CBR
APRIL 2016
THE CENTRE FOR BLOOD RESEARCH
LET RARE MUTATIONS SPEAK ZIKA VIRUS NEW ANTIBIOTIC ENHANCER
PLUS UNDERSTANDING HOSPITAL INFECTIONS
ANTIOSTEOPOROSIS DRUG FROM HERBS
director’s note
Foundations for 2016
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I would like to thank everyone at the CBR, our partners, sponsors, collaborators, colleagues and friends for their ongoing commitment and support throughout the years. As we rapidly gear up for 2016, it’s worth reflecting on some of our accomplishments in 2015, which, from several vantage points, proved to be an exciting and a highly productive year.
Research emanating from the CBR continues to yield major breakthroughs in research into blood and blood-related products, many of which are poised for further development and application to meet clinical needs. To name but a few examples of advances made by CBR investigators in the last year:
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Transfusion medicine: • Identification of blood bag plasticizers that minimize adverse effects on stored blood products; • Delineation of mechanisms by which Dengue virus infects red blood cells and platelets; • Engineering of cell-surfaces using polymers to reduce inflammation; • Modification of polymers to reduce immunogenicity of transfused blood products; • Development of ultra-sensitive methods to diagnose leukemia.
Many of these discoveries have led to CBR investigators, Research Associates, PDFs, PhD students, MSc students, and undergrads receiving numerous prestigious awards and grants in 2015. Congratulations to all! 2015 also saw the CBR Summer Studentship program, with sponsorships from industry and private individuals, supporting a record number of 21 students. Students pursued their “hands-on” research projects, and participated in a variety of enrichment activities: from touring UBC facilities to discussing career options with our faculty and senior researchers. CBR’s annual Research Day further showcased the stellar CBR student performances with their outstanding oral and poster presentations. It also featured the first presentation of the Neil Mackenzie Mentorship Award that recognizes the mentors among us at the CBR. Nominated by his peers, the 2015 Award was presented to Steven Hur for his outstanding commitment to the mentorship of others and deep involvement in the effective running of his supervisor’s lab. The Earl Davie and Norman Bethune Symposia each drew record numbers of attendees (>180) in 2015, comprising clinicians, students, scientists, para-medical personnel and patient groups, drawn together to share new knowledge in the fields of bleeding and clotting disorders, inflammation/ infections and transfusion medicine. In
Hemostasis-thrombosis: • Development of self-propelling microparticles that can stop bleeding; • Introduction of personalized medicine approaches to prevent bleeding in patients with hemophilia; • Establishment of a Canadian network to study and improve outcomes from venous thromboembolic disease; • Initiation of studies to prevent thrombosis in patients with cancer. Inflammation/infection: • Improved understanding of mechanisms by which collagen degrades during aging; • Characterization of the proteome in dental pulp to provide insights into inflammatory gum disease; • Discovery of how the protein MALT1 controls the immune response and inflammation; 2
Description of the crystal structure of a sialyltransferase that participates in cellular functions relevant to cancer, inflammation and nerve regeneration; • Development of approaches to increase safety and efficacy of HIV therapy during pregnancy.
addition to participation by world-class speakers, we also added patient speakers, who presented personal accounts of living with related diseases. This simple innovation clearly was a moving one, placing so much that we do, in perspective. Save the date for the next Norman Bethune Symposium on April 12, 2016! In the past year, the CBR has also increased its commitment to support multiple grass-roots educational enhancements and opportunities for our trainees. In January, 2015, the Knowledge Translation (KT) Committee was conceived and then led by Education Program Manager, Anna Sinova. It has rapidly grown to 30 members, representing some remarkable and otherwise hidden, writing and science communication talent from our CBR labs. Over the year, they have published weekly articles, released monthly newsletters and quarterly publications. Their reach already exceeds 1000, comprising CBR members and alumni, colleagues in the life sciences industry, patients, and private and corporate donors. In 2016 the group is looking to expand into video journalism as a means to communicate the many fascinating stories of life at the CBR. They are always looking for new members!
The Career Development Program at the CBR gained momentum helping trainees develop career skills and establish meaningful links with industry and clinical partners. We saw a host of high quality workshops in scientific writing, journalism, entrepreneurship, transitioning into industry, résumé writing, and interviewing skills. In 2015, the CBR also hosted two Career Nights featuring representatives from Vancouver’s life sciences industry, providing ample opportunity for our CBR grads and PDFs to network in a low pressure environment. Having gained wide appeal, 2016 will see
PEOPLE
Antibiotic Enhancer Rare Mutations Hospital Infections
EVENTS
RESEARCH
06 07 08 10 11 02 18
AntiOsteoporosis
Iron Overload Foundations for 2016 Zika Virus
INTERVIEWS
Edward Conway, Director
APRIL 2016 ISSUE
NOTES
more of these career networking events, starting with the PDF Career Night on March 2. In 2016, expect new opportunities to tour life sciences companies, to further develop your career skills and to learn about the various career options available to the CBR graduates and alumni. The CBR annually funds highly competitive graduate students through the CBR Graduate Award Program, which is designed to enrich research training of students. In 2016, in addition to their regular mentorship program, journal clubs, and research presentations activities, the students are also planning their own miniSymposium. Stay tuned for the event details in June 2016! In 2015, the CBR introduced the “Blood Labs� Outreach Program, designed for high school students in the Vancouver area. Two groups of CBR graduate students delivered several fun, interactive and educational classes on DNA extraction and blood clotting to enthusiastic grade 9 and grade 11 science students. This highly successful program is a win-win for all involved, and will be expanded, as the teachers and students are eager for more. We would like to thank our many sponsors: UBC, the Faculty of Medicine, the LSI, the NaimanVickars Hematology Endowment Fund, and our many industry partners, for supporting our educational initiatives.
