Escolar Documentos
Profissional Documentos
Cultura Documentos
ALZHEIMER’S DISEASE
EVENT HIGHLIGHTS
APRIL 2019
MEMBER PROFILES
ADVANCES IN DESIGNING
ANTI-THROMBOTICS
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
Patient-driven. Innovative. Community. treat inflammation and infections and
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, which 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 $1,000
CBR Career Night
Jumpstart a postdoctoral fellow’s career with the $5,000
E D U CAT I O N
Postdoctoral Transition Award CBR Education Commitment
Support a clinical fellow in Translational Research Studies $75,000 • Support student research through
Make a CBR Symposium possible $25,000- competitive undergraduate, graduate,
$100,000 and postgraduate awards
Explore further: CBR.ubc.ca/support-us • Offer a range of stimulating educational
Edward M. Conway, MD, PhD symposia, workshops, and seminars
Director, Centre for Blood Research • Provide cutting-edge career
Tel: 604.822.4252 | Email: ed.conway@ubc.ca development opportunities for our
trainees
2
D
TABLE OF CONTENTS
PUBLISHED BY
Knowledge Translation Committee
Busting” Ability
Nico Werschler
Sarah Bowers
Sreeparna Vappala
Dr. Stefanie Mak*
Dr. Stefanie Novakowski
29 Canadian Blood
Tseday Tegegn
Wayne Zhao
* indicates Editorial Board member PROFILES Services Visit
Secret Lives of CBR
11
COVER PHOTO Macrophages in mouse
Researchers
adipose tissue after high-fat diet, by
Nooshin Safikhan
BLOG cbr.ubc.ca
FACEBOOK @cbrubc AWA R D S
TWITTER @CBR_UBC
15 CSI 2018
necessarily reflect the views of the centre
or the university.
OPINION
Address correspondence to:
CONTACT Recipients
30 GMOs
stefanie.mak@ubc.ca
Knowledge
Translation
Committee
28 Michael John Page
PDF Award
Science beyond academia
3
Research
4
Research
5
Research
6
Awards
7
Research
I f you, loved ones or friends suffer from diseases that may involve
abnormal blood clotting, such as heart attack, stroke, atherosclerosis,
deep vein thrombosis, pulmonary embolism or even cancer, commercials
due to the requirement of emergency surgery or to curtail bleeding side
effects.
on “blood thinners” (anticoagulants) may catch your attention more than So, what else do DOACs do in addition to inhibiting clot formation?
other drugs while watching your favourite TV show. Drug advertisements Before answering, let’s do a very brief review of how clot-formation and
are everywhere! They often promise us clinical benefits that outweigh side clot-busting happens in our blood vessels.
effects, even better outcome than “traditional” drugs used for decades to
mitigate the same condition/disease. Regardless of the length of clinical Maintaining the circulation of blood requires extensive molecular
use, drugs are continuously under investigation in a quest for a deeper surveillance orchestrated by many enzymes and cofactors. They help
understanding of their mechanism of action and novel applications. us form healthy clots to prevent us from bleeding and to rapidly
clear obstructive clots. These dynamic events are broadly classified as
A recent publication from the Pryzdial lab at the Centre for coagulation (clot-forming) and fibrinolysis (clot-busting). Clot-forming
Blood Research (CBR), took a deeper look at two relatively new clotting can be initiated through two mechanistic arms forming complexes called
factor Xa (FXa)-directed oral anticoagulants (DOACs) known as “extrinsic tenase” upon tissue injury to initiate FXa production and
rivaroxaban (Xarelto®) and apixaban (Eliquis®). You have likely seen their “intrinsic tenase” to amplify FXa production. Think of these events as two
advertisements over the past few years. Both were approved by the U.S. “waterfalls” merging together to create a big splash. In this case, FXa!
Food and Drug Administration in 2011 and 2012, respectively. This class
of anticoagulants is the first to be approved since the advent of warfarin Various coagulation factors including FXa play “double agent”
in 1954. Unlike warfarin, which simultaneously inhibits several clotting where they perform an additional task opposing their primary role.
factors including FXa, these DOACs function by specifically blocking When bound to an anionic phospholipid-containing membrane (e.g.
only the active site of FXa. This reduces the generation of thrombin (a key activated platelets), FXa is sequentially cleaved by plasmin (a key clot-
clot-forming enzyme) and thus prevents clot formation. DOACs are an busting protein) from its intact form, FXaα, to FXaβ and then to Xa33/13.
improvement over the traditionally administered warfarin because they Although, plasmin generation was enhanced in the presence of either
target only one clotting factor, requiring less frequent laboratory tests and FXaβ or Xa33/13, the former resulted in superior plasmin generation in
no dietary restrictions. Furthermore, in May 2018, an antidote named plasma.
andexanet alfa (andexanet) was approved if rapid reversal was required
8
Research
The Pryzdial lab previously showed that irreversible chemical modification of FXaβ reduced
the formation of Xa33/13 and promoted clot-busting. This observation lead to the hypothesis that
FXa-blocking DOACs enhance clot-busting ability by stabilizing FXaβ and inhibiting further
fragments.
Dr. Rolinda Carter, the lead author of “Rivaroxaban and Apixaban Induce Clotting Factor Xa
Fibrinolytic Activity”1 explains her work in this brief interview:
Knowledge Translation Committee (KT): What is the specific finding of your publication?
Dr. Rolinda Carter (RC): The study identified a new mechanism by which FXa-directed DOACs
can enhance clot dissolution.
