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FIXING

DAMAGED
NOVEMBER 2016 BLOOD VESSELS
EVENT GLANCES
NEW CLOT
BUSTING DRUG

PLUS
CBR MEMBERS
RECEIVE
PRESTIGIOUS
AWARDS

DROP THE KNIFE


NEW TARGET
FOR IBD
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
promote wound repair
Patient-driven. Innovative. Community.
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:

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 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
Make a CBR Symposium possible $25,000- • Offer a range of stimulating educational
$100,000 symposia, workshops and seminars
Explore further: CBR.ubc.ca/support-us • Provide cutting-edge career
Edward M. Conway, MD, PhD development opportunities for our
Director, Centre for Blood Research trainees
Tel: 604.822.4252 | Email: ed.conway@ubc.ca

2
PUBLISHED BY
Knowledge Translation Committee
EDITOR-IN-CHIEF  Anna Sinova
DESIGNER  Amarpreet Grewal
CONTRIBUTING EDITORS
Abhinav Ajaykumar RESEARCH PEOPLE
Andrew Alexander

4 7 Dr. Kizhakkedathu
Georgina Butler
Diana Canals Therapeutic target
Rolinda Carter
Deb Chen for IBD Promoted
Jenny Chik

6 25 Interview
Tara Fernandez
Amarpreet Grewal Stable with
Anthony Hsieh
Jenny Huang Blood Clot Dr. MacGillivray
Michel Hughes
Prashant Kumar

8 New Clot
26 Father of Modern
Victor Lei
Bryan Lin
Houra Loghmani-Khouzani
Ido Refaeli
Dissolving Drug Hematology
Sara Saberi

10 Immuno- 27 Tribute
Erika Siren
Solmaz Sobhanifar to
Shawna Stanwood
Olga Zamudio
camouflage Dr. Sheldon Naiman
BLOG cbr.ubc.ca
FACEBOOK /cbrubc
TWITTER @CBR_UBC
INSTAGRAM @CBR_UBC

CBR magazine is published by the


11 Platelet
Safety AWA R D S
Knowledge Translation Committee,
which is a group of CBR graduate
students, postdoctoral fellows, and
research associates, who are interested
in science writing, blogging and mixed
12 Clearing
Overload
Iron
5 CIHR
Grants
media communications. It is distributed

13 Beta- 9 Student
free of charge to CBR and UBC alumni,
friends, and the scientific community.
Opinions expressed in the magazine do
not necessarily reflect the views of the thalassemia Awardees
centre or the university.
Address correspondence to:
The Centre for Blood Research
4th Floor, Life Sciences Centre
2350 Health Sciences Mall
Vancouver, BC, Canada V6T 1Z3
14 Fighting
Obesity OPINION
The KT Committee publishes
weekly at CBR News (cbr.ubc.ca) and
covers a wide range of topics: from
recent research highlights and opinion
pieces on science and academia, to
15 Host Defence
Peptides 23 High-school
Mentorship
event coverage and CBR initiatives.

24 ACS Chemistry
If you are interested in participating
in the KT Committee, email Anna at:
anna.sinova@ubc.ca or talk to one of
the members! All CBR members are MAJOR EVENTS
Championship
welcome to join.

Knowledge
Translation
16 Research
Day PROGRAMS
Committee

18 World 22 Health
Science beyond academia
&
CONTACT Thrombosis Day Wellness
anna.sinova@ubc.ca

Cover image credit: Heather Amos, UBC


20 Careers
Symposium
3
research Microscopy image. Photo
credit: Bernard Lo.

Drop the Knife!


MICHAEL HUGHES, R E S E A R C H A S S O C I AT E

The incidence of Crohn’s disease (CD) and ulcerative colitis (UC) (collectively known as inflammatory
bowel disease (IBD)) in Canada is among the highest in the world. Most troubling, the number of children in
Canada with IBD has doubled in the last 20 years. A confluence of environmental factors, such as city dwelling
in industrialized Western nations, may be at least partly to blame for this rapid rise in IBD.
IBD is a life-long, chronic inflammatory disease that can be severely debilitating if not controlled.
Frequent bouts of inflammation cause permanent scarring (fibrosis), which can interfere with nutrient
absorption and excretion functions of the intestine. Currently, surgery is the only way to remove scarred tissue.
Consequently, approximately 70% of patients with CD and 30% with UC will require surgery at least once
in their lifetime. Removing scar tissue in the gut is not a trivial surgery; considerable tracts of large bowel are
usually removed, as well as sections of the ileum (critical for nutrient absorption). Going under the knife for a
patient with IBD frequently necessitates a drastic change in lifestyle.
Bernard Lo, a PhD candidate in the research group led by CBR Principal Investigator Kelly McNagny,
discovered a novel cellular pathway that promotes intestinal fibrosis in a CD-like mouse model. His findings
highlight a therapeutic target for the development of drugs that may block fibrotic processes and reduce the
need for surgery in patients with IBD.
In his work, recently published in September’s issue of Science Immunology, Bernard used a Salmonella-
induced mouse model of gut fibrosis that shares many of the pathological features of human CD, to
demonstrate that group 3 innate lymphoid cells (ILC3s) are required for intestinal fibrosis.
He also found that a transcription factor, retinoic acid receptor-related orphan receptor-alpha (RORα),
controls the function of these lymphoid cells in the gut. As the gene name suggests, the ligand of RORα has
not been formally identified. However, potent small-molecule synthetic antagonists and agonists are known,
making RORα a viable therapeutic target for new drugs that can block fibrotic mechanisms in CD.
Bernard’s next step is to demonstrate the ability of existing RORα-antagonists in vivo to block the fibrotic
process. Success of the next generation candidate drugs will hopefully spare patients with IBD from going
under the knife!
Science Immunology, 1(3)C

4
awards

CIHR Foundation and Project Grants Recipients


A M A R P R E E T G R E WA L

The Canadian Institutes of Health Research restructured their spending strategy in 2015. The agency has replaced the 12 large and
small funding awards to two funding streams: the CIHR Project Grant and the CIHR Foundation Grant.
The Foundation Grant supports research leaders from all career stages to build and conduct programs of health research across
CIHR’s mandate. As the name suggests, the Foundation Grant is designed to provide long-term support for health researcher leaders. The
majority of grants range between $50,000 and $1.5 million per year over 5 to 7 years depending on the researcher’s seniority and history.
The Project Grant is designed to capture ideas that will contribute to the creation and use of health-related knowledge. It supports
a variety of health-related research and knowledge translation projects from discovery to application, including commercialization. This
grant ranges between $50,000 and $750,000 per year for the grant durations of 1 to 5 years.

Congratulations to the two CBR members who have received Congratulations to the four CBR members who received the
the CIHR Foundation Grant: CIHR Project Grants:

Dr. Robert Hancock:


Dr. Christian Kastrup:
“The network biology of stem cell
“Materials and Mechanisms for
derived macrophages: Deciphering
Understanding and Controlling
the role of cellular reprogramming in
Hemorrhage”
sepsis”

Dr. Christopher Overall:


Dr. Wilfred Jefferies:
“From Proteolytic Networks to
“Studies on novel immune-surveillance
Human Biology and Disease: Protease
mechanisms underlying cancer
regulation of signal transduction in
elimination”
chronic inflammatory diseases”

Dr. Jayachandhran Kizhakkedathu:


“Novel One-step Approach to a
Universal Anti-adhesion Coating to
Prevent Catheter-associated Urinary
Tract Infections”

Dr. Kelly McNagny:


“Innate Lymphoid cells and RAR-related
orphan receptor alpha (RORa) as
therapeutic targets for gastrointestinal
fibrosis and Crohn’s disease” C