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Research Prize Curing Blindness Dentist Scientist Career Night Earl Davie Symposium Q&A Ed & Ed Food Bank 3
ABOUT CBR The CBR aims to improve the health and well-being of patients through innovative research in blood and bloodrelated processes.
GOALS CBR Research & Clinical Goals
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: Opportunity
Cost
Reward leadership in students and staff with the Neil Mackenzie Mentorship Award
$50
Expose trainees to diverse career opportunities with the CBR Career Night
$1,000
Jumpstart a postdoctoral fellow’s career with the Postdoctoral Transition Award
$5,000
Support a clinical fellow in Translational Research Studies
$75,000
Make a CBR Symposium possible
$25,000$100,000
Explore further: CBR.ubc.ca/support-us Edward M. Conway, MD, PhD Director, Centre for Blood Research Tel: 604.822.4252 | Email: ed.conway@ubc.ca
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• 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
E D U CAT I O N CBR Education Commitment • Support student research through competitive undergraduate, graduate, and postgraduate awards • Offer a range of stimulating educational symposia, workshops and seminars • Provide cutting-edge career development opportunities for our trainees
PEOPLE
CBR PUBLISHED BY Knowledge Translation Committee EDITOR-IN-CHIEF Anna Sinova DESIGNER Regan Zhang CONTRIBUTING EDITORS Abhinav Ajaykumar Andrew Alexander Georgina Butler Diana Canals Rolinda Carter Deb Chen Jenny Chik Tara Fernandez Anthony Hsieh Jenny Huang Michel Hughes Dustin King Theo Klein Prashant Kumar Victor Lei Bryan Lin Houra Loghmani-Khouzani Nima Khadem Mohtarem Preety Panwar Ido Refaeli Sara Saberi Erika Siren Nichollas Scott Solmaz Sobhanifar Shawna Stanwood Mike Trimble Olga Zamudio Regan Zhang BLOG cbr.ubc.ca FACEBOOK /cbrubc TWITTER @CBR_UBC CBR magazine is published by the 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 media communications. It is distributed 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 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 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 event coverage and CBR initiatives. If you are interested in participating in the KT Committee, email anna. sinova@ubc.ca or talk to one of the members! All grad students and PDFs are welcome to join.
Knowledge Translation Committee Science beyond academia CONTRIBUTE anna.sinova@ubc.ca
Awards Dr. Leonard Foster Receives UBC Killam Research Prize
From left to right: Queenie Chan, Dr. Marta Guarna, and Dr. Leonard Foster
D
r. Leonard Foster, Director of the Centre for High-Throughput Biology, and an Investigator with the Centre for Blood Research, has been awarded a highly prestigious UBC Killam Research Prize, recognizing his outstanding research and scholarly contributions. Prof. Foster was one of three recipients of the prize in the Applied Science, Sciences—Senior Category. The winners were selected by UBC’s Faculty Research Award Committee, which spans arts and humanities, business, education, applied science, science, and medicine. Each spring, the Office of the Vice President Research & International hosts an awards reception to recognize
outstanding UBC researchers. This year the reception was held on Wednesday, March 30, in the Robert H. Lee Alumni Centre. Dr. Foster’s research group focuses on using quantitative proteomics to study biological systems. They investigate a wide range of topics including pathogen invasion, infection, protein localization, and mapping protein interactions. One of his novel projects, extensively covered by the media, involves “using molecular diagnostics to selectively breed queen bees that are resistant to disease and produce more honey”—reported Metro News. C 5
RESEARCH
Potential Anti-Osteoporosis Drug P R E E T Y PA N WA R ,
Derived from a Traditional Medicinal Herb
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n a recent study published in the British Journal of Pharmacology, Dr. Dieter Bromme and his lab at the Centre for Blood Research (CBR), made an important discovery showing that it is possible to effectively prevent the loss of bone tissues in osteoporosis, while leaving other important molecular mechanisms untouched. Osteoporosis is a disease caused by weakening of the bones that affects the lives of millions of Canadians. It is a major burden to healthcare systems worldwide and increasing in prevalence as people live longer. Currently available drugs are far from ideal and long term treatment can lead to serious side effects. Recently, a protein called Cathepsin K has been identified as a novel target for the treatment of osteoporosis. The main role of this protein is the degradation of collagen during normal bone repair and rebuilding. During osteoporosis, this rebuilding process becomes poorly regulated and overactive, leading to a reduction in the strength of the bone. Several inhibitors of Cathepsin K are currently undergoing clinical trials, however they have been designed to block the entire functional region of the protein. Thus at least two trials have been halted as the drug appears
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Salvia miltiorrhiza
to be inhibiting other key activities of Cathepsin K and leading to significant side effects. Dr. Bromme and his team investigated whether there is a reduction in bone loss due to the action of DHT1, a non-active site binding inhibitor. Interestingly, DHT1 belongs to a large family of triterpenoids produced in Salvia miltiorrhiza or Red Sage, a herb used in the treatment of osteoporosis in traditional Chinese medicine. This inhibitor selectively blocks only the therapeutically relevant collagenase activity (breaking down of collagen) by Cathepsin K without interfering with other pathways. The unique advantage of DHT1 is that it only prevents the breakdown of bone, but does not interfere with its activity on other physiologically relevant non-bone proteins. This study demonstrates that by using the DHT1 inhibitor, it is possible to effectively prevent the loss of bone, while at the same time potentially reducing the side effects caused by alternative inhibitors. British Journal of Pharmacology, 173: 396–410.  C
RESEARCH
Surprising Findings DEB CHEN,
P H D C A N D I D AT E
New antibiotic enhancer has independent antimicrobial activity
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he discovery of antibiotics transformed patient care and dramatically advanced medical interventions and treatments. However, the relentless rise of antibiotic resistance over the years continues to threaten the diverse fields of medicine, including surgery, cancer chemotherapy, transplantation medicine and others. Recent PhD graduate, Dr Dustin King, from the Strynadka Lab at the CBR, discovered unexpected properties of the newly FDA-approved antibiotic enhancer, avibactam. The drug was expected to block the bacterial defenses against broad spectrum antibiotics. However, it was also found to have direct anti-microbial properties, making it the first such drug introduced to the market