KT: Does this finding affect our current clinical understanding of DOACs?
RC: It’s hard to really give clinical conclusions because a clinical study was not done. Nevertheless,
it would go back to the positive use of FXa-DOACs to treat deep vein thrombosis and thus prevent
post thrombotic syndrome which has links to ineffective clot dissolution.
KT: Are more factors acting as “double agents” in coagulation and fibrinolysis currently being
studied? Do you think our most common understanding of fibrinolysis and coagulation as
separate entities is coming to end?
RC: More and more researchers are finding that elements of the clotting cascade have multiple
functions. Studies are ongoing in the Pryzdial laboratory to look at the role clotting factor Va has
in clot-dissolution. Further investigation is also ongoing to optimize the clot-busting activity of
FXa derivatives.
KT: What was unexpected during your investigation? Did it deviate from the initial hypothesis?
RC: The initial hypothesis was that anticoagulants would bind to the active site of FXa, preventing the formation of Xa33/13 and thus enhance clot
lysis. This enhancement was not due to reduced thrombin generation and the consequent effects on its numerous functions, but its ability to bind to the
active site of FXa and promote plasmin generation. Thus, our findings were in line with the original hypothesis.
1
J Thromb Haemost. (2018) 16(11):2276-2288. C
9
Awards
O nce a year, the Centre for Blood Research provides travel awards to Postdoctoral Fellows and Research Associates to aid in
their travel to conferences and academic events. Any CBR Postdoctoral Fellow or Research Associate is eligible to apply,
provided they have not received an award within the last year. Each award offers up to $1,000 to supplement other funding sources.
Consistently throughout the years, recipients have attended, then presented their research at a diverse range of informative and
exhilarating conferences. Upon their return, awardees write short reports on the conferences they attended and their experiences.
These are posted on the CBR website.
Dr. Pierre-Marie Andrault, Brömme Lab Dr. Narges Hadjesfandiari, Devine Lab
Will attend the Atherosclerosis Gordon Will attend the AABB conference
Research Conference in Newry, Maine, on transfusion medicine & cellular
USA therapy in San Antonio, Texas, USA
Dr. Michael Hughes, McNagny Lab Dr. Amy Lee, Hancock Lab
Dr. Erika Siren, Kizhakkedathu Lab Dr. Hesham Soliman, Rossi Lab
10
Profiles
11
Profiles
12
Profiles
What are some of the research projects your lab is focused on now? What excites you the most about your work? What work are you most
I am involved in several projects including, for example, organ-on-a- proud of?
chip and cellular printing. We have a tumour-on-a-chip wherein we What’s most exciting about research in general is exploring things that
culture spheroids, which are models of tumours. We make them three- have not been solved before. In my lab, we are building technologies that
dimensional, so they actually model multi-cellular structures, and include enable scientists to do things they can’t do yet. Once we have achieved that,
not just cells found within the tumour, but also extracellular components, we would move forward to working with partners to make fundamental
like the proteins important for cell attachment. We use hydrogel beads to discoveries. It’s exciting to create these new technologies, and I’m very
grow the cells, and this allows us to study the effect of hypoxia on the cells proud of my trainees who have the perseverance and patience to stick
in a dynamic matter, as these conditions change over time in the body. through it. There are always lots of challenges, but they overcome them,
With microscopy, we study in real-time, what’s happening to the cells. and I am very proud of that.
We are also collaborating with colleagues at St. Paul’s Hospital to create
an airway-on-a-chip. There, we are modeling a very specific part of the If you had any advice for trainees, what would it be?
lung and studying the effects of fibrosis in chronic obstructive pulmonary Be open to investigating new things. One of my challenges that I did not
disease and asthma. foresee in the organ-on-a-chip project, was how difficult it would be to
image the cells. My students were not afraid to explore new microscopy
In terms of cellular printing, our work focuses on flow hydrodynamics techniques, regardless of what their academic background was. C
in inkjet printing. When you are printing cells, the cell diameter is very
close to the size scale of the inkjet nozzles. Our research was the first to
see what’s happening inside the nozzle, close to the cell, using high-speed
imaging. This lets us study how different properties of the ink affect the
cells during the printing process.
Is the focus of your lab on the biology or building the tools and models
for studying the biology?
Ideally, it’s both. We’re not just building bridges for other people, although
this really drives us in terms of what we build, because it would be
nonsensical to make something and tell other researchers it’s what they
need. The hypoxia study arose from conversations with researchers at
the BC Cancer Center, who knew it was important to study the hypoxic
conditions in a dynamic setting. This is what drove us to spend time Tumour-on-a-chip: Breast tumour cells growing and forming
developing this technology. To do this, I try to build a group of students multicellular spheroids, encapsulated within gel-like droplets.
who come in from different backgrounds and then complement each Individual cells are labelled in green (right). Image credit: Lab
other. That way we use the natural strengths of each trainee, depending Chip (2010) 10(18): 2424-32.
on their background; but there are still opportunities for them to work
together and learn from each other.
How do you think your research fits in with the CBR, in terms of their
overall goal and their ongoing projects?
While we’ve been making tumor models with our technology, we can
easily build different types of models with these tools that would be
relevant to other researchers at the CBR. For the inkjet project, in addition
to tissue engineering, we are trying to dispense single cells. If we are able
to rapidly dispense single cells in a high-throughput way, we can use
this for single cell studies, which should lead to additional collaborative
opportunities.