5
Photo credit: Kastrup Lab - MSL
research

Christian Kastrup’s Team Leads the Way


Towards a More Stable Blood Clot
ROLINDA CARTER, P H D C A N D I D AT E

Effectively sealing a damaged blood vessel is the key to stopping the coagulation cascade has been shown to increase clot adhesion when
bleeding. Physiologically, this is achieved by an initial platelet plug copolymerized with endogenous components during clotting.
followed by a more stable fibrin rich blood clot. Fibrin, which is formed When asked about the expected impact of their research, Karen
from fibrinogen, is the molecular mesh of the clot. It is stabilized and answered, “We believe that strategies for artificially enhancing blood clot
attached to the site of vessel injury by clotting factor XIIIa (FXIIIa) adhesion may lead to the development of novel hemostatic agents that
through irreversible crosslinking. When physiological adhesives are can mitigate bleeding under coagulopathic conditions in which fibrin
depleted, fibrinogen replacement therapy is used to stop bleeding. This may be depleted or degraded. We are currently exploring modifications
strategy, however, is not fail-safe from re-bleeding due to normal fibrin to the Q-PEG material and its formulation and hope to take this towards
clot dissolution. Thus, alternative mechanisms to increase clot adhesion new therapies for trauma-induced coagulopathy (TIC)”. In TIC, patients
are needed. often develop fibrinogen deficiency and are more prone to enhanced
Karen Chan, a PhD candidate in the Kastrup lab at the CBR, fibrinolytic activity.
along with other scientists, saw a promising alternative therapeutic in
the use of FXIIIa-crosslinkable synthetic polymers such as Q-PEG.
Q-PEG is a previously characterized 8-armed polyethylene glycol that
is conjugated to a glutamine-containing peptide derived from α2-
antiplasmin. In a recently published Biomacromolecules article, Karen
and team demonstrated that Q-PEG can be formulated with spermidine,
a polyamine substrate enabling crosslink formation by FXIIIa. This
changes clot properties when added to blood, and the combination
was shown to increase the adhesive strength of endogenous clots,
restore the adhesion of fibrin poor clots and increase the resistance
Karen Chan
of clots to dissolution in the presence of the serine protease, tissue
plasminogen activator. This is the first time that a material exogenous to Biomacromolecules, 17(6): 2248-2252C

6
In vivo endothelial cells lining blood vessels. people
Photo Credit: Piyushkumar Kapopora

Dr. Jay N Kizhakkedathu


appointed to Full Professor!
A M A R P R E E T G R E WA L

Congratulations to Dr. Jay N Kizhakkedathu for his promotion system. In 2011, after a rigorous process of evaluation of his many
to a Full Professor of Medicine in the Department of Pathology and accomplishments, he was promoted to an Associate Professor.
Laboratory Medicine. Now, Dr. Jay N Kizhakkedathu has been appointed to the rank
Dr. Kizhakkedathu’s remarkable achievements started early of Full Professor by the Senior Appointments Committee and the
in his career; in the all-India entrance exam for higher degree UBC President. The process of being promoted to Professor is not
positions in science and engineering, he ranked in the top 20 of automatic nor is it based on years of service. Being appointed to the
the many thousands of applicants. There, he completed his PhD rank of a Professor is reserved for those whose contributions are
studies with a group well-known for polymer research, and in 1999, considered outstanding in teaching, scholarly activity and service
UBC was fortunate to recruit him as a post-doctoral fellow to Dr. to the community and university. They have met the standards
Don Brook’s laboratory. It didn’t take long for Dr. Kizhakkedathu to of excellence and have attained distinction in their discipline. In
demonstrate his skills, as he has rapidly devised solutions for long- addition, they have achieved excellence in teaching and educational
standing problems in biomaterial compatibility, and along the way, leadership roles.
created several new technologies for clinical use in the fields of Dr. Kizhakkedathu’s research is focused on understanding
hemostasis-thrombosis, vascular biology and nephrology, to name molecular interactions of synthetic polymers with biological
just a few. systems in order to design novel biomaterials. He takes an
In 2005, Dr. Kizhakkedathu was appointed to be an Assistant interdisciplinary approach by integrating polymer synthesis with
Professor after obtaining the CIHR New Investigator Award for well-designed biological assays and animal models to create novel
his work on developing universal red blood cells by modifying polymers and technologies to address unmet clinical needs. His
their chemical structure. This led to his work on hPG, which recent publication on heparin reversal has received international
serves to effectively mask antigens on the red blood cell surface, media attention: UBC News, Chemical and Engineering News, Red
thereby creating cells that could escape detection by the immune Orbit, News Everyday, and other news sources. C

7
research Scanning micrograph of of human blood clot.
Photo credit: Manu Thomas Kalathottukaren

The Pryzdial Lab Advances a Novel


Clot-Dissolving Drug
ROLINDA CARTER, P H D C A N D I D AT E

therapeutic to replace tPA have been unsuccessful.


By thinking “out of the box”, the Pryzdial lab at the Centre for Blood Research
previously showed that clotting factor Xa (FXa) is modified by plasmin-cleavage to
acquire clot-dissolving properties. This was the first time that FXa was shown to have
this schitzophrenic role in controlling blood flow. Capitalizing on this finding, in the
latest Journal of Thrombosis and Haemostasis publication, Dr. Pryzdial and team
collaborated with Dr. William Sheffield at McMaster University to generate and test a
chemically modified form of FXa called Xai-K. This new form of FXa was designed to
stabilize C-terminal lysine exposure, which facilitates the assembly of tPA and its substrate
plasminogen, and thus increase generation of plasmin. Since Xai-K has to be associated
to the clot or pro-coagulant surfaces to exhibit this function, localized instead of systemic
plasmin generation is achieved.
Through a number of in vitro and in vivo experiments, the authors found that Xai-K
was not only able to dissolve clots at a faster rate than tPA-based therapeutics (Alteplase and
Tenectaplase), but it also functions as a blood thinner through competition with normal
Dr. Ed Pryzdial FXa. Hence, an alternative to the current treatment used has been identified.
“It was amazing to see how fast clots cleared when Xai-K was given to a mouse
Heart attack and stroke are leading causes
compared to today’s most common therapeutic” – commented Scott Meixner, the research
of death worldwide and are due to excess clot
assistant in the Pryzdial lab who generates and characterizes Xai-K.
blocking the normal flow of blood. To treat
In addition to using Xai-K alone, the team also showed that Xai-K could be
these clots, tissue plasminogen activator (tPA),
administered in combination with a 34-fold lower dose of the tPA analogue, Tenectaplase,
the key physiological enzyme that initiates clot
to restore blood flow. The latter is a substantial finding as decreasing the dose of tPA will
dissolution, was developed into a therapeutic
ultimately decrease the bleeding risk in patients and still enable clearance of highly resistant
drug and is co-administered with a blood thinner.
clots.
The ultimate purpose of tPA is to generate
“Two decades of major clinical trials aimed at improving the safety of clot-dissolving
plasmin, the enzyme directly responsible for
drugs have been disappointing. Xai-K marks a new strategy to dissolve clots based on a
breaking down the clot. While having saved many
novel biochemical pathway our lab discovered. We’re excited that its preclinical safety and
lives, the use of tPA in the clinic is complicated
efficacy profiles suggest promising advances are finally on their way” – said Dr. Ed Pryzdial,
by side-effects including an increased risk of
the principal investigator and first author of the paper. Further studies are currently in
bleeding due to systemic plasmin generation
progress as the lab seeks to take this technology away from the bench and closer to the
and re-appearance of abnormal clots. To date,
bedside. C
advances at finding a safer and more effective

8
awards

CBR Members Receive Prestigious


Awards
A M A R P R E E T G R E WA L

Dr. Natalie Zeytuni, a post- J. Andrew Alexander, a PhD Dr. Dustin King, recently
doctoral fellow in Natalie Student in Natalie Strynadka’s obtained his PhD from Dr.
Strynadka’s lab, has received laboratory, gained a Doctoral Strynadka’s laboratory, for which
a Banting Postdoctoral Research Award in a priority he received the 2016 Governor
Fellowship to support her work area of Infection and Immunity General’s Gold Medal. Now
on on structural and biochemical for his work entitled ‘Trouncing he is a postdoctoral fellow
analysis of the Type VII secretion the superbug: the biophysical at Simon Fraser University
system, which is essential for the characterization of proteins and was recently awarded a
pathogenesis of mycobacterium involved in methicillin resistant CIHR Fellowship for young
that causes tuberculosis. Staphylococcus aureus (MRSA) investigators to pursue his
antibiotic resistance’. He is also work in ‘Elucidating the Effect
the recipient of a Vanier Canada of O-GlcNAc Modification on
Graduate Scholarship. Protein Thermostability”.