within the last 30 years. Bacterial cells are unique from ours in that they have an essential cell wall structure, which is constructed of a massive net-like ‘peptidoglycan’ protective layer that envelops the entire cell. The synthesis of peptidoglycan involves penicillin-binding proteins, or PBPs, which were characterized through their affinity for penicillin. Penicillin, cephalosporins, and other related antibiotics share a similar core structure, the β-lactam ring, and thus are collectively referred to as β-lactam antibiotics. These are the most common types of antibiotics used in the clinics, for their potent ability to kill a broad range of bacteria. β-Lactam antibiotics are able to bind to the
PBP active site and irreversibly inactivate their function, which then interrupts the formation of the peptidoglycan layer. This subsequently leads to irregularities in the bacterial cell wall structure (e.g., elongation defects) and results in cell death. Over time, however, bacteria acquired the ability to produce protective enzymes, such as β-lactamases, which are able to break the β-lactam ring open and deactivate the drug’s antibacterial properties. Published in ACS Infectious Diseases, Dr. King and the research team in the Strynadka lab at the CBR, found that small amounts of avibactam and other diazabicyclooctane (DBO) derivatives were effective in inhibiting the growth of different multi-drug resistant Gram-negative clinical pathogens. This ability was independent of the presence of protective bacterial β-lactamases, suggesting that these drugs can act as direct antimicrobial agents. They further demonstrated that these DBO derivatives directly act on PBP to inhibit the synthesis of the peptidoglycan layer and to disrupt cell wall structure. The only such drug to be introduced into the clinic in over 30 years. “The diazabicyclooctane β-lactamase inhibitor constitutes the only such drug to be introduced into the clinic in over 30 years,” commented Dr. King. He is hopeful to play a part in the ongoing world-wide battle to “revive our current β-lactam [antibiotics] pool” through the development of novel β-lactamase inhibitor compounds. This finding is pivotal in the global effort to ensure public health and in finding new tools to design next generation pharmaceuticals with expanded spectra of activity against currently untreatable, antibiotic resistant pathogens. C 7
research
LET RARE MUTATIONS SPEAK
B cells communicate via cytokines with other inflammatory cells. Photo credit: F. Hoffmann-La Roche Ltd.
Novel Mechanisms in Immune System Regulation By Theo Klein, PDF
A collaboration between the labs of Chris Overall at the CBR, Stuart Turvey at the Child & Family Research Institute, and Mike Gold in I3 at the LSI, investigated a unique mutation in the MALT1 gene. This lead to a patient that paradoxically had a poor response to infection and autoimmune symptoms. The paper was recently published in Nature Communications and highlights the innovative proteomics research undertaken in the CBR to understand the actions of white blood cells. When B and T white blood cells recognize an antigen, a complex signaling cascade is set in motion that activates these immune cells and allows them to deal with an invading pathogen or cancer. However, if the response is too strong then autoimmunity can result. One of the key players in this cascade is MALT1, which acts like a pair of molecular scissors that inactivates inhibitors of the cascade, thereby boosting the activation of the immune cells. By comparing B cells from the patient with a mutated MALT1 gene, to the B cells from healthy family members, a new protein target for 8
MALT1 was discovered. It turns out that MALT1 also cuts a protein called HOIL1. Cleavage of HOIL1 stops other protein scaffolds, called linear ubiquitin, from being assembled and in turn dampens the immune response. The researchers already knew that MALT1 activity causes enhanced activation of the immune cells, but the discovery that it also acts as an inhibitor of the cascade was extremely surprising. This finding also partially explains the symptoms of the patient: failure to properly shut down B and T cell responses, leading to inflammation and autoimmunity, as well as poor immune response. Since MALT1 is under investigation as a potential drug target in treatment of certain types of lymphoma, these findings may be crucial in advancing further development of these compounds. Nature Communications, 6: 8777. C
people
SEEING T H E
L I G H T
Linnette Ocariza, a Masters Student in the Conway Lab, has a strong interest in age-related macular degeneration (AMD), the leading cause of vision loss among those over 50 in developed countries. BY TARA FERNANDEZ, PDF Losing the ability to see a loved one’s face clearly, or use a computer or cell phone is probably unthinkable to most of us. However, this is the frightening reality for those suffering from age-related macular degeneration (AMD), the leading cause of vision loss among those over 50 in developed countries. This progressive degenerative disease of the eye affects about 8 million individuals in the United States alone and has a devastating effect on the quality of life for most sufferers. The macula is the most sensitive region of the retina, consisting of specialized cells required for high-definition central vision. Damage to the macula results in distortions or darkened patches appearing within the central field of view. This makes everyday activities frustratingly impossible. To make matters worse, very little is known about the pathophysiology of AMD, with suitable treatments only available for people with a small sub-type of this condition. Interestingly, excess complement activation and oxidative stress have been identified as potential mechanisms underlying this disease. Linnette Ocariza, a Masters Student in the Conway Lab, has a strong interest in the molecular regulators of the complement system and has spent the last 2 years uncovering more about their role in AMD progression. As part of her research, together with others in the Conway Lab, Linnette discovered a fascinating association between AMD and a molecule found in bacteria and commonly used as a food preservative, which may hold the key to arresting the progression of the disease. Polyphosphate (PolyP) is an inorganic polymer that has been in the spotlight due to its potent inhibitory effects on the complement system. Abundantly found in platelets, PolyP has been shown to modulate several aspects of coagulation and inflammation. As a naturally occurring compound, PolyP is therefore a promising candidate for combating AMD, by suppressing the immune system and limiting damage to the eye by oxidative stress. Linnette tested this theory in a variety of cell and mouse experimental models.