Chips used for co-culturing vascular lumen (left), co-culturing
spheroids (centre) and imaging co-cultured spheroids (right).
13
Profiles
A t the Centre for Blood Research (CBR), the holiday season was inaugurated
on December 7th, 2018. We all came together around the Christmas tree
to enjoy our annual holiday potluck and gift exchange. This kind of giving and
I began asking questions. The following day, I was able to pay a visit and observe
the children living there. I soon learned about their many needs, ranging from
medical needs, to educational support, to everyday items. Since then, I frequently
sharing is a form of “investment in others” that can yield big returns in our own ship packages to the organization and three years ago I traveled back to Isabela to
happiness and overall wellness, as described by Dr. Michael Norton of Harvard see how the children are doing.
Business School and Dr. Elizabeth Dunn of the Department of Psychology at
UBC in their book “Happy Money: The New Science of Smarter Spending.” What do you pack in the boxes?
CBR members are not new to the concept of “investing in others”; in fact I usually pack crayons, books, toys,
this is our year round tradition! We often carve out time to help one another meet used clothes, or anything else a kid
deadlines and simply raise each other’s spirits. The past few weeks, our “take-two might want/need. This is usually
initiative” further proved to us just how much our community values one another. achieved by finding good sales at
This initiative was organized by the CBR Health and Wellness Committee where different stores.
CBR members were provided with sweets that they can give to others as a form of
appreciation to those that go the extra mile for others. We went through a couple What are some challenges you are
of large bowls of assorted holiday sweets already! The Health and Wellness team currently facing to continue your
encourages our community to keep “investing in others” especially in this warm support to the orphanage?
season of giving and sharing. I am trying to find a better way to get
Our community also consists of many members who are involved in various the shipments out, because shipping
charitable organizations, whether local or far away. Among the extensive list of cost is the biggest hurdle of this process. A small box costs over $100 to ship and I
CBR do-gooders, Mr. James (Jim) Humphries from the custodial team is truly one ship about 6 to 7 boxes yearly!
to highlight. He is a firm believer in investing in others and he does this by giving
to the Sefton Village Children’s Home in Isabela, Philippines. Sefton Village was How has your life been enhanced by giving to this orphanage and other
established through the support of the Helga Mosey Memorial Trust as part of initiatives?
their charitable mission to help poverty-stricken children and young people. It has I really enjoy giving! In particular, when giving to the orphanage, I get a lot of
been a home and shelter for many, including abandoned newborns and children satisfaction when I see the children’s happy faces!
from abusive homes. The children can stay at the village or safely transition to
homes of loving adoptive parents. Have CBR members participated in your endeavours previously?
Throughout the year, they support me a lot by donating items to fill up boxes I
The Health and Wellness team recently interviewed Mr. Jim Humphries to place on the 4th floor by the women’s washroom in the west wing. When I initially
learn more about his charitable activities relating to Sefton Village. asked if the CBR would allow me to put a box there, the feedback I received from
Dr. Ed Conway was very positive and very encouraging for me to stay committed
How long have you been with UBC and to giving!
what do you enjoy about working at the __________________________________________________________
CBR?
I have been at UBC for 15 years. I like the As we head into the holiday season, the CBR Health and Wellness team
CBR because even though a lot of wonderful would like to thank Jim Humphries for the opportunity to learn about his giving
people come and go, it still feels like a family. endeavours. Also, we would like to recognize all our other do-gooders for their
contributions to our community and to the world in so many different ways. As
What prompted you to give, especially we transition into the New Year, may this season be time to prioritize our time
to the Sefton Village Children’s Home in and resources in a way that would maximize our health, wellness and happiness!
Isabela, Philippines?
I am motivated to give partly due to my Please consider donating to Jim’s box :) C
personality and upbringing. Growing up, I spent some time in an orphanage and
this experience allowed me to understand the needs of some of the children. The
reason I support the Sefton Village Children’s Home is accidental. Five years ago, I
visited the Philippines with my family, and one day, I noticed a rundown building.
14
Awards
T hanks to the Centre for Blood Research for providing me with the CBR
Postdoctoral Fellow Travel Award. Because of this travel award, I had
the opportunity to attend the 31st Annual Canadian Society for Immunology
can allow engraftment and delay xenorecognition by donor T-cells in an
immunocompromised host mouse. This prevention/delay in xenorecognition,
measured by the onset of T cell-mediated graft-versus-host disease (GVHD),
Meeting (CSI) for the first time. The meeting was held at Western University, may provide a longer window of opportunity for studying the immunological
located in London, the “forest city” of Ontario (and not England). The Western processes involved in human disease, thereby, generating a better-humanized
University campus is one of Canada’s oldest campuses, surrounded by beautiful mouse. I had several visitors interested in my work, as they had either struggled
gardens and trees, and has a mix of gothic and modern architecture. with humanized mice in their previous projects, were currently working with
At the event, I found the members of CSI to be exceptionally welcoming humanized mice, or were just curious if polymer-grafting was toxic to cells.
