Li Ka Shing Institute of Virology Annual Report 2018

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2018 Annual Report Li Ka Shing Institute of Virology University of Alberta


. InScope is located in front of the Li Ka Shing Centre for Health Research Innovation (corner of th th 87 Avenue and 112 Street). This piece was commissioned as part of a transformative gift from the Li Ka Shing (Canada) Foundation to the University of Alberta in 2010. InScope, 2015 Dam de Nogales University of Alberta Art Collection (2015.7.1) University of Alberta Museums Photo Credit: Christy Dean Photo (christydean.com) Š Li Ka Shing Institute of Virology

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


TABLE OF CONTENTS Li Ka Shing Institute of Virology (LKSIoV) Message from the LKSIoV Director, Dr. D. Lorne Tyrrell…………….

1

Vision and Mission Statements.………………….……………………..

1

Highlight: 2018 LKSIoV Translational Research Symposium………..

2

2018 at-a-Glance……………….…….………………..…………………

3

LKSIoV Funding…………………………….……………………………

4

LKSIoV Team………………………………………………..…………..

5

LKSIoV Governance…………………………….…..…………………..

6

LKSIoV Membership………………………………………..…………..

7

Our Impact…………………………………………..……………………

13

Statement of Operations………….…………………...………………..

14

Accolades……………………………………………………………..….

15

Li Ka Shing Applied Virology Institute (AVI)

17

Message from the Director, Dr. Michael Houghton……….………...

18

AVI at-a-Glance…………………………………………………………

20

AVI-Incubated Projects….……………………………….…………….

21

AVI Team……….………………………………………….……………

23

AVI Funding Sources………………………………...………………...

28

LKSIoV & AVI Partnerships & Collaborations………………………………………...

29

Contact Information………………………………...……..…………...

32

2018 Li Ka Shing Institute of Virology Annual Report


MESSAGE FROM THE FOUNDING DIRECTOR DR. D. LORNE TYRRELL Making profound and positive impacts on the health of people around the world requires talented researchers and novel ideas. Since its inception, The Li Ka Shing Institute of Virology (LKSIoV) has continuously invested in virology, immunology and other types of research to discover new methods to prevent, treat & cure virus-related disease to reduce the burden of viral disease around the world - 2018 was no exception. According to the World Health Organization, 5 out of the 10 threats to global health are viral in nature, with viruses indirectly implicated in the other threats as well. The ten threats are: air pollution and climate change, noncommunicable diseases, global influenza pandemic, fragile and vulnerable settings, antimicrobial resistance, Ebola and other high-threat pathogens, weak primary healthcare, vaccine hesitancy, Dengue, and HIV. Fragile and vulnerable settings have an indirect viral association, given the commonality of HBV and HCV amongst vulnerable populations around the world. Additionally, climate change can result in the spread of viral illnesses such as Zika and West Nile virus, as well as other tropical diseases like Malaria, as rising temperatures push disease-carrying mosquitoes into new places, including North America. The work in the Institute is directed at developing vaccines, improving target-specific therapies, and understanding pathogenesis. The information in this annual report will provide you with an insight to our collective progress. These research innovations pioneered by our membership would not be possible without the generosity of the Li Ka Shing (Canada) Foundation, as well as financial support of key partners, such as the Government of Alberta, GlaxoSmithKline, and private donors. 2018 was a year of great achievements and positive change for the LKSIoV: • The Management Review & Advisory Committee was re-established in May; • Operations & Research Manager, Dr. Carla Craveiro Salvado, joined our team in July; • Our new and interactive website was launched in September, housing up-to-date information for all stakeholders and interested persons; • Our Trainee Education Programs portfolio was re-vamped and launched in August, with awards for trainee travel, entrance scholarships, as well as several matching partnerships with the Faculty of Medicine & Dentistry, as well the Department of Medical Microbiology & Immunology; • The Research Support & Innovation Grants program was also updated and launched in December, offering semiannual competitions; • The LKSIoV Translational Research Symposium, a showcase of translational research & commercialization projects supported by the LKSIoV and LKSAVI respectively, was held on November 28; • The AVI made great strides in a number of its incubated projects. The LKSIoV strives to enhance student experiences by supporting the various programs within our portfolio, as well as support the research environment with acquisition of leading-edge equipment and research awards. Together with our current and potential partnerships, as well as valuable members and their respective trainees, we will continue to endeavor for a world with reduced viral and other infectious disease burdens. Dr. D. Lorne Tyrrell, OC, AOE, MD, PhD