These included a state-of-the-art technique she learned for creating controlled lesions on the retinas of mice in order to simulate AMD damage and identify the effects of potential remedies. She found that PolyP not only significantly interfered with the terminal pathway of complement, but also acted as an antioxidant, thus dampening the main routes of AMD progression. Looking back on the highs and lows of her Masters experience, Linnette spoke on some of the challenges and victories associated with her research. Long hours and failed experiments paid off after making some important breakthroughs in her work, particularly with her in vivo studies. She strongly believed that being part of a supportive team and engaging with the wider CBR community helped her to grow as a researcher and learn from the experiences of her peers. Being given the opportunity to mentor Summer Students, present at CBR seminars and travel to conferences have also equipped her with valuable academic and life skills for the future. Eager to pursue a career in Medicine, Linnette has the following advice for the next generation of researchers – be resilient and patient; and get involved with scientific activities outside the lab. She is hopeful that her discovery may one day lead to a ray of hope for those battling AMD by providing them with a safe and effective treatment for their disease. C
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research
KILLING US WITH
SWEETNESS BY NICHOLLAS SCOTT, ALUMNUS
Acinetobacter baumannii is an emerging opportunistic pathogen of significant concern to health care institutions worldwide. Since the 1970s, drug resistance and the ability of this pathogen to survive in harsh environments has led to an increased frequency of high-risk outbreaks in burn and intensive care hospital units. Within these settings, A. baumannii infections cause ventilator-associated pneumonia and wound infections, leading to life-threatening bacteremia/sepsis, especially in immunocompromised populations. Therefore, understanding the mechanisms by which A. baumannii resist the host’s immunological response could go a long way towards preventing further outbreaks in the hospital setting. The survival of A. baumannii within the host’s blood is largely mediated by the generation of different polysaccharides, which coat the bacterial surface and create a dense protective capsule. These capsule structures confer A. baumannii with resistance to complementmediated killing, allowing replication within the bloodstream and long-term survival on abiotic surfaces. Although in many bacteria, the carbohydrates are exclusively used for capsule generation, within A. baumannii, the capsule monomer can also be conjugated to protein substrates in a process known as protein glycosylation. Through collaborations between the Foster lab at the CBR and the Feldman lab at the University of Alberta, we were able to characterize the biosynthetic pathways involved in protein glycosylation in A. baumannii bacteria. These pathways are highly conserved and essential for biofilm formation and virulence. Our findings demonstrated that a functional glycosylation system is required for virulence in A. baumannii bacteria. However, the specific role of protein glycosylation in A.
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A. baumannii—helium ion microscopy. Image from: miphidic.wordpress.com
Dr. Nichollas Scott was a postdoctoral fellow at the lab of Dr. Leonard Foster (2012-2015), and has recently returned to Australia to begin a senior postdoctoral fellow position at the University of Melbourne. Nichollas is a fellow with the National Medical Council Australia CJ Martin and Michael Smith, specializing in the application of proteomic tools to study protein modifications and interactions. Through the support of a CBR Transition Grant, Nichollas began an independent research program on bacterial glycosylation, aiming to investigate its potential as a drug target.
baumannii is still unknown, as there is no known mechanism currently linking glycosylations to pathogenesis. The CBR Transition Grant provided me with a unique opportunity to collect some of the initial data needed to begin an independent research project. In my new position at the University of Melbourne, I am continuing my work on the role of protein glycosylation in bacterial pathogens. I have further expanded these projects to investigate the recently identified glycosylation systems of Burkholderia cenocepacia bacteria and the glycosyltransferase toxin utilized by multiple pathogens. The ability to obtain these initial data and take the first step towards establishing my independent research program would not have been possible without the aid of the CBR transition grant. Molecular & Cellular Proteomics, 13(9): 2354–2370. C
research
IRON OVERLOAD REDUCTION IMPROVES QUALITY OF LIFE By Regan Zhang, PhD Candidate
Eight years ago, John didn’t think he could live much longer, as his anemia was progressively worsening. Doctors had given him the diagnosis of myelodysplastic syndrome (MDS), a condition which leads to the decline of blood-producing bone marrow cells. Consequently, he needed red blood cell transfusions regularly in order to maintain his red blood cell count. Red blood cells are essential to carry oxygen to the tissues. Over the last two years, John has been transfused with 80 units (bags) of red blood cells, which has caused another problem. His iron levels became significantly elevated. Iron overload is a major side-effect of blood transfusions, says Dr Heather Leitch, hematologist at St. Paul’s Hospital and Centre for Blood Research, University of British Columbia. Excessive iron is toxic to many organs, and thus may result in liver disease, heart disease, and diabetes. The major remedy for iron overload is iron chelation therapy, which uses drugs to capture excess iron and remove it safely from the body. Luckily for John, the highly effective oral chelation drug, deferasirox, a convenient formulation, has become accessible for patients with MDS. After just six weeks of treatment, not only did his iron levels drop, but astonishingly, John’s regular blood transfusions were no longer needed. His iron levels entirely normalized over the following months and remained normal, particularly as his need for transfusions were substantially reduced. In a recent review article published in the journal Canadian Perspectives in Clinical Hematology, Dr
Leitch describes a number of studies that report that iron chelation therapy may be beneficial for patients with MDS. In addition to being toxic to the heart, the liver, and the pancreas, Dr Leitch points out that, due to the damaging effects of iron on DNA, iron overload may also increase the risk of progression to leukemia. Through active management of iron overload, the risks of blood transfusions can be significantly reduced. On an even more promising note, one study found that the longer that patients with MDS received iron chelation therapy, the higher the chance there was of them becoming transfusion independent, sometimes for long periods. The biological reason for this surprising improvement in the MDS is still being investigated. Dr Leitch indicated that more has to be done to fully understand the mechanisms of this treatment, noting that “iron reduction is in some way favorably altering bone marrow failure”. As guidelines for iron chelation treatment are still in the process of being updated in many jurisdictions, Dr Leitch believes that removing iron should be pursued as an active treatment for patients receiving blood transfusions for bone marrow failure syndromes. Iron overload might be improved not only by iron chelators, but by other treatments for bone marrow failure syndromes that reduce transfusion requirements. Thus, iron reduction can have a significant impact on the quality of life and long term well-being of patients like John. C 11
people
DENTIST WITH A LAB COAT On a cold Monday morning, nearly a million health-care providers in Canada are going to see patients. A small number of them, less than one in 200, also work as a scientist. The clinician-scientist is one of the most educated professionals; the average clinician-scientist holds three to four degrees after a lengthy training process that takes well over a decade to complete.