and accepting of newcomers like myself. These members celebrated contribu- In addition to getting useful feedback on my project, I had a great time
tions and accomplishments of all Canadian Immunologists. Investigators from networking, interacting and discussing novel ideas pursued by students and
UBC also made the list of accomplished immunologists. Dr. Michael Grant, a investigators. I was able to meet former lab members and to learn more about
professor at Memorial University and a former UBC student (B.Sc. and M.Sc.), their individual projects. Buffet lunches and dinners were held at the Great
received a CSI – Hardy Cinader Award; Dr. Megan K. Leving, a UBC professor, Hall, which also served as a venue to network and socialize. Meals at the Great
received a CSI Investigator Award; Dr. Martin J. Richer, an assistant professor Hall were accompanied by performances from Patrick Coppolino, a comedian;
at McGill University and a former UBC Ph.D. student received a CSI New In- Swagger, London’s favourite party band; and some hilarious ‘1-minute 1-slide’
vestigator Award. At the CSI symposium, there were interesting presentations voluntary presentations by trainees to increase attendance at their poster
on topics that included Aging & Immunosenescence: Susceptibility to Infection presentations. C
and Implications for Vaccination; Conventional and Unconventional T Cell
Development: Fate Choices & Spatial Factors; and Cancer Immunotherapy: Ba-
sic Mechanisms & Clinical Promise.
My poster, describing the making of a better-humanized mouse via
polymer-grafting, was one of 108 posters presented at the conference.
Humanized mice are an important tool in studying human diseases in an animal
model. My work demonstrated that the polymer-grafting of human leukocytes
15
Events
16
Events
The morning session started out with Dr. Alvin Schmaier (Case
Western Reserve University). He described how factor XII, a coagulation
factor in the intrinsic pathway, regulates inflammation by mediating a
neutrophil response. Next, Dr. Ed Pryzdial (Associate Director of the CBR
and a Canadian Blood Services Scientist) spoke of the extrinsic pathway,
describing how enveloped viruses contribute to clot formation and
infection through host-derived tissue factor and viral surface glycoprotein
C. Involving both the intrinsic and extrinsic pathways of coagulation, Dr.
Narcis Popescu (Oklahoma Medical Research Foundation) discussed
how disseminated intravascular coagulation develops during anthrax
infections, showing that Gram-positive peptidoglycan promotes tissue
factor expression by monocytes.
Switching gears, patient and clinician perspective talks on improving
comprehensive care for individuals living with sickle cell were given by
Storma McDonald, President of the Sickle Cell Association, and Dr. Hatoon
Ezzat, Director of BC Provincial Adult Hemoglobinopathy program. Sickle CBR Office Manager Hana Kim (left) with members of the Conway Lab
cell-associated pain was their key focus; they emphasized the importance
of pain management procedures to help guide physicians when patients
visit emergency rooms. Supported by various clinical success stories, Dr. platelets. Dr. Mark Looney (University of California, San Francisco), wound
Ezzat also noted the importance of treating with hydroxyurea to reduce up the day by wowing the audience with fluorescent images of live cells
pain and improve quality of life for these patients. moving about intact mouse lungs during experimental manipulations and
presented compelling evidence of the generation of new platelets in the
lung.
The formal part of the day came to a close with Dr. Stefanie Mak, the
CBR’s Education Program Manager, presenting awards to trainees for the
best posters ... some tough decisions, as there were many excellent ones.
Indeed, trainees were key participants in this event, delivering four of the
day’s talks, and presenting all of the posters. (For more information on the
trainee talks, see pages 18-19). Thanks were extended by Dr. Conway to
all of the speakers and organizers who helped make this year’s Earl Davie
Symposium once again, a fabulous educational and social experience.
Special thanks went to Stefanie Mak and Hana Kim (the CBR’s Office
Manager), our sponsors, and of course to Earl Davie, who annually “lends”
his name and support for this wonderful opportunity! C
Storma McDonald, President of Sickle Cell Association
17
Events
Parker Jobin (Overall Lab) presenting research talk Sreeparna Vappala (Kizhakkedathu Lab) shares
her work with an engaged attendee
Originally posted on the Canadian Blood Services R.E.D. blog on December 13,
2018.
“Three of the invited speakers today told me how special the trainees are
here at CBR. I had this on multiple occasions before! I think that CBR not
only has an excellent recruitment process in place, but we also offer very
Trainees at Earl W. Davie Symposium
good training programs.” - Dr. Ed Pryzdial, Canadian Blood Services scientist
and associate director of the CBR
18
Events
Trainee talks: from blood clotting to neuroinflammation Wayne is studying how temperature affects the quality and function
of platelets used for transfusion, which are currently stored at room
While the key proteins involved in blood clotting were identified temperature. There is growing interest in storing platelets in the cold, as
by Dr. Earl W. Davie and his colleagues over 40 years ago, many this may help improve their activity in patients with trauma and it may
questions remain, including questions about the role of coagulation allow an extension of the shelf-life of platelets, which is currently limited
factor XII (FXII) in regulating clotting. In the first trainee talk of the day, to 7 days. Wayne’s findings may help inform Canadian Blood Services
Tammy Truong (Weitz Laboratory, McMaster University), described and other blood operators as they explore new possibilities with platelet
her work characterizing the interaction between FXII and histidine-rich products.
