members began witnessed. Naturally, Sam Hinshaw recounted a tale of single-handedly
making their way back to shore for some well-deserved snacks fighting off a great white shark. This surprised no one, of course.
and refreshments, generously provided by the H&W Committee. Many thanks to Bernard with Windsure Adventure Watersports
Approximately two and a half minutes upon landing on shore, the for his paddleboarding guidance and assistance! C

CBR Paddleboarders

24
partnership

The Bayer-UBC Bleeding Disorders Collaboratory


Continues to Innovate
B y K A T E S E D I V Y - H A L E Y a n d L I LY T A K E U C H I

T he Bayer-UBC Bleeding Disorders Collaboratory, established in


2012 with a $750,000 financial commitment from Bayer Inc.,
has stimulated substantial innovation in the treatment of hemophilia
care, which includes mindfulness training, a peer counsellor, and
combined pediatric-adult clinic visits, to ensure continuity of care.
Improved transition to the adult program may be particularly helpful
and other bleeding disorders by integrating and supporting programs for patients with mild hemophilia, who may not need regular visits to
at the Centre for Blood Research at UBC, St. Paul’s Hospital, and BC the adult clinic but would still benefit from support in managing their
Children’s Hospital. As a whole, the Collaboratory has increased bleeding and social issues. The Collaboratory has also funded a one
communication between researchers, clinicians, and patients, and year fellowship to address a gap in training for physicians specializing
empowered patients to monitor and prevent bleeding. in hematology.
With the support of the Collaboratory, the CBR has improved In the first three years of the Collaboratory, the provincial
its capacity to share knowledge among multiple groups: between adult bleeding disorders program at Saint Paul's Hospital, directed
experienced researchers and trainees, basic and clinical researchers, by Dr. Shannon Jackson, achieved an 85% decrease in bleeds in
and between researchers and the community. The Collaboratory patients with severe hemophilia A. Not only does preventing bleeds
supports graduate students and undergraduate summer students improve patient health in the short-term, but it also avoids or delays
involved in blood research. It also provides funding for seminars, complications, such as joint arthritis, which can have a serious long-
the CBR Research Day for undergraduate students, the Earl Davie term impact on quality of life. The program attributes this success to
Symposium, and the Norman Bethune Symposium. The Earl Davie an increased capacity for individualized care, with a focus on patient
Symposium is attended by basic scientists, clinicians, and patients, autonomy. With this strategy in mind, the program is developing
and in 2017 hosted talks on the topics of hemophilia, coagulation, new mobile and digital technologies to help monitor patient bleeds,
thrombosis, inflammation, and sepsis. The internationally recognized deliver immediate feedback on overall joint health, and provide rapid
Norman Bethune Symposium similarly brings together clinicians, access to health information. These technologies will enhance patient
students, scientists, and para-medical personnel, and will be next held participation in managing their bleeding disorders: a perfect example
on April 10, 2018. of personalized medicine at work!
Under Dr. John Wu's direction, the comprehensive provincial Ms. Sarah Mink, Business Relations Manager at Bayer, says,
pediatric bleeding disorders program at BC Children's Hospital “Bayer is unique in that they really show a commitment to the
sets improvement-oriented goals with strong support for and hemophilia community, and this partnership is reflective of a desire
communication with parents and adolescents. Collaboratory to collaborate and innovate patient care outcomes... Bayer is really
resources have allowed the pediatric program to examine patterns hoping to offer support at all levels for the hemophilia community.”
of bleeds so as to better prevent and manage them. As part of this Thanks to this support, the Bayer-UBC Bleeding Disorders
process, point of care ultrasound is now used to detect bleeds and Collaboratory is indeed a leader in the innovation of patient care
show young patients the internal effects of a bleed. Adolescents and strategies, and a model for similar collaborations worldwide. The CBR
young adults benefit from improved patient transitions into adult is fortunate to have such a wonderful partner in Bayer!C

25
awards

Dr. Jayachandran Kizhakkedathu


Receives Faculty Research Award
JULIE KORA

Congratulations to Dr. Kizhakkedathu on


receiving this prestigious award!