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By Regan Zhang, PhD Candidate
Many in the medical field understand that there is a gap between medical research and clinical practice, where scientific knowledge doesn’t flow very well from the laboratory to the bedside, and vice versa. The value of a clinician-scientist lies in that unique position between these two worlds. Having a breadth of knowledge from both sides, makes them the key players in translating research results into clinical practice, and developing research questions based on clinical issues. Although this profession declined significantly in the 1980s and 1990s, the Canadian Institutes of Health Research rolled out programs at the turn of the century aimed at reducing barriers in order to train more clinician-scientists in Canada. Dr. Hugh Kim of the Centre for Blood Research is one of the newest clinician-scientists in British Columbia. Trained in dentistry at the Université de Montréal, and periodontics at The University of British Columbia, Dr. Kim benefitted from being in a basic research laboratory early in his career, a rare opportunity for most dentistry graduates. He completed his PhD at the University of Toronto, before coming back to UBC as a researcher. Dr. Kim, a specialist in gum disease that affects almost half of the adult population, sees patients every week in his clinic. But in the lab, he doesn’t look at people’s gums. Instead, he studies the one trillion platelets in the human body. As Dr. Kim became interested in chronic inflammation, which is a central feature of the gum disease he observes in patients, he realized that the platelet is an important cell in this system. Platelets have a well-established role in blood clotting, but now scientists are recognizing their important contribution to inflammation. “Platelets are an abundant source of signalling molecules that are essential for normal immunity and wound healing,” says Dr. Kim. With new funding from the Canada Foundation for Innovation (CFI) and the BC Knowledge Development Fund (BCKDF), and a lab composed of students and a postdoctoral fellow, Dr. Kim’s team is focused on identifying the mechanism of how platelets interact with their surroundings and modulate inflammatory diseases. In particular, the lab is unravelling the role of the cell’s structural framework and its component proteins in relaying messages to the surrounding tissues. Chronic inflammation is a key mechanism that contributes to a multitude of diseases, and for Dr. Kim, this research is certainly important for gum infection. But understanding the science of platelets goes far beyond. C
events
IDEAS LEARNED at CBR Postdoctoral Career Night BY HOURA LOGHMANI-KHOUZANI, PDF Every year the numbers of life sciences PhD graduates rise and many continue onto postdoctoral training, becoming an important pillar driving scientific progress. However, the long academic training often does not lead to secure jobs in academia, as the number of full-time faculty positions around the world have plateaued and even shrunk in the last 10 years. Therefore, careers in industry and other non-academic environments are becoming more common for postdoctoral fellows, and with creativity and exposure, a wide range of jobs to choose from can become available to them. The Centre for Blood Research at UBC aims to help, organizing their bi-annual Postdoctoral Fellows Career Night event. It was held on March 2, 2016 and was cohosted by the Postdoctoral Fellows Office and the Department of Microbiology & Immunology. The event was open to all UBC postdocs, drawing 60-plus attendees. Eighteen excellent mentors participated to answer questions, and impart tips and advice for the postdoctoral fellows. Among them, you could have found big data and bioinformatics specialists, policy makers, R&D engineers, environmental planners, college instructors, business development specialists, product specialists, entrepreneurs, scientific writers and intellectual property experts. The night started with three 20 minute sessions, where participants had table discussions in small groups with their chosen mentors. This was followed by a delicious wine and cheese networking event, which allowed the conversations to continue, further building relationships among the mentors and the postdocs. Additional well-positioned academic mentors joined the group to mingle. A common theme of the night was to
find your own way by making the most of your strengths, combined with a mindset of flexibility and growth. Neither staying in academia nor moving to industry, Dr. Geraldine Walsh found her own way and pursued her career as a scientific writer, currently working at the Canadian Blood Services’ Centre for Innovation. She was a postdoctoral fellow at the Biomedical Research Centre at UBC before realizing that her real passion was writing. Since 2010 she has been working as a scientific writer and editor. When asking her for a good starting point in a writing career she agreed that writing your own blog, or participating in volunteering activities that involve outreach and communication, can help grow writing skills and hone in on key interests and topics. One of the most energetic and enthusiastic mentors, Dr. Grace Lee, who is a neuroscientist, public speaker, marketing strategist, food blogger, and entrepreneur, shared her own way of building on strengths and interests. Frustrated with the academic system, Dr. Lee became engaged in e-commerce with her own marketing business and later accepted a management position in STEMCELL Technologies Inc. She believes that in order to be successful you should transform your passion to an idea and then your idea to business. A good way to get hired is to show that you are able to identify the company’s problem and to take it on with creative solutions. There is a common believe that having a certificate in MBA will help you to find better jobs and opportunities, but Dr. Rhonda Wideman who works as the Manager of External R&D and Alliances at Zymeworks, thinks that getting a certificate in Project Management is as valuable, while being less