James Baylis, a PhD Candidate Steve Woosuk Hur, a PhD Paul Kim, a summer student in
in Christian Kastrup’s lab, Candidate in Dr. Kastrup’s lab, Dr. Hancock’s Lab, received a
received a Frederick Banting and received a Frederick Banting and $5 000 3M National Student
Charles Best Canada Graduate Charles Best Canada Graduate Fellowship. The Fellowship is
Scholarship. Baylis characterized Scholarship for his research awarded to students across
a self-propelling drug delivery on ‘Mechanism Regulating Canada who have demonstrated
system capable of penetrating Coagulation Factor Xllla and exceptional leadership in their
deep into the wound site. its Impact on Intracranial lives.C
Hemorrhage and Thrombolysis’.

9
research

Red Blood Cell masquerade:


polymer-mediated immunocamouflage
provides Rh D antigen-safe blood
S O L M A Z S O B H A N I FA R , PDF

Although the existence of ABO blood group antigens is


common knowledge, it is less widely known that red blood
cells (RBCs) can express more than 300 other antigens
belonging to 35 blood group systems. As such, RBCs
demonstrate extraordinary immunogenic complexity that
varies among individuals and ethnicities.
The Rh blood groups were discovered 40 years after the
ABO blood groups, and named after the rhesus monkey,
first used in making antiserum for sample blood typing.
Among 50 known Rh antigens, the Rh D antigen is the most
immunogenically and clinically problematic, second only
to ABO blood group antigens. As a result, the D antigen
poses a significant risk of acute immune response in blood
transfusions from D+ donors to D- recipients. This risk is
furthermore exacerbated in countries, such as China, where
Rh D- blood is rare, resulting in an inadequate inventory.
Dr. Mark Scott
Photo credit: Canadian Blood Services
In a recent article in the American Journal of
Hematology, Li Li, a postdoctoral fellow from Mark
Scott’s lab at the CBR, along with her colleagues developed
Macrophages “see” normal Rh D+ RBC a technique for camouflaging Rh D+ RBCs to avoid acute
anti-D transfusion reactions. Using this method, antigens are
masked by the attachment of immunologically inert polymers
such as mPEG (methoxypolyethylene glycol) to the surface
RBC membrane in a process that preserves cell morphology,
structure and function. The polymers physically hinder the
binding of problematic antibodies and avoid clearance of the
Rh D+ red blood cells by macrophages.
Li and colleagues assessed the success of mPEG chain
When Rh D+ RBC is camouflaged...
length and grafting concentration on disguising the Rh
D+ antigen by measuring antibody binding and immune-
mediated destruction of RBCs. This allowed the authors
to identify important engineering parameters, resulting in
excellent immunocamouflage of D antigens and a clinically
significant level of protection. These findings serve as a
proof-of-concept demonstrating the ability to use membrane-
attached polymer chains as a safe and effective means of
providing “D-safe” blood to recipients in areas where D- blood
is unavailable.
Americal Journal of Hematology, 90(12): 1165-1170 C

10
research

Cautiously Rethinking Pathogen


Inactivation Technology – Selective Effects
on Platelets
DEB CHEN, PHD STUDENT

Pathogen inactivation (PI) technologies further improve Christa clearly demonstrated that the total number of base pairs can robustly
blood product safety by using ultraviolet (UV) illumination predict the impact of PI treatment, with more base pairs sustaining more
and other additives to destroy pathogen nucleic acid content, damage in platelet mRNA transcripts. UV energy dose also correlates with
thereby damaging their ability to replicate and spread. As platelet mRNA recovery, where a smaller UV dose predictably caused less
expected, blood cells are not resistant to PI-treatment and damage to biomolecules. Interestingly, platelet mRNAs that remain after PI
their nucleic acid constituents also undergo a reduction in treatment appeared to exhibit longer half-lives, which may suggest activation
overall content. Christa Klein-Bosgoed, a PhD candidate in of some mechanism(s) to protect mRNAs from further degradation.
Dr. Dana Devine’s laboratory at the CBR, demonstrated that There are still many aspects of PI technology and its impact on
PI-treatment consisting of UV illumination in the presence of platelet product quality that we do not understand – as Christa comments,
riboflavin, preferentially affects specific subsets of the nucleic “This study is only one glimpse into the complex interaction between PI
acid material that is translated within platelet units prepared technology and platelet biology.” Ultimately, these studies may help to
for transfusion. fine-tune PI technology to effectively prevent blood-borne diseases while
Platelets that circulate in the blood stream are fragments preserving platelet function and therapeutic efficacy.
of their bone marrow-derived precursor, megakaryocytes, Transfusion, 56(9): 2286-2295. C
and are required to stop bleeding at the site of vessel damage.
Platelets inherit mRNA from megakaryocytes and are able
to synthesize proteins, despite the lack of a nucleus. While
the significance for platelets to actively synthesize protein is
not well understood, it is thought to be important for platelet
activation and their clotting functions.

“We wanted to better understand how PI


technology impacts platelet quality and to investigate
its still unknown impact on mRNA stability
and protein synthesis”

The safety of platelet concentrates increases with the


application of PI technology; however, PI-treated platelets
demonstrated an accelerated loss of quality, as evidenced
by increased metabolism and reduced platelet activation
upon stimulation. “We wanted to better understand how PI
technology impacts platelet quality and to investigate its still
unknown impact on mRNA stability and protein synthesis,”
said Christa. These new findings may suggest a potential
clinical impact on PI-treated platelet units, which is not yet
known and under investigation.
UV illumination in the presence of riboflavin, a potent
photosensitizer, preferentially damages guanine, one of the
Christa Klein-Bosgoed
nitrogenous bases required to build DNA and RNA molecules.

11
research

Minimizing Treatment Times for


Beta-thalassemia Major: a Small Solution
with Potential for Big Impact
ERIKA SIREN, PHD STUDENT

Beta-thalassemia is a genetic blood condition where affected


individuals are unable to produce sufficient levels of normal red
blood cells. While advances in gene therapy hold promise for a cure,
they remain at early stages of development. Currently, the primary
treatment for individuals with beta-thalassemia major is having
regular blood transfusions coupled with Iron Chelation Therapy
(ICT). ICT is required, as repeated blood transfusions cause iron
overload leading to organ dysfunction. The gold standard of ICT is
a small molecule, called desferrioxamine, or DFO (inset). However,
the short half-life of the drug (20 minutes in humans) demands 8-12
subcutaneous injections per day.
In order to reduce the burden of rigorous ICT regimens, Jasmine
Hamilton, a recent alumnus from the Kizhakkedathu research group
at the CBR, developed a high molecular weight scaffold for DFO that
increases both loading of the drug per injection, as well as the half-life
of the drug. A thousand-fold smaller than a red blood cell, a single
scaffold serves as a nanocarrier for hundreds of DFO molecules. Once
attached to the structure, the DFO conjugate exhibited significantly
reduced plasma clearance times, effectively becoming an ultra-long
circulating desferroxamine (ULC-DFO).
In the latest issue of Biomaterials, this nanocarrier was shown
to effectively clear iron overload in mouse models using only a single
injection per week. Despite circulation times of over 16 hours, no
detrimental organ accumulation or toxicity related to the introduction
of the nanocarrier were reported.
The significant reduction in dosing frequency with ULC-DFO
compared to monomeric DFO illustrates great promise in improving
the quality of life for patients with beta-thalassemia major.
When asked, “What’s next for ULC-DFO nanocarriers?”,
Dr. Kizhakkedathu stated that they are looking towards making
biodegradable scaffolds for DFO. These scaffolds will have the same
effect of ULC-DFO without the accumulation of the scaffold material
in vivo.
Biomaterials, 102: 58-71 C
Jasmine Hamilton

12
research

The Story of Beta-thalassemia:


Blood, the Sea, and a Bluebird
S H AW N A S TA N W O O D , PHD STUDENT

International Thalassemia Day took place on May 8th, and this “However, not all patients have an acceptable sibling donor.
year’s theme was “Access to Safe & Effective Drugs in Thalassaemia.” Also, even stem cell transplantation with fully matched siblings
Dedicating a day in the calendar for thalassemia is well-justified. carries risk, including transplant associated mortality,” adds Dr. Au,
According to the World Health Organization (WHO), “the alpha who collaborates with Dr. Ross MacGillivray (Centre for Blood
and beta thalassaemias are the most common inherited single-gene Research) and works at BC Children’s and Women’s Health Centre.
disorders in the world with the highest prevalence in areas where Recently, a potential treatment option for beta-thalassemia
malaria was or still is endemic.” major in the form of gene therapy has attracted much attention.
Originating from “thalassa” and “haema,” the Greek words for In early 2015, a press release revealed that a drug product called
sea and blood respectively, thalassemia is a hemoglobin disorder. LentiGlobin® BB305 by a company called Bluebird Bio, Inc. had been
Beta-thalassemia refers to thalassemia with decreased or absent beta- deemed a Breakthrough Therapy by the United States Food and Drug
globin production, a component of hemoglobin. Administration.
Beta-thalassemia minor, or beta-thalassemia trait, either This press release stated that “LentiGlobin BB305 Drug Product
does not manifest any symptoms or may result in mild anemia. aims to treat beta-thalassemia major and severe sickle cell disease by
Beta-thalassemia intermedia may produce a range of challenging inserting a functional human beta-globin gene into the patient’s own
symptoms, such as gallstones, jaundice, and leg ulcers. Consistent hematopoietic stem cells ex vivo and then returning those modified
blood transfusions are usually needed for patients with the most cells to the patient through an autologous stem cell transplantation.”
severe of the beta-thalassemias, beta-thalassemia major. However, even though gene therapy has made a big splash, the
According to the National Institutes of Health (NIH), blood story is still not entirely complete. Dr. Au points out that “the long
transfusions, iron chelation therapy, folic acid supplementation, and term efficacy and side effects of the current gene therapies still need
stem cell transplantation can be used to treat thalassemia. to be determined.”
Dr. Nick Au, a clinical assistant professor in the Department of Looking toward the future, he anticipates that “although recent
Pathology and Laboratory Medicine, says that currently, only stem therapies show some promise, the ultimate goal of developing
cell transplantation can be curative. He elaborates that the stem cells a permanent cure that offers a better risk profile than stem cell
are usually obtained from a patient’s sibling who is immunologically transplantation and that is predicted to work in all patients likely still
similar, which reduces the morbidity related to the procedure. requires more research and work.” C

13
research

Small Parts of a Big Problem –


Uncovering the Molecular Basis of Obesity
TA R A F E R N A N D E Z & M I C H E L L E K W O N
Resisting the urge to reach for that donut, or taking the stairs As Michelle explains, “There has been an enormous interest
instead of the elevator - we all know that eating healthy and staying in trying to therapeutically target brown adipose to lower
active helps in the battle of the bulge. Still, obesity remains an ever- circulating fats.” Indeed, this represents the holy grail of anti-obesity
growing global concern, with a whopping 60% of Canadians found therapeutics, in which those late night pizza indulgences would
to be overweight. Considerably less is known about the molecular simply be burnt off as heat, and not through hours of sweating on the
mechanisms that orchestrate the physiology of fat tissue, and their treadmill. Fascinatingly, Michelle and her lab have also discovered
relation to the plethora of obesity-related conditions, such as heart a role of brown adipose in resisting diabetes. “Our studies highlight
disease, stroke and diabetes. that brown adipose metabolism can also be harnessed to lower blood
A collaborative project between two young researchers at sugar levels in experimental models of diabetes”. Michelle adds,
UBC’s Centre for Blood Research (CBR) and the Diabetes Research saying she looks forward to exploring whether igniting brown fat
Group (DRG) hopes to change that. Together, they are uncovering activity has a potential in a clinical setting.
compelling new facets to the development of obesity and diabetes on Zooming in on the cellular characteristics that distinguish
a cellular level – with the hopes of revolutionizing preventative and brown and white adipose is Tara’s main research focus. Exciting new
therapeutic strategies against these diseases. discoveries from the Conway lab are revealing that proteins present
Michelle Kwon, DRG graduate student in Dr. Timothy on the surface of fat cells may hold the key to brown fat’s energy-
Kieffer’s laboratory and Tara Fernandez, Postdoctoral Fellow with burning properties. Tara shares some insights into the progression
Dr. Ed Conway’s team at the CBR are working on a collaborative of these novel findings, saying “Initially, we were interested in the
venture to study the intricate interplay between fat tissue and role of these proteins in inflammatory conditions. Surprisingly, these
metabolic regulation. Specifically, they are interested in identifying molecules also control how fat cells grow and behave.” Using a range
the biological cues that govern fat cell growth and function. By of cell-based and molecular biology platforms, clues as to how this
combining their expertise on different experimental models of molecule fits within network of pathways that govern weight gain and
obesity and methods for analyzing fat’s metabolic potential, Michelle glucose metabolism are slowly being uncovered.
and Tara hope to shed light on how to harness these pathways Expanding collaborative networks is one of the most essential
clinically. means of solving formidable biological problems. Indeed, both
Fat, or adipose, is a complex tissue, mainly functioning as a Michelle and Tara have experienced this first hand through this
lipid repository of the body’s energy reserves, but also important joint research venture. “It’s great to bounce ideas off each other,” they
in producing various hormones and thermoregulation. ‘White fat’ said about their team effort, adding that their different perspectives
constitutes 20-25% of human body weight, with obese individuals drive the project in ways that would not have been possible if done
having markedly elevated white fat levels. On the other hand, the in isolation. When they are not making waves in the lab, Michelle
relatively recently discovered ‘brown fat’, is a highly specialized is putting her laboratory skills to good use in brewing the perfect
adipose tissue which acts as a furnace, utilizing sugar and lipids as ale and baking delicious breads, while Tara enjoys playing Ultimate
fuel to generate heat energy. Frisbee and the ukulele. C

14
research

Host Defence Peptides


PRASHANT KUMAR, P H D C A N D I D AT E

Host defense peptides (HDP; also known as antimicrobial peptides) are short multiple signaling pathways that are involved in immunity
positively charged peptides produced by animals, insects and plants. Originally, and inflammation, which may explain their wound healing
these peptides were thought to only have direct antimicrobial activity against a ability. Early clinical trials with LL-37 have revealed an
broad range of microorganisms, such as bacteria, fungi and viruses. However, many effective topical treatment for hard to treat venous leg ulcers.
new studies revealed that HDP also play an important role in immune modulation,
wound healing, and diseases, such as cancer and autoimmune disorders. Recently, Relationship between HDPs and Disease
Dr. Evan Haney and Dr. Erin Gill from the Hancock Lab at the CBR published
a review article in Nature Review summarizing the different functions of two HDP expression is tightly controlled in the skin,
human host defense peptides – cathlicidin LL-37 and defensins – and their lungs, gut and circulatory system. Dysregulation of many
relationship with various diseases. natural HDP correlates with disease onset and progression
depending on the location. LL-37 is normally produced in
Immunity and inflammation sweat and mast cells of healthy skin but is overexpressed in
the skin of patients with psoriasis. Atopic dermatitis and
Human cathelicidin LL-37 and defensins are expressed in many cell types, some skin infections are also related to LL-37 and defensins
including epithelial and immune cells such as macrophages, monocytes, natural regulation.
killer cells and neutrophils. Interestingly, these peptides elicit both pro and anti- In pulmonary diseases, such as cystic fibrosis,
inflammatory response depending on the cell type and stimuli. For example, LL-37 characterized by a mucus build up and colonization by S.
can induce histamine release from mast cells, but produce an anti-inflammatory aureus and Pseudomonas aeruginosa bacteria, synthetic
response in B-cells, and T cells. The peptides can also directly attract various HDP have shown therapeutic promise. They are able to
immune cells. directly target the bacterial infection and can dampen the
Additionally, defensins have unique properties to activate platelets and hyper-inflammatory response.
promote stem cell migration in skin and intestinal epithelial cells. HDP influence Moreover, some studies illustrated that mice without
the cathelicidin gene had tumors that grew faster and
their NK cells had impaired activity against tumors.
Counterintuitively, LL-37 was overexpressed in cancer cells
and stimulated tumor growth and proliferation. Blocking
the interaction between LL-37 and specific tumor cell
receptors impaired tumor cell growth.
Similar to LL-37, increased levels of defensins in
patients with cancer suggest that it might also promote
tumor cell proliferation. However, it might also just reflect
an aberrant host response. These studies show that there is
much to be learned about the role of HDP in cancer.
HDP are complex signaling molecules that are involved
in immunity, inflammation and different diseases. It should
be emphasized that HDP do not act on specific signaling
pathways in their effector cells and hence a systems biology
approach is needed to fully understand the roles of HDP and
identify novel therapeutics.
Nature Reviews Immunology,
16: 321-334. C
Human defense peptides are now known to be involved in both direct microbial
killing and immune modulation.
Hancock, R. E et al. NatureBiotech. 2006, 24, 1551−7