VISION Leading the world in virology discoveries and cures. MISSION Through leadership in scientific excellence & international collaboration, the LKSIoV will invest in virology & immunology research to discover new methods to prevent, treat & cure virus-related disease to reduce the burden of viral disease around the world. Li Ka Shing Institute of Virology • www.uab.ca/lksiov


2018 HIGHLIGHT 2018 LKSIoV Translational Research Symposium – November 28, 2018 The LKSIoV Translational Research Symposium was held on Wednesday, November 28, 2018. The focus of this day was to showcase all of the exemplary translational research projects supported by the LKSIoV, as well as highlight the commercialization opportunities incubated by the Li Ka Shing Applied Virology Institute (LKSAVI).

Dr. D. Lorne Tyrrell (Founding Director, LKSIoV) delivering the welcome address at the 2018 LKSIoV Translational Research Symposium held on November 28, 2018.

LKSAVI-incubated projects presented by the respective program leader (or representative) included:    

Dr. Michael Houghton - A Hepatitis C vaccine: Benefits to Alberta and Canada Dr. Gregory Tyrrell - Development of a Vaccine to Prevent Streptococcal Skin and Invasive Disease Dr. David Evans - UAB-211: An Oncolytic Vaccinia Virus for Treating Early-stage Bladder Cancer Dr. Jack Jhamandas - A Novel Therapy against Alzheimer’s Disease

  

Dr. Amir Landi - New Biomarkers for Autoimmune Hepatitis Dr. James Nieman - Human Cytomegalovirus Antiviral Program Dr. Khaled Barakat - Developing Small Molecule Inhibitors For The Immune Checkpoints

Since inception, the LKSIoV has supported its members through funding of various research initiatives. The various LKSIoV-funded projects presented at the Translational Research Symposium included:  

  

 

Dr. Troy Baldwin - Regulation of Nur77 Transcriptional Activity for Therapeutic Purposes Dr. Stephanie Yanow - Mapping a Cross-species Epitope as a Vaccine Candidate against Placental Malaria Dr. Tom Hobman - RNA Virus-host Interactions at the Cellular Level: In Search of Novel Antiviral Targets Dr. Maya Shmulevitz - Reshaping Reovirus for the Tumor Niche Dr. Michael Hawkes - A Humanized Mouse Model to Study Cell-Mediated Immune Responses to LiverStage Malaria Vaccines Dr. Katharine Magor - Generation of InfluenzaResistant Chickens Expressing Duck RIG-I Dr. Jim Smiley - Does Herpes Simplex Virus “Deliberately” Activate the cGAS/STING Antiviral Pathway in Human Cells?

  

  

Dr. Andrew Mason - Human Betaretrovirus Infection in Autoimmune Liver Disease Dr. Kevin Kane - High Throughput “CTLArray” for Antigen Identification Mr. Cameron Griffiths - Inhibition of Respiratory Syncytial Virus Replication by Nucleoside Analogues and Bis(indole) Compounds Dr. Donna Douglas - Mouse Models: Towards a Vaccine against HCV Infection Dr. Richard Wozniak - Rapid Production of Versatile Nanobody Repertoires Dr. Deborah Burshtyn - Impact of Sequence Variation on the Receptor for Human Cytomegalovirus Immune Evasion Protein UL18

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2018 AT A GLANCE

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


2018 FUNDING EXTERNAL FUNDING SOURCES (2018 = $22,541,867 CAD)

$19,109,040

$3,432,827

NOTE : Only the amount corresponding to 2018 is included.