D r. Jay Kizhakkedathu is a
Professor and researcher
in the Department of Pathology
and Laboratory Medicine, an
Associate Member with the
Department of Chemistry, and
a member of the Centre for
Blood Research (CBR) at the
University of British Columbia
(UBC). His research focuses on
the themes of macromolecular
therapeutics, cell-surface
engineering, proteomic
reagents, and blood-compatible
Dr. Jay Kizhakkedathu
surfaces and devices. Dr.
Kizhakkedathu has recently been awarded the 2017 UBC Killam Research Prize, which recognizes
outstanding research and scholarly contributions to a variety of fields. Dr. Kizhakkedathu will
receive this honour at an awards reception, held on April 17, 2018 in the Chan Centre at UBC.

The UBC Killam Research Prizes are awarded on an annual basis to full-time faculty
researchers who demonstrate excellence in their fields. Five awards are available in the area of Arts
and Humanities, and five are reserved for Applied Science and Medicine. Faculty members are
nominated for awards by two to three tenure track faculty members who illustrate how candidates
have impacted their research fields.

In addition to the Killam Research Award, Dr. Kizhakkedathu received the UBC Faculty
of Medicine Distinguished Achievement Award in 2013, was recognized as a Michael Smith
Foundation for Health Research Scholar in 2011, and received the Department of Pathology and
Laboratory Medicine Excellence in Research and Discovery Award in 2011. Dr. Kizhakkedathu was
also honoured with the Canadian Institutes of Health Research New Investigator award in 2005.
His research has been published in numerous science journals, including Science Translational
Medicine, Nature Materials, Nature Biotechnology, Nature Communications, Blood, Journal of the
American Chemical Society, Biomaterials, and many others. C

26
profiles

Interview with Ross MacGillivray, CBR Founding Director


By DR. SARA SABERI, member of Côté Lab

R ecently, Dr. Ross MacGillivray, Professor of Biochemistry and


Molecular Biology and one of the founding members of the CBR,
retired after almost 37 years of work and dedication. Dr. MacGillivray
Q. What are your plans for your retirement?
A. I will stay as Chair of the Biosafety Committee and keep my office
for a while; plus I will keep reading the Nature magazine. I love golf
served as the first Director of the CBR. His research focused on human and traveling to new places like Australia and Africa, as well as places
blood proteins involved in coagulation and iron homeostasis. We we have been in the past and would love to get back to again, like Italy.
interviewed him about his experience during all these years and asked I also have a totem pole in the garden that needs to be finished. And of
him about his retirement plans. course, my major hobby is soccer, which I always watch and cheer for
the Whitecaps. I also would like to be a pilot, but these days everything
Q. How did you become a Professor at UBC? is done by auto-pilot. Not much is done manually, by the pilot himself,
A. At that time, I applied for faculty positions at four different unless there’s an emergency, which takes the fun out of it.
universities. Actually, UBC was the only one that I got an interview
for, and I got an offer. I Q. What has been the
remember that I accepted best part of your life?
the UBC offer at Christmas A. Family always comes
time, around 36-37 years first, and, as part of that,
ago. having kids was the best
experience. I had my kids
Q. How would you when I was 39 years old,
describe your years of and this allowed me to
work and life at UBC? spend a lot of time with
A. I have had a wonderful them.
career and life here at
UBC and in Vancouver in Q. What is a favourite
general. I enjoyed teaching memory you could
a lot and believe that share with us from all
teaching keeps you young. these years at work?
I have always believed in A. Friday’s TGIF events
young scientists and the were the best! Drinking
importance of fresh blood beer and wine while
in academia. interacting with people
from different departments
Q. What is your key to Dr. Ross MacGillivray with Dr. Earl Davie on a regular basis was the
success in work? best part.
A. My success is due to trying to work with people with minimum
conflict. The key to this is communication. I have always supervised We would like to thank Dr. Ross MacGillivray for the time he dedicated
people in a way that I would have liked to be supervised. I believe that to this interview and the many years he has devoted to the CBR. We wish
there is enough space in science for everyone to be successful, and there him a joyful and relaxing time in retirement! C
is no need to compete and put people against each other. I also always
felt blessed to have been able to work with my lab managers, Valerie
Smith and Jeff Hewitt, for 20 years.

27
We thank all our donors from academia, industry, and
the private sector for your generous contributions. cbr.ubc.ca

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