glycoprotein, a protein found in plasma and platelets. This work could aid Platelets are also capable of mediating inflammation, and are known
in developing new treatments for blood clotting disorders, reducing the to bind to and internalize pathogens, including viruses. Tseday Tegegn
risk of bleeding associated with current drugs. Tammy was a recipient of (Pryzdial Laboratory) is following protein synthesis in platelets, with the
the CBR’s newly-established travel awards, made possible through the goal of understanding how platelet interactions with the Dengue virus
Sheldon Naiman and Linda Vickars Hematology Endowment Fund. alter proteins in the cell. She is investigating whether this contributes to
Most people attending a symposium on blood research would not low platelet levels (thrombocytopenia) during infection. Moving from
expect to hear about the impact of dietary fibre on their health; however, platelets to the immune system, Linda Yang (Scott Laboratory) is focused
this was not the case at this year’s Symposium. In an engaging talk, on adoptive cell immunotherapy, a promising potential treatment for
Hannah Robinson, (Osborne Laboratory, University of British Columbia), cancer. She is studying what the cells used in this therapy release and
described how high dietary levels of guar gum, a soluble fiber, provides deliver to cancer cells, to identify which specific components reduce
protection in animal models of multiple sclerosis, preventing entry of cancer cell growth.
immune cells into the nervous system. While guar gum can be found in Throughout the day, posters were judged by the CBR’s post-doctoral
ice cream, Hannah was quick to point out that “ice cream is not the cure fellows, research assistants, and investigators. This year’s winners were
for multiple sclerosis.” Emel Islamzada (3rd place), Tammy Truong (2nd place) and Stefanie
Occasionally, new roles can be found for well-characterized proteins. Novakowski (1st place).
In his talk, Parker Jobin, a MD/PhD student in Overall Laboratory Both Stefanie and Emel’s research demonstrate the roles of new
(University of British Columbia), described how tryptophanyl-tRNA technologies in blood research. Stefanie (Kastrup Laboratory, University
synthetase, a protein typically found within cells, can be released and alter of British Columbia) developed a method for delivering genetic material
cell growth in blood vessels, regulating inflammation. During the poster to platelets using nano-sized delivery systems, with the goal of creating
session, he shared how the Symposium has helped him in his professional modified platelets with improved activity during trauma or with extended
development: shelf-life. Emel (Ma Laboratory, University of British Columbia) studies
how red blood cells decrease in flexibility during storage using microfluidic
“At the Symposium, there’s a mix of both familiar and new faces. This devices, which allow single cells to be isolated and characterized. Her
provides an opportunity to hone your presentation skills with colleagues findings could potentially be used to identify ‘superdonors’, donors whose
you are comfortable with, while still meeting with many distinguished blood cells do not deteriorate during storage, leading to improved activity
researchers and clinicians.” - Parker Jobin, Overall Laboratory after transfusion.
From developing new drugs to learning how dietary fibre might
Poster presentations: the expanding realm of blood research impact our health, the 2018 Earl W. Davie Symposium was a diverse
and enlightening experience, and this based solely on the student
At the Symposium, each of the poster presenters have the opportunity presentations! The CBR symposia are always an invaluable learning
to practice their elevator pitches with 30-second ‘shotgun’ talks. Maria- experience for attendees, from trainees to patients to established
Elizabeth Beava (Jefferies Laboratory, University of British Columbia) researchers, and this year was no different.
gave a particularly enthusiastic talk that highlighted how the field of blood The Centre for Blood Research at the University of British Columbia
research has grown since the early focus on blood clotting proteins, as hosts three Canadian Blood Services scientists, and affiliated staff,
her work focuses on possible links between eye disease and Alzheimer’s postdoctoral fellows and students. Canadian Blood Services and the
Disease. The Symposium offers both trainees and researchers a chance to Centre for Innovation are proud to partner with the Centre for Blood
learn about research outside of their area of study, an opportunity many Research to deliver training and education events including the annual
trainees value. Earl W. Davie Symposium. C
“At the Symposium, you can meet patients, scientists and doctors. I
had the opportunity to talk to a trauma surgeon today, which gave me
a new perspective on my research. This Symposium is a great event that
provides wonderful opportunities for students!” - Wayne Zhao, Devine
Laboratory
19
Awards
20
Events
21
Opinion
22
Opinion
R PE65-mediated inherited retinal dystrophy leads to severe deterioration of vision and complete blindness in early adulthood1.
A small subgroup of patients, approximately 1000 people in the United States2, have mutations in both paternal and maternal
copies of the RPE65 gene that encodes retinoid isomerohydrolase, an enzyme involved in generation of the chromophore, 11-cis
retinal. This biallelic mutation has a very poor prognosis and is considered the most severe of inherited retinal dystrophies.
At the beginning of 2018, Luxturna, developed by Spark therapeutics, was approved by the Food and Drug Administration
(FDA) for treatment of RPE65-mediated inherited retinal dystrophy2. Luxturna is the first targeted gene therapy approved in the US,
representing a huge milestone in medical care. Through injection under the retina of each eye, adeno-associated virus introduces
a functional copy of RPE65. This allows the eye to regenerate the 11-cis retinal chromophore that is required for normal vision2.
Follow-up of participants in the Phase III trial showed that 27 of 29 patients regained their vision over the first year after treatment;
21 were able to complete an obstacle course in low light3. An article about 13-year-old Jack Hogan, the first patient to receive
Luxturna after FDA approval, can be read on Vox4.
But, with the increasing cost of bringing a therapeutic from the laboratory to FDA approval (approaching $1-2 billion USD5)
and with Luxturna only offering treatment to a small proportion of retinal dystrophies, how much does a single treatment cost?
Treatment of both eyes costs $850,000 USD ($1.1 million CAD), not including the cost of travel/secondary treatment/hospital care!