15
major events
Students of the Summer Studentship
Program with Dr. Andrew Trites

RESEARCH DAY IN REVIEW


Tara Fernandez, Houra Loghmani Khouzani, Victor Lei, Linnette Mae Ocariza, Erika Siren

Every year, the Center for Blood Research holds the CBR Research Day to celebrate the achievements of its undergraduate summer
students and to showcase the work and talent of their graduate and postdoctoral researchers. The CBR works to facilitate career development
with the Summer Studentship Programme, providing undergraduate students the opportunity to develop their own research project with the
guidance of mentors, as well as attend a series of skill building workshops and tours. On August 16th, the LSI Atrium was filled with enthusiastic
members of the CBR, eagerly awaiting the start of Research Day, to learn about each other’s accomplishments.
The Summer Student presentations started off the day soon after lunch. Dr. Ed Conway, Director of the CBR, took to the mic to explain the
strict rules for the talks. His final words echoed through the seminar room ominously… ”Three…minutes…ONLY.” The designated timekeeper,
Victor Lei, was seen lurking in the shadows, gently cradling the CBR Research Day’s official mascot, the sacred rubber chicken. After an elapsed
time of 3’30”, Victor was instructed to subject the chicken to repeated rounds of violent asphyxiation. Its shrill, piercing cry was a stark
reminder that the student’s stage time had indeed run out.
Reminiscent of a scene from the Hunger Games, the Summer Students anxiously adjusted their bowties, inspired by the attendance of new
UBC President Prof. Ono, and tried in vain to hide their sweat patches, while stealthily checking out their competition. In the distance, a raven
cawed, signaling the commencement of the day’s proceedings.
The first speaker, Amarpreet Grewal, set the bar extremely high with her eloquently presented description of her summer’s achievements.
Hailing from the CBR Admin team, Amar detailed her efforts at promoting CBR’s education and engagement initiatives, while attempting to
create a CBR-based viral sensation on social media.
What followed was a stream of enthusiastic students taking to the stage to share their scientific endeavors in a packed seminar room.
The audience was treated to talks describing everything from HIV drug resistance in Swaziland to advances in high throughput diagnostics for
cancer. The students tried every tactic under the sun to engage their listeners: rhetorical questions, shocking factoids, stories, metaphors, and
endless jokes, inspired by the UBC 3 minute thesis competition. Even senior graduate students were left feeling inadequate after learning what
these undergraduate students 1ts could achieve in just a few short months.

16
The next award paid tribute to the people who enabled and best 3 minute talk, and preparing for the arrival of the new UBC
supported the young researchers at the CBR. In honor of Neil President, Professor Santa Ono.
Mackenzie, the CBR offers an award in his name to recognize the Prof. Ono arrived in the midst of poster judging and took
mentorship excellence in the CBR community. This year, Dr. Evan the center stage in the atrium next to the brand new CBR poster,
Haney, a postdoctoral fellow in the Hancock lab, is the recipient of this designed by Amarpreet Grewal just one month prior. As attendees
award. He is described as a caring, friendly, generous and enthusiastic discovered the President’s arrival, the excitement visibly grew. After
mentor, who goes out of his way to help his colleagues and to make a wonderful introduction by Dr. Ed Conway, Prof. Ono talked to the
the lab a great place to work. CBR researchers about his early research career in immunology and
the nostalgia he feels for the graduate student days.

(L-R): Drs. Ed Conway, Evan Haney, Dieter Bromme

After the award presentation, Dr. Andrew Trites of UBC’s


Marine Mammal Research Unit took to the stage for his keynote talk:
“Expecting the unexpected in science education”. He encouraged
the crowd of young scientists to allow their innate passions form
their professions. Dr. Trites shared how he combined his interests
in the life sciences and for investigative work in order to take on a
“missing seals” project early in his career. After taking this project, Dr.
Trites fell into many intellectually fun and unexpected opportunities
that he shared with his audience. He consulted the Royal Canadian President Santa Ono
Mint on coin design, helped settle a fishing rights dispute for a First
Nations group, and led the Blue Whale Project, excavating Canada’s At the end of his talk, President Ono awarded the best
largest Blue Whale skeleton, which is now displayed in UBC’s presentation prize to a very surprised Evelyn Liu from the McNagny
Beatty Biodiversity Museum and is featured in a Discovery Channel lab. As his final act, he stayed to view the graduate student posters
documentary. In case you are visiting it, the Biodiversity Museum also and talked science past the allocated time, until he was pulled away
has Pokémons! by calls from his wife! Shortly after, Dr. Conway presented Elana
The next chapter of the day featured 14 graduate and Kimmel from the Cote lab with the best poster award; and Ryan
postgraduate judges, who challenged the summer students Hope from the Harrigan lab received the rubber chicken for the
to demonstrate their knowledge with poster presentations. longest, albeit stimulating student talk.
Undergraduates were evaluated on poster design, presentation, and The day ended with a delightful barbeque dinner and drinks.
ability to answer questions about their work. In the meantime, the All and all, it was another successful and fun event at the CBR,
Admin team was secretly and frantically calculating the winner of the looking forward to more! C

17
major events

CBR Hosts: The First


World Thrombosis Day in Vancouver
Amarpreet Grewal, Anna Sinova

The Centre for Blood Research (CBR) participated in World


Thrombosis Day - a global movement to raise awareness about thrombotic
disorders: deep vein thrombosis, pulmonary embolism and venous
thromboembolism – by hosting the first World Thrombosis Day event in
Vancouver on October 13th 2016. World Thrombosis Day was founded in
2014 by the International Society of Thrombosis and Haemostasis (ISTH)
in response to members’ requests for a focused global awareness day on
thrombosis, and with the aim to combat thrombosis-related disorders. It
is recognized globally on October 13, the birthday of Dr. Rudolf Virchow,
a pioneer in the pathophysiology of thrombosis. The ISTH mission is to
reduce the number of premature deaths from thrombosis by 25% by 2015.

The ISTH mission is to reduce the number of premature deaths from


thrombosis by 25% by 2025.

The CBR was the first in Vancouver to host this public education
event on thrombosis and stroke. On the evening of October 13, CBR staff
and volunteers welcomed members of the community, patients and
various professionals at the Life Sciences Building on UBC Campus. Each
attendee received a gift - a CBR tote bag and a 14 day Gold’s Gym pass –
and then was free to enjoy tasty food, live music and to visit booths from
10 different organizations.
Photo credit:

Community centers, health consultants, support groups and


pharmaceutical companies, all came together to support the World
Thrombosis Day message and to connect with the public, by holding a
World Throm

booth at this CBR-hosted event. Iridia Medical held a “Chain of Survival”


demonstration, offering attendees the opportunity to practice their CPR
skills on a mannequin. Likewise, North Shore Stroke Recovery Centre got
everyone’s brain working hard when it came to naming flowers based on
bo

the first letter of the alphabet. Love Your Age provided blood pressure
sis Day

checks and gave away free pedometers, and Dieticians engaged everyone
in ranking the salt content of various common foods. The hands-on
experiences at the booths, were not only entertaining, but also empowered
participants to take control of their well-being by learning causes of
disease, risk factors, signs/symptoms and methods of prevention.