expensive. She also advised the PDFs to start working for smaller startup companies, where there is more possibility of lateral growth and success. Her tip for writing resumes was to demonstrate flexibility and broad knowledge and expertise. Flexibility and networking represent key ingredients when transitioning to a new career. Dr. Naomi Galinski, now a 3rd tier technical support specialist at the software company Copperleaf, after obtaining a PhD in astrophysics, mentioned that her new employers declared to her they were looking for “CPUs and not memory” candidates. She recommends young graduates to openly approach potential companies and careers they are interested in, with the knowledge of how their PhD experience can be translated in a different field. Finally, Dr. Carol Friedrich-Fong, former PDF at the Center for Blood Research, now Program Head and an instructor of Biotechnology and Molecular Genetics in the UBC-BCIT joint Biotechnology program, also recommends graduates to identify their key strengths before commencing to apply for new jobs and consider how those strengths can match the type of job they are seeking. Reflecting on and knowing your value can help identify interesting and satisfying job opportunities. Overall, the CBR Career Night and other similar events provide a perfect networking environment for the job-seeking PDFs. This is a place not only to find mentors, but also to meet fellow PDFs and make lasting connections. After all, your next career may start right here! C 13
events
BY KT COMMITTEE JOURNALIST TEAM
EARL W. DAVIE SYMPOSIUM 2015
Dr Earl Davie (centre left) with symposium speakers
Dr. Earl W. Davie’s illustrious research career has spanned over four decades and revolutionized treatment options for hemophilia patients. Together with his colleagues, he characterized the ‘Waterfall Sequence’: the molecular cascades involved in the formation of the fibrin clot. To honor this distinguished investigator, the CBR hosts the annual Earl Davie Symposium, showcasing endeavors in the fields of vascular biology, hemostasisthrombosis, cardiovascular and neurologic disease, by both local and international experts. The 9th annual symposium was held at the SFU Harbour Centre downtown, which treated attendees to sweeping waterfront views of Vancouver. Keynote presenter Dr. Kenneth Kaushansky from Stony Brook University began the day’s proceedings with an engaging talk on thrombopoiesis. He discussed recent therapeutic advancements and discoveries in the field, including collaborations with his daughter on various projects. Dr. Gayatri Sreenivasan, the Medical Director of the VGH Apheresis Program, then highlighted the importance of the early diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP). Once diagnosed, the mortality rates of patients with TTP can shift dramatically from 90% to under 10% using plasma exchange. 14
During her poignant talk, TTP-survivor Mina Rajan shared the emotional and physical challenges of life with TTP, crediting her recovery to the ongoing support of the Answering TTP foundation. Speaking with Mina after her talk, she remarked that she was overwhelmed by all of the interest and inspiration she received from the symposium attendees. She was taken aback by the passion and dedication of CBR researchers for their work, along with their earnest desire to improve the lives of patients like herself. The morning session concluded with short talks from Drs. Junmei Chen and Linda Sun, both who presented research which provided insight into von Willebrand Disease. During the delicious lunch spread, we were fortunate to be able to sit down with Dr. Davie himself, together with Nobel Prize winner,
Dr. Eddy Fischer. Both Earl and Eddy spoke candidly about their struggles and highlights during their careers. It was immediately apparent that their success could largely be attributed to their genuine zest for the scientific process, a deep curiosity about the unknown and a witty sense of humor. Eddy in particular had some sage advice for the next generation of scientists, encouraging them to ‘always be prepared for the unexpected’. He shared that from personal experience, many of his greatest scientific revelations had been completely serendipitous. Therefore, we are advised to keep an open mind and be prepared to pursue tangents that catch our interest. Earl also stressed the importance of working in a collaborative environment and embracing emerging technologies as alternatives to more traditional techniques. It was clear that neither Eddy nor Earl were showing any signs of settling down and remain very keen on staying connected with the vibrant scientific community. The Poster Session featured the fascinating and diverse projects by CBR’s own students, postdoctoral fellows and researchers. The high-quality poster presentations were extremely well-received, serving as a platform for many engaging conversations. Out of all the sterling research posters presented the best poster prize was ultimately awarded to Abhinav Ajaykumar, a third-year PhD student in Dr. Hélène Côté’s lab. His poster, titled “Timing and type of maternal combinations anti-retroviral therapy modulates placental telomere length and mitochondrial DNA levels” highlights his
Abhinav Ajaykumar, winner of the best poster prize
The Poster Session featured diverse projects by students, postdoctoral fellows and researchers research progress in unravelling how antiHIV drugs affect cellular aging. Abhinav thanked the encouragement from his fellow lab members, as well as the organizers and volunteers of the symposium. In the future, Abhinav plans to use his PhD training as a platform to enter the public health industry. The afternoon session commenced with a keynote talk by Dr. Bjorn Dahlback, on novel insights into the dual role of Factor V (FV) as both a coagulant and anti-coagulant. He detailed the fascinating activation mechanisms and synergistic interactions between FV and Protein C. Dr. Susan Smyth, from the University of Kentucky, presented her recent discoveries on the development and progression of atherosclerosis. Dr. Smyth showed compelling data that elucidates the role of the protein PPA2B in suppressing atherosclerotic inflammation. This year, the symposium offered the opportunity for CBR affiliated members to present their research alongside the invited speakers. Stefanie Novakowski started things off detailing her impressive work which utilizes platelets as drug delivery vehicles. Dr. Peter Schubert educated the audience on advances in platelet storage technology. Representing Dr. Hongshen Ma’s research group, PhD candidate Aline Santoso also presented her findings. A student in the Department of Mechanical Engineering, Ms. Santoso explained how microfluidic technology can be used to sort and characterize red blood cells in a simple high throughput manner. While the selected members represented very different fields