Does this hefty price tag spell disaster for Luxturna as it did for the first gene therapy agent from UniQure, Glybera? Glybera was
licensed in Europe in 2012 for treatment of lipoprotein lipase deficiency, an extremely rare condition. However, at a cost of over a
million USD, Glybera was purchased only once, FDA approval was not sought and Glybera met its demise in the pharmaceutical
market6.
To encourage sales of Luxturna, Spark therapeutics is offering rebates for patients who do not respond within a reasonable
time post-treatment7. The company is also working closely with insurance providers to reduce costs and allow the patients to pay
for the treatment in instalments. However, a million dollars paid through instalments could still take a lifetime to pay off. The high
price tag of these first two gene therapy treatments is worrying — if too few patients can afford Luxturna, will a domino effect ensue,
blocking further advancements in development of other gene therapies? Hopefully, the benefits of Luxturna will inspire a wave of
novel therapies for other genetic disorders. Spark therapeutics, in collaboration with Pfizer pharmaceuticals, is already expanding
Phase I and II trials of a second gene therapy for treatment of the inherited bleeding disorder, Hemophilia B8.
1
N Engl J Med (2015) 372(20): 1887-1897.
2
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm589467.htm
3
The Lancet (2017) 390(10097): 849-860.
4
https://www.vox.com/2018/3/22/17147312/luxturna-gene-therapy-retinal-disease
4
http://blogs.sciencemag.org/pipeline/archives/2017/10/18/drug-development-costs-revisited
5
https://www.technologyreview.com/s/601165/the-worlds-most-expensive-medicine-is-a-bust/amp/
6
http://ir.sparktx.com/news-releases/news-release-details/spark-therapeutics-announces-first-their-kind-programs-improve
7
https://www.pfizer.com/news/press-release/press-release-detail/spark_therapeutics_and_pfizer_amend_license_agreement_for_
investigational_spk_9001_in_hemophilia_b C
23
Events
W hile the eyes of the world were turned to the stars competing at
the World Cup 2018 in Russia, the CBR soccer team Blood Soccer
took to the field in the Graduate Student Society (GSS) Summer soccer
In the end, Blood Soccer’s field management gave them the 5-2 victory.
Blood Soccer was in the playoffs and beat MLS FC 7-4 before facing
Losers in the semi-finals. Keen to prove a point and not be intimidated
league. Having improved from 4th to 3rd place in the last two seasons, the by the Losers’ antics of the previous game, Blood Soccer came out all-
team was eager to keep the upward trend going. guns-blazing with hat tricks from Loïc and Nico. Blood Soccer tucked
Right from the start, despite most players not having played in a the Losers to sleep with a crushing 9-2 victory to reach the final for the
while, Blood Soccer hit its stride with a comfortable 5-1 victory against first time since the team’s inaugural season. The final matchup would be
Morphine in their opening game. Led by returning captain Prashant, there tough: Blood Soccer was facing Random Walkers. Though tied for points
seemed to be good chemistry between the new players and the veteran at the top of the standings, Random Walkers had almost double the goal
core of the team. However, there was still room for improvement and the differential and had handed Blood Soccer its only defeat of the season.
team would undoubtedly get stronger in the coming weeks as the players The final started as most do, both teams closely matched and
got more playing time together. neither wanting to make mistakes. Midway through the first half, Random
The second game offered more suspense as Blood Soccer and Walkers drew first blood. Not wanting to be down at half, Blood Soccer
Antiballies were closely matched. In the end, the difference was the managed to equalize shortly after and both teams entered the break
combination play between new recruit Loïc and veteran Abhinav which locked at 1-1. The players regrouped at halftime and Prashant made some
led to an Abhinav hat trick and, in total, accounted for 3 assists and all tactical changes that allowed Blood Soccer more freedom in the attacking
5 goals. This handed Blood Soccer their second straight victory as they third of the field. Right from the start of the second half the changes made
defeated Antiballies 5-3 before heading into a break. an impact as a nice passing sequence ended with Loïc getting brought
The winning streak was cut short in the next game as Blood Soccer down inside the box. No need for VAR — it was definitely a penalty. Blood
suffered its first defeat of the season (2-5) to Random Walkers. Blood Soccer took the lead as the penalty was coolly taken. From there, the flood
Soccer was missing a few players and, despite the rest and practice, gates opened. A deflected shot found the back of the net before two more
couldn’t match Random Walkers’ play. goals were added on by Blood Soccer for a 5-1 lead. Random Walkers did
This loss meant Blood Soccer had to win their next game against have chances, even hitting the crossbar a couple times, but were unable
Losers to clinch the top seed in their bracket. From the start, the game to answer. Even up 5-1, team captain Prashant was anxious and could be
was tense, and the Losers were getting frustrated by the tactical play of heard every 2 minutes yelling “REF, HOW MUCH TIME LEFT?!?”.
Blood Soccer blocking the midfield and forcing long balls over the top At last, the final whistle came and Blood Soccer had won! For the
(inevitably intercepted by Blood Soccer’s clutch defenseman Charles). first time, they had gone all the way and were champions. The cup was
In the second half, after a tackle from behind that wasn’t called by the presented to Prashant and, all together, the squad celebrated as they
referee, the game’s physical play was ramped up culminating in a red card hoisted the trophy. With this year’s success, the expectations will be high
for the Losers centre-back and a heated argument between the two sides. for the champions when they return to defend their title next year. C
24
Awards
2018: Celebrating 50 mized method for the proteomic analysis of bone. This attracted interest
from a number of researchers keen to learn from our developments in tis-
Years of FECTS
sue extraction, which remains a challenge for complete analysis of other
connective tissues such as cartilage.