As a result of this event, we have built new partnerships and raised much-
needed funds to support CBR-sponsored educational programs!

18
After enjoying the booths, everyone moved to the lecture hall for
cheery and highly informative presentations by the guest speakers: Dr.
Agnes Lee, Physician and Clinical Thrombosis Program Head at the
Vancouver General Hospital, Dr. Ed Pryzdial, Scientist at the Canadian
Blood Services and Associate Director of the CBR, and Dr. Wesley Pue,
Professor of Law at UBC and a patient with a history of thrombosis.
Dr. Lee discussed the issues surrounding the clinical aspects
of thrombosis and the differences between myocardial infarction,
pulmonary embolism, stroke and deep vein thrombosis. She
emphasized how important it is that individuals become informed, and
that they learn how to reduce their risk. Her vast experience was much
appreciated by the audience, as was evident by the stream of questions
following her presentation.
Dr. Pryzdial energetically, and with an ever-present humor, took
everyone on a PowerPoint tour of his research that culminated in a
description of his lab’s recent discovery of a promising new therapy for
thrombosis. His group recently patented Xai-K (pronounced “ten-eh
K”), a drug that can selectively target the problematic clots, and can
either enhance currently available therapeutics, or can function as a clot
buster on its own. His presentation featured time lapse videos and was
spiced with quizzes and prizes, which did not fail to inform, as well as to
amuse.
The talks culminated with Dr. Welsey Pue’s personal story on how
blood clots affected him, starting from the day he was diagnosed to
the problems he faced along the way. His talk was a great reminder
of the importance of awareness and prevention, the value of family
support, and, also, why scientists and physicians must communicate
with patients and the public. This final talk also stimulated considerable
discussion, as several attendees shared their own stories, and engaged
in an open forum, with input from the experts, Drs. Lee and Pryzdial.
As a result of this event, we have contributed to increasing
awareness and understanding of thrombotic disease. Hopefully this
will trigger a daily effort to prevent thrombosis, and to identify new
solutions for this common, disabling and sometimes fatal disorder.
Donations from attendees will go towards thrombosis-related
education programs at the CBR. We also established new partnerships
with a number of local organizations.
We would like to thank everyone who contributed to the success
of World Thrombosis Day: all CBR members who helped promote
and organize the event; Brian Kladko for communication and media
consulting; all the vendors and musicians; and Drs. Ed Conway, Agnes
Lee, Ed Pryzdial, and Wesley Pue for their stimulating presentations.
And of course, we particularly wish to thank all those who attended the
event, and committed to increasing awareness of thrombosis.
See you next year! C

19
major events

“Critical Skills for Success Conference” -


the Student Led Initiative
Andrew Alexander, Pierre-Marie Andrault, Jenny Chik, Houra Loghmani Khouzani, Chanel La

Graduate Award Program students


with Anna Sinova.

The Graduate Award Program (GAP) students from the Two sessions of three parallel talks highlighted the diversity
Centre for Blood Research were tasked with organizing an event, of professions that people with a PhD in science can pursue,
as part of their program requirements. After long deliberations whether they have an academic appointment or not.
they have settled on a topic that is close to everyone’s academic Three of the speakers who had an academic appointment,
heart. Seeking jobs after graduating in life sciences can seem talked about the variety of directions one can pursue
like a daunting task, and therefore knowing the different options independently or in parallel to a research career.
available can help enormously in choosing the right path. With Dr. Mark Winston, a Professor in SFU Biological Sciences,
the “Critical Skills for Success Conference” held on July 22, 2016, is also the Founding Director of SFU Centre for Dialogue and the
they aimed to expand their own and their peers’ horizons both in 2015 Governor-General’s Award-winner for his bestselling book
academic and non-academic directions. They invited 6 excellent “Bee Time: Lessons from the Hive”. In his workshop, he took the
speakers with diverse viewpoints to share their passions and approach of a dialogue with the participants, making a refreshing
advice in the workshops and a panel sessions. The career paths shift from PowerPoint presentations. Dr. Winston highlighted
represented were academia, clinical research, industry, science the need to practice distilling one’s research in an approachable
communication, business consulting and science policy. manner, so that it can be understood by a non-specialized
audience. Parallel to his work in academia, he creates spaces for
The goal of the conference was to expand their own dialogue on complicated issues, leading engaged discussions on a
and their peers’ horizons both in academic and wide variety of policy issues, from city planning to LGBT rights, all
non-academic directions. around Vancouver.

20
Dr. Mark MacLachlan, a Tier 1 Canada research chair such as personality fit, leadership and initiative taking.
in supramolecular materials at UBC, also loves teaching. He Her career path took her from her postdoctoral studies
is a recipient of the Killam Prize for Excellence in Teaching in Sweden to the R&D in industry in Vancouver. You can
and bears a distinct resemblance to Leonard Hofstadter of read more about her career path in her interview with the
the Big Bang Theory. An xperienced and energetic lecturer, International Society for Stem Cell Research.
he emphasized the importance of catering to one’s audience Dr. Agatha Jassem, a Clinical Microbiology Fellow at
and highlighted some tips and tricks of audience engagement National Institute of Health, discussed her unusual career
when teaching. A prime example of this lesson is seen in his edging between a scientist and a physician. In this session,
interview with the Vancouver Sun, where he shares his passion she talked about her job as a clinical researcher. In this
for inventing new materials and simultaneously gets the profession, she oversees a diagnostic lab and works side
readers excited about Chiral Nematic Mesoporous Silica. by side with physicians and patients. The goal is to provide
prompt, accurate diagnoses of infectious diseases which
Even the negative results are important to the context involves significant lab responsibilities. Her lab work is
of current medical knowledge used for patient-specific “detective” work, as compared
to research, where experiments are meant to lead to new
Similarly, Dr. James P. McCormack, professor at the discoveries impacting patients in the future. To become an
Faculty of Pharmaceutical Sciences at UBC, has found his accredited clinical researcher, she is currently completing
passion in teaching through podcasts –he is a co-host of a 2-3 year fellowship program, which closely resembles
the award-winning Best Science (BS) Medicine Podcast. In medical residency.
his Science Communication workshop, he highlighted the Dr. Cara Ferreira is the Engagement Manager at
McKinsey Global Management Consulting. McKinsey
Consulting is a global giant, using teams of PhDs to
consult on management decisions across the public and
private sectors. In her business consulting workshop,
Dr. Ferreira pointed out that the specific area of one’s
PhD is not important, as McKinsey Consulting hires all
different backgrounds. The important qualities that they
look for when hiring new graduates are the ability to think
critically, have a problem solving mindset and demonstrate
intellectual curiosity.
Dr. Mark Winston speaking The workshops were followed by a panel discussion
to CBR students where participants could ask questions from any of the
speakers. Having a panel of professionals from such diverse
importance of remaining vigilant about medical stories. In an career paths was very inspirational and provided great
interactive session, the audience was asked to evaluate an advice for all attendees. The conversations then continued
online CNN medical article, learning to keep a critical outlook over wine and cheese for several hours facilitating new
on science in the media. The workshop emphasized that data relationships. A deeper look into the work-life balance of
are relative to the context of current medical knowledge and these successful individuals along with their unwavering
that even negative results are important: “it’s also important to sense of humour brought hope to current graduate students
show that something doesn’t work”. Useful tools and tips can and postdoctoral fellows in the audience. All in all, another
be found at www.healthnewsreview.org. perfect day for learning at the CBR! C
Three other speakers discussed their non-academic
professions and shared their insights into pursuing unique
careers post-PhD.
A workshop on resume writing and interview skills
presented by Dr. Jennifer Moody, a VP for Commercialization
at the Centre for Commercialization of Regenerative
Medicine in Toronto, started off with insightful coverage on
proper resume writing for an industrial position. She taught
how to “communicate your Value proposition”, meaning
to demonstrate one’s added value through a resume and
interview. It involves highlighting one’s key accomplishments
and addressing specific skills that make one suitable for
the desired position. Dr. Moody was very honest in what
interviewers may look for in the industry from recent graduates, Mentor panel session.

21
programs

Get the Scoop:


What is the Health
and Wellness
Committee?