of research, all displayed new and improved ways of handling blood components. In the final set of presentations, Dr. Douglas Cines from the University of Pennsylvania reported his work on the therapeutic delivery of plasminogen activators and the pathogenesis of heparin-induced thrombocytopenia. Dr. Braedon McDonald concluded the day’s proceedings with some stunning examples of technological advances in in vivo imaging and intravital microscopy techniques to study platelet activation and coagulation during infection. Dr. McDonald illustrated his exceptional work on elegantly mapping the interactions between neutrophil extracellular traps and pathogens, as well as the deposition of fibrin during systemic infections. Director of the CBR, Dr. Ed Conway, expressed his gratitude towards the participation and contributions of presenters and the audience alike, especially for the stimulating discussions during the Q&A sessions. He was delighted for yet another hugely successful symposium, and for the attendance of the guest of honor, Dr. Earl Davie himself. Ed also acknowledged all the hard work put in behind the scenes in preparation for the event and the support from Associate CBR Director, Ed Pryzdial, as well as Hana Kim and Anna Sinova. Reflecting on the exciting breakthroughs in the field of blood research presented at the symposium, CBR members could not hide their enthusiasm for their projects and anticipation for next year’s symposium. C 15
INTERVIEWS
Q & A with Ed & Ed Last week, a budding reporter and Conway Lab Manager, Victor Lei sat down with CBR’s Director Ed Conway and CBR Associate Director Ed Pryzdial to talk about the 9th annual Earl Davie Symposium.
to them. EC: Also, seeing students so engaged and being exposed to so many great, successful scientists is definitely a highlight. Just seeing clinicians and scientists connecting, discussing and brainstorming. This is a great opportunity to get people together, especially over wine and cheese! VL: What are some things that people might not know about making the Earl Davie Symposium a success? EC: Well, we had one speaker unfortunately fall ill only 4 days before being scheduled to speak. So, as you can imagine, it was quite a rush to find a replacement! EP: It can be difficult getting experts to take time out of their hectic schedules to spend the day with us. Usually, they immediately agree as soon as they hear that Earl himself would be present in the audience!
VL: What did you think of this year’s event? EC: It’s been a huge success. We have had the best lineup of expert speakers to date! EP: The quality of the talks was excellent. It was one of the most highpowered and amazing group of speakers in the field. VL: What were some of the highlights of the day for you? EP: Braeden McDonald dazzled us all with color and insight that was fantastic. Also, it was heartwarming to see a 95-year old Nobel Prize winner, Eddy Fischer, asking a question after a presentation. EC: Definitely the chance to spend time with our guest of honor, Earl Davie. He is a living legend and it’s always such a pleasure to talk with him. We are really lucky to have him just a couple of hours away in Seattle. EP: Absolutely. Both Earl and Eddy are world class scholars and so gracious to spend the day with us. It is always encouraging and motivating to speak
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VL: What are your thoughts about future Earl Davie Symposiums? What would you like to see? EP: Definitely more of Eddy Fischer. His mind is such a fertile garden, he is incredibly creative. Once, we sat at a café together and compiled a list of reasons validating the existence of unicorns. We are in the process of publishing this work. EC: Yes, we would love to see our fantastic VIPs again and for them to share their wisdom with us. VL: Finally, if you could imagine yourself as a major component of the coagulation cascade, which one would you be? EC: The C5 convertase… EP: ….I can’t give you an answer, I’d be too biased! C
interviews
FO O D BA N K
The UBC Food Bank is located in the lower level of the Old SUB building (Room 42U). For tips on making your food dollar stretch and more details about the Food Bank (including the bank’s hours and policies) see the UBC Food Bank Blog. Look for the food “donation station” boxes set up in the LSI lunchroom (Level 4)—including one in the refrigerator for perishable items. All donations will go to the UBC Food Bank. If you are interested in helping promote food donations and collections please contact the author at mhughes@brc.ubc.ca. The Centre for Blood Research (CBR) reminds the reader that the UBC Food Bank is one of many important causes in need of financial and volunteer support.
BY MIKE HUGHES, RESEARCH ASSOCIATE
The UBC Food Bank has Your Back If judged on my current figure, you would probably be surprised to know that I skipped a few meals when I was a graduate student. With weeks to go until my next NSERC installment, my bank account was in overdraft protection. The poor, “starving” graduate student trope is not just a cliché. Fortunately, I had a good support system and parents who were able to help out when I needed a boost. I’ll always be grateful for those timely grocery gift cards. Not everyone is so lucky—so what do they do? The UBC student society maintains a Food Bank for the exclusive use of UBC undergraduate and graduate students and students attending colleges affiliated with UBC (you just need a valid UBC student ID). The coordinator of the Food Bank, Jay Singh (foodbank@ams. ubc.ca), says that the program has experienced a dramatic increase in clients in the last 12 months, a need that has fortunately been met with an increase in donations to the bank. I spoke with Jay recently about the UBC Food Bank’s goals for 2016 (the following is a paraphrased summary).