It was a real highlight to see my former PhD advisory committee-
member, Prof. Ray Boot-Handford, deliver the Fell Muir Award plenary
lecture, where he described his scientific journey from the mapping of
the gene encoding type X collagen, through to ongoing clinical trials to
treat MCDS (a form of skeletal dysplasia caused by COL10A1 mutations).
This, combined with the discussions and new connections that I formed
By DR. PETER BELL, with other researchers, will be my enduring memory of a productive
Postdoctoral Fellow, Overall Lab conference. C
25
Opinion
W hen I started graduate school at UBC in 2012, I thought I was prepared. I had excellent marks, publications from research done as an
undergraduate student, and even an NSERC award. Three years later, I was in therapy and seriously considering quitting grad school. I
was drained, anxious, unable to focus, and struggling with tasks that I had previously found easy. I felt broken. What went wrong?
I was used to working in a linear undergraduate environment. New classes each term, with a scheduled set of tests and assignments.
Expectations were clear. It was easy to prioritize tasks based on how close the due date was and what percent of the mark the assignment
made up. Feedback came regularly. While some classes were easier than others, there was usually a correlation between how much effort I
made and my mark. In contrast, after the first two years of graduate school and my comprehensive exam, I had just one big multi-year project
looming in the distance: my thesis. Deadlines were vague. Most frustratingly, the amount of time and effort I put into my experiments did not
guarantee good results.
In the three years since then, I’ve picked up a few principles that have helped me to move forward – things I wished I had taken heed of
sooner. Maybe they can help you, or someone you care about.
I’m not out of the tunnel yet, but I see an end, and a light.
1. Prioritize taking care of yourself. We all know that it’s important to eat properly, get 7-8 hours of sleep, and exercise. Yet it is very easy to let
these things slide when you feel pressure to get research results. You can’t always control your research schedule, but remember that you
can’t do your best work when you’re not at your best - too much overtime can decrease your productivity.
2. Get outdoors. Spending time in nature can reduce stress, depression, and anxiety. Walking can increase creativity, especially walking outdoors.
If you’re feeling stuck, try a walk in the UBC Botanical Garden or Nitobe Memorial Garden (your UBC card gets you in for free).
3. Stay connected. We are not meant to be alone, and yet, many of us withdraw when we are most in need of help. It makes a huge difference to
be around people who care about you, or those who may have similar struggles. Find those people. Find them in the lab, in your department,
in the CBR, in UBC clubs, in the wider community. Talk to them.
4. Have a personal side project. When things are going poorly in the lab – and they will, at some point or another – it really helps to have something
else going on in your life that you can feel good about. Volunteering, athletic activities, and creative projects are good places to start. This
can also be a good way to make those social connections or get outdoors – and develop skills in teamwork, communication, or leadership.
5. Turn on the music. I swear, there are days when the only thing that keeps me going is singing along with Sarah Slean in the tissue culture room.
6. Ask for help early and often. You’re not expected to come to grad school with all the skills necessary to write a thesis. If you feel stuck, talk to
colleagues in your lab, your supervisor, or your committee members. Above all, if things aren’t going well, don’t cancel meetings with your
supervisor! You may want to wait until you have better results, but your supervisor is supposed to help you figure out how to get those results.
7. Think about how you work. Odds are good that you, like me, have work habits that worked great in undergrad but might not be well suited for
grad school. Now’s a good time to reassess! I’m still working on this myself, but taking time to prioritize tasks and think about how they fit
into a thesis is more effective than just trying to power through an overly cluttered to-do list.
If you are having a hard time and don’t know who to talk to, try the resource list on the CBR website or someone on the CBR Mental Health
Contacts list. C
26
Events
Blood is Bonding
By DR. GEORGINA BUTLER, Research Associate, Overall Lab
F ebruary is “The Month of Love” and CBR’s Overall lab took the opportunity
for an alternative lab bonding experience. Canadian Blood Services Research
Centre for Innovation netCAD Blood4Research Facility needed 500 donations
for evaluation of new whole blood collection packs. Instead of bowling or pub
night, we booked a slot at netCAD for a group blood donation. For many of us
from countries ineligible to donate in the regular system, it was our first blood
donation. We enjoyed the guilt-free eating of sweet and salty snacks, and even
had a competition which was won by Marli – who filled her bag with 488 mL
in just 4 minutes, 28 seconds! We bumped into Dr. Stefanie Novakowski, an
alumna of the Kastrup lab who said, “I used blood throughout my 5 year PhD, so
I’m here to give back.” Why not consider a visit to netCAD for your next team-
building event?
Awards
T he Canadian Institutes for Health Research (CIHR) Project Grant competition takes place twice a year for the purpose of supporting Canadian
researchers’ innovative ideas that will advance health-related knowledge, health research, health care, health systems and/or health outcomes.
This funding assists incremental, innovative knowledge translation projects from discovery to application, including commercialization. To be eligible,
the nominated principal applicant must be either an independent researcher or a knowledge user. This grant ranges between $50,000 and $990,000
per year for the grant durations of 1 to 5 years.
27
Awards
Left to right: Dr. Rachel Fernandez; Dr. Aly Karsan; Dr. Jennifer Grants; Dr. Ross
MacGillivray; Mr. Roger Page; Ms. Hourik Khanlian.