A M A R P R E E T G R E WA L

The Centre for Blood Research has formed its Linnette Mae Ocariza, Research Technician in Dr. Ed Conway’s Lab
Health and Wellness Committee! They envision the (President)
creation of an inclusive, supportive and connected Q: How does the Health and Wellness Committee benefit you?
community by engaging in social and physical A: Not only has it been a lot of fun planning and bouncing off ideas with others,
activities. Based on interviews with some CBR it has given me an opportunity to grow my organizational, communication, and
members, it was noted that the biggest challenges leadership skills. Not to mention it has made it easier to connect with other CBR
in working in a laboratory setting were high levels of members.
isolation, stress and lack of opportunities to connect
with CBR members outside of one’s lab. Jenny Huang, Technician in Dr. Ed Conway’s Lab (Admin Officer)
Maintaining a work/life balance is difficult, Q: What events are you looking forward to?
especially if one plays many roles. Taking that into A: We have an upcoming CBR MOA tour – I am really excited about it. I have
consideration, the Health and Wellness Committee only been to the MOA once! It’ll be even better with a guided tour. I am also
is planning events that are family-friendly and will looking forward to some of our future events (in the making) – such as cooking
target various interests and commitment levels. classes, yoga etc.
The group is hoping to improve psychological and
physical well-being, as the events expose CBR Diana Canals Hernaez, MSc Student in Dr. Kelly McNagny’s Lab (Committee
members to new skills, new ideas, and physical Member)
activities to help elevate stress and expand social Q: Why did you join the Health and Wellness Committee?
networks. A: Since I started grad school, I have been interested in improving the wellbeing
So far, the Health and Wellness Committee of graduate students. Science research is a highly competitive environment.
was behind the awesome events, such as Bubble Graduate students are often under a lot of pressure: expectation to produce
Soccer event, Lynn Valley Hike, and Hawaiian good results, publish in high impact journals, and meet grant deadlines.
Staycation party. Together this can affect, both physically and mentally, the health of graduate
Here’s what some of the members have to say students. I joined the Health and Wellness committee to try to improve and
about the committee: alleviate part of this stress. Also, it has given me the opportunity to work
alongside other CBR members. C

22
opinion

“Learn by Doing”: Sunny Park, Tea Yates

Mutual Gains of Mentorship


A B H I N AV A J AY K U M A R , P H D C A N D I D AT E

As part of the mentorship program, Sunny and Tea spent a It was refreshing to move away from the world of “p-values”
month in the Côté lab assisting me on a project that investigated the and “statistical significance” and spend multiple afternoons with
effects of maternal HIV antiretroviral drug burden during pregnancy Sunny and Tea engaging in educational discussion regarding the
on infant mitochondrial DNA. While working in the lab, Sunny and Tea goals of our project and the questions we hoped to answer. In the
were able to gain technical knowledge on how to extract DNA from process, I learned to tell a story, rather than just burying them with
blood, as well as hands-on science experience quantifying DNA via interconnected scientific facts. Moreover, by challenging them to
PCR and separating DNA fragments via gel electrophoresis. At the think on their own and come up with their interpretation of our
same time, they were able to broaden their theoretical knowledge on experimental results, I was able to understand their take on our story’s
topics, such as the epidemiology of HIV infection, the HIV life cycle ending. Within a short time, I saw myself grow from a good instructor
and how different antiretroviral drugs inhibit viral replication to curtail to a good teacher.
its spread.
From handling a pipette for the very first time to setting up “Before I started the mentorship program, I was only 80% sure
PCR plates on their own, the confidence they showed in mastering about going into the sciences. Now that I have had hands-on
complex molecular biology techniques was a reward in itself. Being experience in the program, I am certain that I will pursue a career in
involved with the Centre for Blood Research community for the the sciences” says Sunny.
past three years, I have been fortunate to witness the emphasis
that this organization lays on knowledge translation. In its pursuit of Such is the dilemma faced by most high school students
promoting research excellence, the CBR has been a front-runner in whereby they are stuck at this “80% sure” state and unable to zero
providing unsurpassed training experiences for its many scientists down on a career path.
and student trainees. Our success is not measured in the number of “This mentorship opportunity not only taught me about HIV and
scientific publications, but in the wealth of knowledge shared among antiretroviral drugs, or how to perform a bunch of cool assays, but
the community. In keeping with this, the CBR has recently diversified more importantly showed me what being a scientist is all about and
its quest for knowledge dissemination among people of all ages, by whether I could see myself as one down the line” says Tea.
providing hands-on research experience to some of our city’s young, By providing students an all-inclusive first-hand experience
bright minds through the high school student mentorship program. into the day-to-day life of a modern scientist, therein lies the most
I was fortunate to aid in the endeavors of the CBR community by valuable contribution that such “learn-by-doing” science mentorship
serving as a mentor to Sunny Park and Tea Yates, two Grade 10 programs have to offer. This may help paint a clearer picture of what
students from the Prince of Wales Mini School, Vancouver. a career in science entails and in turn may be the deciding factor that
Any mentoring relationship can be beneficial to both the tips the “surety scale” from 80% to 100%.
mentor and the mentee, personally and professionally. What By taking this opportunity to share my experiences and impart
set this particular experience apart from any of my previous knowledge to my mentees, it was personally satisfying to know that
mentorship activities was how working with someone substantially I may have instilled a genuine passion for research among them and
less experienced than myself encouraged me to step outside the contributed in one way or another to their growth and development.
regularities of scientific reasoning and look at things with a new Along with being a highly educational experience for all three of us, to
perspective. quote Sunny and Tea – “it was definitely worth it!” C
23
opinion Green Fluorescent Protein.

Olga Zamudio (centre)

CBR Finalist in the


ACS Chemistry
Champs Contest
Amarpreet Grewal, Anna Sinova

On August 20, 2016 Olga Zamudio Prieto from Dr. visuals for our presentation, as well as for our on-stage
Dieter Bromme’s Laboratory at the CBR was one of the four delivery. I learned a lot from the experience, so I felt I’d
finalists who received a fully paid trip to Philadelphia for the already won even before the finals were even a possibility.”-
American Chemical Society (ACS) Chemistry Championship recalled Olga about Round 3.
Finals. The Semi-Finals involved a 3 minute live performance
The aim of the Chemistry Champions Contest is based on the training received. The contestants were judged
to record a short video of one’s chemistry research or a on their performance and original video by an audience.
concept to engage the public, raising scientific literacy and Only 4, with Olga among them, were selected to continue
providing more support for science. on the journey to the ACS Chemistry Championship Finals
Olga learned about the ACS Chemistry Champions held at the Franklin Institute in Philadelphia.
Competition while watching the ACS Reactions Youtube The Finals involved a series of live shows. One event
channel and she decided to try herself out. “I think the ACS was an annual outreach event at the Franklin Institute, where
Chemistry Champions Competition doesn’t have as much they talked to an audience of families and kids. The last
promotion as it should”- she shared. event was held at The Fields Sports bar with three science
She started with creating a 2.5 minute video about the communication professionals judging the competition and
Green Fluorescent Protein (GFP). Although her research an audience from the ACS National Meeting. Olga won
is on proteases, she decided that a video about GFP as second place at the ACS Chemistry Championship Finals!
a science tool would be more eye-catching and grab the As runner-up, she was invited to be a guest at the ACS
attention of an amateur scientist audience. Competing webinar. The winner, Mallory Hinks from the University of
against many applicants, Olga and 11 other entrants were California, received a trip to Washington, DC to network
selected to continue to the second round, where they were with professional science communications staff at ACS and
challenged to excite the listeners about a unique element a 3D-printed Chemistry Champions trophy.
from the periodic table. Olga received the element Arsenic “Overall, the experience was really fun, I could share
and created a fun video discussing its history, including something I’m passionate about and on top of it, I was
famous deaths from arsenic poisoning, controversial history rewarded! At the CBR we are lucky to have the Knowledge
of its use in household products, and finally its current Translation team, where you can explore and develop
applications. Olga’s excellent video was selected to move to different communication skills. At first, I wasn’t confident,
the next level of competition with seven others to the ACS because English is my second language, but I’m so glad
Semi-Finals. I didn’t hear my internal saboteur! I would invite any
The Semi-Finalists went to the ACS Headquarters in undergraduate or graduate student to participate in the next
Washington, DC for a two-day science communication year’s championship. If you are between 18 and 35 years of
workshop. “They gave us social media advice, we did improv age, you can participate!” C
exercises and we got tips and feedback on the design and

28
24
people

The founding of the CBR:


Ross MacGillivray interview
Jenny Chik, a Postdoctoral Fellow in Dr. Leonard Foster lab, interviewed one of the founding members of
CBR, Dr. Ross MacGillivray on his reflections about its past, present and future.