MAJOR EXTERNAL FUNDING AWARDED (Only LKSIoV member listed, along with their role and total value awarded) NAME Troy Baldwin

Amit Bhavsar

ROLE

PROJECT TITLE

FUNDING AGENCY

AMOUNT1

PERIOD

PI

Regulation of T cell central tolerance by non-apoptotic mechanisms

CIHR

$868,275.00

2018 - 2023

Co-I2

Genomic and outcomes database for pharmacogenomics and implementation studies (Go-PGx)

$4,650,000.002

2018 – 2022

$80,000.00

2018 – 2022

CIHR

$25,000.002

2018 – 2019

CIHR

$703,000.002

2018 – 2022

CIHR

$841,500.00

2018 – 2023

CIHR

$765,000.00

2018 – 2023

NHMRC (Australia)

$18,760,000.002

2018 – 2022

CIHR

$879,750.00

2018 – 2023

PI Carla Coffin Shokrollah Elahi David Evans

Co-I2 Co-I2 PI

Canada Research Chair (Tier 2) in Functional Genomic Medicine CanHepC Basic Science Pilot Research Grant Biochemical characterization of Host DDX3X-HCV RNA Interaction Required for Viral Replication Pilot study of emtricitabine, tenofovir alafenamide and raltegravir for patients with primary biliary cholangitis Poxvirus replication and recombination as drivers of evolution Characterization of the relationship between innate immune activation and intestinal stem cell homeostasis NHMRC Program Grant RNA-dependent RNA polymerases of negative-sense RNA viruses

Genome Canada/CIHR, Large Scale Applied Research Project Canada Research Chairs

Edan Foley

PI

Michael Good

Co-I2

Matthias Götte

PI

Michael Hawkes

PI

Neuroprotective agents for cerebral malaria

CIHR

$251,561.00

2018 – 2021

Tom Hobman

Co-I2

Canadian HIV-ageing multidisciplinary programmatic strategy (CHAMPS) in NeuroHIV

CIHR

$2,500,000.002

2018 – 2023

Katharine Magor

PI

Influenza detection and innate defenses in the reservoir host

CIHR

$715,276.00

2018 – 2023

Andrew Mason

PI

CIHR

$780,000.00

2018 – 2022

Xiaoli Lilly Pang

Co-I2

Pilot study of Tenofovir Alafenamide, Emtricitabine and Raltegravir therapy for patients with primary biliary cholangitis Evaluating microbial risks and performance criteria for safe management of stormwater and rainwater use in Alberta

NSERC

$430,000.002

2018 – 2021

Trushar Patel

PI

Interaction studies of purified biomolecules

CFI & Alberta Economic Development and Trade Research Capacity Program

$343,458.00

2018 - 2023

Maya Shmulevitz

PI

CIHR

$787,950.00

2018 - 2023

Jack Tuszynski

PI

NSERC

$205,000.00

2018 – 2023

Richard Wozniak

PI

CIHR

$772,650.00

2018 – 2023

Understanding and exploiting post-entry steps of oncolytic reovirus replication and assembly Biophysical properties of tubulin and microtubules and their nano-biotechnology potential Function of Flaviviridae viral RNAs in the host cell nucleus

NOTE Amount listed is the total amount awarded for the entire period listed. NOTE 2: As a co-investigator, the amount of the award listed is divided amongst other co-investigators on the same project (not listed). 1:

2018 Li Ka Shing Institute of Virology Annual Report

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LKSIOV TEAM LEADERSHIP

D. Lorne Tyrrell, OC, AOE, MD, PhD, FRCPC, FRSC, FCAHS Founding Director, Li Ka Shing Institute of Virology Co-Director, Li Ka Shing Applied Virology Institute OPERATIONS