O n Wednesday October 17th, Dr. Jennifer Grants was presented with the 2018 Michael John Page
Postdoctoral Fellow Award by the Department of Biochemistry & Molecular Biology (BMB) and
the Centre for Blood Research (CBR). This award was developed by BMB and CBR in memory of Dr.
Page who received his Ph.D. from UBC in 2004. After postdoctoral work in St. Louis, Dr. Page was a
faculty member at the University of California, San Francisco before dying suddenly in 2013 at age 36.
Dr. Grants’ presentation was attended by Mr. Roger Page (Michael’s father who flew in from Thunder
Bay), Dr. Leonard Foster (Head, BMB), Dr. Ed Pryzdial (Associate Director, CBR), Dr. Aly Karsan
(Professor of Pathology & Laboratory Medicine; Dr. Grants’ postdoctoral supervisor and a member
of the CBR) as well as Dr. Rachel Fernandez (Associate Dean, Postdoctoral Fellows Office & Student
Professional Development) and Ms. Hourik Khanlian (Manager, Human Resources and Postdoctoral
Affairs) from the UBC Faculty of Graduate + Postdoctoral Studies.
Reflecting Dr. Page’s attitude to life, the Michael John Page Postdoctoral Fellow Award recognizes
academic excellence as well as extracurricular activities. The Award is funded through an endowment
set up by the Page Family in addition to contributions from BMB and CBR. Dr. Grants presented a
very clear summary of her research starting as an undergraduate at the University of Victoria, her
graduate work under Dr. Stefan Taubert’s supervision at the Centre for Molecular Medicine and
Therapeutics and her current studies with Dr. Karsan at the BC Cancer Agency. Dr. Grants has studied
transcriptional regulation in various model systems including blood cells. She presented evidence
linking inflammation, ageing and myeloid malignancy using transgenic mouse models for specific blood
cancers. Following her scientific presentation, Dr. Grants explained the important role of music in her
life including her training in piano, violin and voice. She capped off an entertaining seminar by playing
Edward Elgar’s Salut d’Amour on her violin. Following her presentation, Mr. Roger Page presented Dr.
Grants with the 2018 Michael John Page Award (a memorial plaque plus a $3,000 prize). A splendid
time was had by all! C
28
Events
29
Opinion
Social Uncertainty?
may cause significant ripple effects impacting the health of
consumers or the surrounding environment. For example, if corn
is engineered to produce a natural insecticide, what will happen
to that insecticide? Could it harm people eating the corn, or start
an evolutionary arms race with pests? For decades, scientists,
consumers, and regulators have attempted to assess and respond
to these risks.
30
Opinion
of the new herbicide compared to alternative herbicides used in Despite these problems, it is important to recognize that
a given country6. Ecologists express more uncertainty regarding GMOs do have a wide range of potential benefits6. Plants that are
the safety of GMOs than researchers studying other issues such higher yielding, more nutritious, and more resistant to changing
as food safety, where the scientific debate is not so much about conditions could be vital in addressing food security in the face
whether GMOs are dangerous, as it is about how confident we are of climate change. Replacing pesticide use with naturally pest-
that GMOs are safe5. resistant crops could have environmental benefits if properly
managed. These rewards are perhaps too significant to leave on
The consumer perspective is more skeptical of GMOs than the table, but our current system of relying on private corporations
the general scientific community. This skepticism may partly be to bring GMOs to market has not furthered the best usage of this
due to a fuzzy understanding of the technology, or viewing DNA technology. Additional studies would improve our understanding
as an ‘essence’ of living organisms that shouldn’t be tinkered with7. of the long-term effects of GMOs in biological and ecological
However, consumer distrust is not just targeted at the technology systems. However, it is essential that we address the human
behind GMOs, but also at the corporations that seek to profit from systems of food production in order to realize public benefits while
them. GMO patents – and Monsanto’s aggressive defense of these managing public risks.
patents – have resulted in unprecedented corporate ownership of
living organisms. Many consumers are concerned about how well 1
http://www.pewinternet.org/2015/01/29/public-and-scientists-views-on-
we can trust the giants that produce our food – GMO or otherwise science-and-society/
– and the institutions that regulate it. 2
J Agric Food Chem. (2013) 61(48): 11695–701.
3
J Anim Sci. (2014) 92(10): 4255–78.
Multiple government institutions have responded to public 4
Crit Rev Biotechnol (2014) 34(1): 77-88.
discomfort with GMOs by requiring stringent safety assessments 5
Environ Sci Eur. (2015) 27: 4.
for each new organism. In theory, this is a reasonable response 6
J Econ Perspect. (2014) 28(1): 99–120.
to the varied possible characteristics of GM crops. In practice, 7
Trends Plant Sci. (2015) 20(7): 414–8.
however, only crops backed by a strong commercial interest can 8
Science (2008) 320(5875): 468–71. C
make it over costly regulation hurdles while crops with primarily
humanitarian benefits struggle to fund the necessary safety trials.
For example, Vitamin A-enriched ‘Golden Rice’ was predicted to
save millions of lives by reducing vitamin A deficiency in Africa and
Asia but has yet to make it to market8. This imbalance perpetuates
the public perception that GMO development is dominated by
large corporations and unlikely to provide significant public benefit.
This belief promotes continued opposition to GMOs, further
undermining the ability of this technology to benefit society.
31
We thank all our donors from academia, industry, and
the private sector for your generous contributions. cbr.ubc.ca