What is the CBR trying to accomplish?


The CBR was started to try and take advantage of new opportunities in
funding that came about at the turn of the millennium. Dana Devine, Grant
Mauk, Don Brooks, Charles Haynes and I got together and thought we
should get contiguous space for people at UBC who were working in the
general blood area so that we could work together more efficiently.

What was your dream for the CBR in the first 10-15 years?
The original dream was to advance transfusion science, particularly
with blood products. We have advanced that quite well. Some of the
collaborations in the CBR have been wonderful and definitely wouldn’t have
happened without moving into this building. If you look at the academic
productivity of the CBR, it has exceeded what we had hoped for when we
first came into the building.

Do you think the mission of the CBR has altered during its existence?
Absolutely. It has changed a bit since I stepped down as director. We
If you could name one achievement of the CBR that you are
deliberately recruited Ed Conway who was a clinician-scientist, and there
most proud of, what would that be?
were two things that we really wanted to achieve in our 2008 Strategic
The fact that we set up the Centre and we are now recognised
Plan: we needed collaborations with clinical departments and we needed
as a national and international centre of excellence in blood
more fundraising from individual donors and pharmaceutical companies. Ed
research is a great accomplishment – especially as it came from
Conway has really developed the CBR along these lines beyond our wildest
scratch.
dreams. Because of that, we’ve also changed our mission a little bit so it’s not
restricted to transfusion science, but it also involves immunity & infection,
What do you envision to be the future of the CBR?
biomarkers as well as haemostatic balance.
I would like to see Ed Conway’s second term completed with
closer relationships with the clinicians. I would like to see two or
How does the role of being a Director of the Centre impact on your
three assistant professors come in to the CBR space to replace
academic career?
people who have retired and thus maintain the research that we
I was very fortunate in that there were two people in my lab – Jeff Hewitt
have going. And I would like to see the CBR have more stable
and Val Smith who were both with me before we moved here. Having those
funding so that we can continue working on the blood area as a
two people in my lab really helped maintain research directions and progress
recognised centre. Each of those has their own challenges but
with new techniques. They made the whole difference so that I could spend
they are challenges that we can certainly meet.
time on administrative work as well as enjoy doing my own research.

Do you have any final comments to add?


How does the CBR compare with other Blood research institutions in
I think it’s been a wonderful experience. We can all be proud of
Canada and the world?
the research and educational aspects that we’ve developed over
We are unique in that we have a collection of clinician-scientists and
the last 15 years in the Life Sciences Centre.
scientists working in the blood area. But in addition to that, we have had
sociologists, dentists and engineers. So that separates us from other blood
We would like to thank Professor Ross MacGillivray for his time
research centres in the world that tend to just concentrate on biomedical
research. dedicated to the interview. C

25
tribute

Professor Donald Metcalf –


A tribute to the legend (26 February 1929 – 15 December 2014)
P I Y U S H K U M A R K A P O PA R A , PDF

of Nobel Laureate Sir Frank Macfarlane Burnet at the Walter and Eliza Hall
Institute, Australia. It was only later that he transitioned to study hematology.
He undertook postdoctoral work at Harvard Medical School for two years,
subsequently returning to the Walter and Eliza Hall Institute as Head of the
Cancer Research laboratory. In 1966, Prof. Metcalf assumed the position of
Deputy Director of the same institute.
Over a period of fifteen years, Prof. Metcalf and his colleagues identified and
purified four hormones leading to the discovery of so-called ‘colony stimulating
factors (CSFs)’, referred in that way, because they stimulated the production of
white blood cells.

His discovery of CSFs revolutionized the way cancer is treated, benefitting


an estimated 20 million patients worldwide.

Cancer patients undergoing chemotherapy often suffer from a depletion in


their blood cells, leaving them vulnerable to infection. Prof. Metcalf speculated
that there must be something that regulates white blood cell turnover, which
Last week, as I was looking for motivation to could pave the way to tackle this side effect of chemotherapy. Treatment with
perform my blood clot analyses and mindlessly CSFs is now standard practice and every year the number of people who survive
flipping through a forgotten issue of The Scientist on because of his work grows. His discovery also revolutionized transplant medicine
my desk, I stumbled across an article entitled, “The by providing new techniques for bone marrow transplantation for blood diseases.
Father of Modern Hematology Dies”. What shocked There can be no greater legacy for a medical researcher.
me was, sadly, not the fact of his death, but rather that Practical, loyal, and hardworking were the qualities that he possessed, as
I didn’t know who he was, particularly as I am now a described by Prof. Hilton, director of Walter and Eliza Hall Institute of Medical
postdoctoral fellow in hematology. This lapse had to Research and division head for Molecular Medicine. One excerpt from his tribute
be corrected! And here I would like to share with you to Prof. Metcalf also provides a clue into the inner life of his laboratory:
my discovery of this inspirational scientist and leader, “Upon a new recruit starting in his unit, it was mandatory for them to meet
and try to answer a question that is on everyone’s mind: with Don, who, at least until the mid-1990s, would be smoking a cigar, and would
How does one become a father/mother of an entire lull you with a question like “have you had a good holiday” – inviting a response
field of knowledge? like, “yes, thank you Professor Metcalf, I have had a lovely two weeks camping
Professor Donald Metcalf was a titan of his field, at Wilson’s Promontory” – which was then followed by “excellent, that’s the last
studying, among other things, the production of blood holiday you will have for three years, get to work”. And it was the last holiday you
cells, cell survival, suppressors of cell signalling, and took, not because Don would stop you taking leave, but because his hard work
stem cells. was infectious and the lab would become your world”.
Although he officially retired in 1996, Prof. Metcalf, continued his research,
Practical, loyal, and hardworking were the studying the regulation of normal and leukemic blood cells. And even after
qualities that he possessed. being diagnosed with metastatic pancreatic cancer in August 2014, for which
he himself underwent chemotherapy, he continued to work. He performed his
Donald Metcalf was born on February 26, last experiment in October and passed away surrounded by his family on 15
1929 and studied Medicine at the University of December 2014 at the age of 85.
Sydney. Before embarking on his research on Prof. Metcalf ’s autobiography entitled “Summon up the Blood: In dogged
leukemia, he studied vaccinia virus in the laboratory pursuit of the blood cell regulators” was published in 2000. C

26
tribute

Mourning the loss of


Dr. Sheldon Naiman
1937-2016

On July 24, 2016, we lost a wonderful person, and longtime


friend of the CBR and many others. Shelly and Linda were
Dr. Sheldon (Shelly) Naiman was born in Toronto in 1937, dedicated to promoting
and after completing medical school, moved to California excellence in research,
and then to Vancouver, where he became the founding Head education and training in
of Clinical Hematology in the Department of Medicine. Dr. benign hematology.
Naiman established the first Bone Marrow Transplant Center
at Vancouver General Hospital, and later became head of the
hematology laboratory at St. Paul’s Hospital until his retirement several years ago. His late wife, Dr. Linda
Vickars, was also a Clinical Professor in the Division of Hematology. She led the development of the first
comprehensive programs in hemophilia, hemoglobinopathies and hemosiderosis.
Together, this amazing couple provided a remarkably stimulating, motivating and highly academic
environment in hematology, devoted to delivering the best care for patients and their families. Shelly and Linda
were admired by all, and leave a wonderful legacy in their families, friends and all those whom they touched –
students, paramedical personnel, and professional peers.
Shelly and Linda were dedicated to promoting excellence in research, education and training in benign
hematology. They therefore created the Sheldon Naiman and Linda Vickars Hematology Endowment Fund at
the Centre for Blood Research, to which donations can be made. C

27

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