Q: What are your most important goals for the Food Bank in the next year? Jay: We are always concerned with making sure we continue to get donations to a level that matches our clients. But this year we will also have a major focus on getting the word out…making sure that UBC students, our clients, know that we exist. Q: Can you tell me about your typical clientele? Jay: There isn’t really anything that is typical. Many of our clients are usually feeling at a low point in their lives but I am working hard to eliminate any stigma associated with using the Food Bank. Everybody has ups and downs in their lives and when they have a need to use the Food Bank, we want them to know that we are here to help. It shouldn’t be a big deal – many people struggle to make ends meet, especially students. You may need a bit of help one day, but you may be donating the next. Our motto is “We’ve got your back”. Q: What about volunteers – do you have sufficient help to run the Food Bank? Jay: We have several highly dedicated volunteers who work at the Food Bank, stocking the shelves, interacting with clients and promoting the Food Bank to donors and potential clients. In terms of new volunteers, we need people who can bring their own initiative to the table. We want people to think about what they can do for the Food Bank, to bring in more donations and execute the work themselves – that has the greatest impact. Q: What type of food do you generally need for donations? Jay: I tell people to donate high quality foods that they would eat themselves. Non-perishable foods are preferred but we do have a refrigerator and plan to get a chest freezer soon. This will allow us to provide more fruits and vegetables and some perishable frozen goods. C
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NOTES
Zika ANTHONY HSIEH,
P H D C A N D I D AT E
The Spread of Zika Virus through the Americas and the Shield of Canadian Winter
T
he mosquito-borne Zika virus (ZIKV) was first introduced to the Americas in Bahia, a Brazilian state best known for 1000 km of postcard-worthy beaches sporting coconut palms and hot sun. It began in late 2014, when patients with acute exanthematous (skin rash) symptoms began appearing throughout northeast Brazil. In March 2015, the origin of this illness was identified as ZIKV in Bahia and northeast Brazilian state Rio Grande do Norte. Over the past year, the infection has spread to almost all Western hemisphere countries south of and including Mexico. ZIKV is known in international popular media for its association with microcephaly (abnormally small head), a neurological disorder in newborn babies. In October 2015, increased rates of microcephaly were detected in the state of Pernambuco, Brazil, which appeared to be connected with the Zika outbreak. This prompted an investigation that identified a sweeping surge of microcephaly diagnoses in several Brazilian states compared to previous years. In November, the Brazilian Ministry of Health declared a public health emergency
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in response to the increased number of microcephaly cases. Since October 2015, 583 cases of microcephaly had been confirmed in Brazil, up from an average of 150-200 per year between 2010 and 2014. In February 2016, the WHO announced a Public Health Emergency of International Concern to address the association between ZIKV and neurologic disorders such as microcephaly. ZIKV was first detected in a rhesus monkey in Zika Forest, Uganda in 1947. Since then and prior to its spread to the Americas, circulating virus had been found in tropical regions of Africa, Asia, and the Pacific islands. In fact, a genetic study of the virus indicates that it spread into Brazil via French Polynesia. The virus is carried by various mosquito species of the Aedes genus, primarily Aedes aegypti, a species responsible for transmitting viruses closely related to ZIKV such as Dengue, Yellow Fever, and West Nile. Unlike the climate in balmy Bahia and most of the Americas (including the US),
the frosty Canadian winter prevents establishment of Aedes aegypti breeding populations. Despite the aegis of Canadian frigid air, suspected cases of ZIKV spreading through blood transfusions have been reported in Brazil and French Polynesia. These cases are difficult to confirm due to both regions being endemic to ZIKV at the time of the report. As a precaution, Canadian Blood Services (CBS) has implemented a 21-day waiting period for blood donors who have travelled outside Canada, the continental United States, or Europe. After 21 days, the virus is cleared from the bloodstream. The Chief Medical and Science Officer of CBS, Dr. Dana Devine, describes the waiting period as “more than adequate”, taking into account suspected cases of infection through blood transfusion in endemic countries. She reminds donors to give blood before they travel. The Public Health Agency of Canada (PHAC) recommends that travellers protect themselves from mosquito bites, and asks pregnant women (or those considering becoming pregnant) to think about postponing travel to ZIKV-affected countries. Travellers returning from affected areas to Canada and the US have brought ZIKV back, with 14 cases of infected Canadian travelers reported as of Feb 25, 2016. However, there have been no reports of local transmission of the virus in Canada. In the US, there are a growing number of cases of suspected sexual transmission,
where infections occurred in non-traveller females (including pregnant women) who have had sexual contact with male partners returning from an affected country. Of the 9 pregnant women in the US with ZIKV, 1 infant was born with severe microcephaly. Dr. Devine, who is also a principal investigator at the CBR, believes that the current most pressing issue is to establish the true risk of ZIKV to pregnant women. There remains a need to determine whether the link between ZIKV and microcephaly in newborns is associative or causative. Although ZIKV presents a greater threat against our Southern neighbours, Canadian researchers are prepared to proactively study this virus. Dr. Robbin Lindsay at the National Microbiology Laboratory in Winnipeg and Dr. Fiona Hunter at Brock University in Ontario have started investigating whether mosquito species that are able to breed in cold Canadian winters are able to carry and transmit ZIKV. The rising temperatures of the coming seasons may crack the icy shield that has so far prevented the most common ZIKVtransmitting mosquitos from crossing our borders. As for scientists at the CBR, Dr. Devine believes that researchers here have the expertise to determine “whether the technologies that are available to essentially sterilize blood products actually kill Zika virus.” This would not only help in the event that ZIKVcarrying mosquitos invade, but would also contribute to the global fight against this pandemic. C
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