Carla Craveiro Salvado, PhD Operations and Research Manager

Bonnie Bock Administrative Assistant, Office of Dr. Tyrrell

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


GOVERNANCE

LKSIoV OVERSIGHT COMMITTEE Dr. Dennis Kunimoto (Committee Chair; Interim Dean, Faculty of Medicine and Dentistry) Dr. Walter Dixon (Associate Vice-President, Research) Dr. Michael Houghton (Director, Li Ka Shing Applied Virology Institute) Dr. Matthias Götte (Chair, Department of Medical Microbiology & Immunology) Dr. Sandra Davidge (Executive Director, Women & Children's Health Research Institute) Ms. Laura Kilcrease (CEO, Alberta Innovates) Mr. Doug Goss (Lawyer, Bryan & Company LLP) Dr. D. Lorne Tyrrell (Director, LKSIoV) (ex-officio) Dr. Carla Craveiro Salvado (Operations and Research Manager, LKSIoV) (ex-officio) LKSIoV MANAGEMENT & REVIEW ADVISORY COMMITTEE Dr. Troy Baldwin (Committee Chair, Dept of Medical Microbiology & Immunology) Dr. Matthias Götte (Chair, Dept of Medical Microbiology & Immunology) Dr. Maya Shmulevitz (Associate Professor, Dept of Medical Microbiology & Immunology) Dr. Katharine Magor (Professor, Dept of Biological Sciences) Dr. Rineke Steenbergen (Research Associate, Dept of Medical Microbiology & Immunology) Mr. Cameron Griffiths (PhD Candidate, Dept of Medical Microbiology & Immunology) Dr. D. Lorne Tyrrell (Director, LKSIoV) Dr. Carla Craveiro Salvado (Operations and Research Manager, LKSIoV) LKSIoV SCIENTIFIC ADJUDICATION COMMITTEE – RESEARCH SUPPORT & INNOVATION GRANTS Dr. D. Lorne Tyrrell (Committee Chair; Director, LKSIoV) Dr. Katharine Magor (Professor, Dept of Biological Sciences) Dr. William Albritton (University of Saskatchewan) Dr. Hans van de Sande (University of Calgary) Dr. Carla Craveiro Salvado (Committee Scientific Officer; Operations and Research Manager, LKSIoV) LKSIoV ADJUDICATION COMMITTEE – TRAINEE AWARDS Dr. Carla Craveiro Salvado (Committee Chair; Operations and Research Manager, LKSIoV) Dr. Maya Shmulevitz (Associate Professor, Dept of Medical Microbiology & Immunology) Dr. Katharine Magor (Professor, Dept of Biological Sciences) Trainee Representatives

2018 Li Ka Shing Institute of Virology Annual Report

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MEMBERSHIP The Li Ka Shing Institute of Virology is committed to supporting excellence in research. Our membership consists of investigators dedicated to making an impact on human health by focusing on viral pathogenesis, vaccine development, correlates of immunity, enhancement of vaccine efficacy, oncolysis, development of novel antivirals, amongst other areas. Our Full Members are Faculty appointees, including Faculty Service Officers, and/or clinical academic colleagues, eligible to apply for and hold research funding at the University of Alberta. Our Associate Members are research and/or clinical academic colleagues with a primary appointment at an institution that is not the University of Alberta; they must also be eligible to apply for and hold research funding at a recognized University.

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


Full Members

2018 Li Ka Shing Institute of Virology Annual Report

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MEMBERSHIP

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


2018 Li Ka Shing Institute of Virology Annual Report

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MEMBERSHIP

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


Associate Members

2018 Li Ka Shing Institute of Virology Annual Report

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OUR IMPACT IN 2018

LKSIoV RESEARCH SUPPORT AND INNOVATION GRANTS – December 1, 2018 Competition Dr. Shokrollah Elahi (Development of a Novel Live Microbicide to Prevent and Eliminate HIV Infection) Dr. Xiaoli Lilly Pang (Optimization of a New Model for Replicating Human Norovirus in Human Intestinal Enteroids) Dr. Stephanie Yanow (Advanced Epitope Mining for a Vaccine to Prevent Placental Malaria Infections) LKSIoV DOCTORAL STUDENT AWARD RECIPIENTS - October 1, 2018 Competition Ms. Nafiseh Ghobakhloo (Ostergaard Lab) Mr. Quinn Storozynsky (Hitt Lab) Ms. Julia May (Baldwin Lab) LKSIoV GRADUATE STUDIES ENTRANCE AWARD RECIPIENTS – October 1, 2018 Competition Mr. Cole Delyea (Bhavsar Lab) Ms. Melika Motamedi (Elahi Lab) Mr. Kevin Joannou (Baldwin Lab) Ms. Madeleine Wiebe (Yanow Lab) JOHN THIBAULT STUDENT TRAVEL AWARD RECIPIENTS – August 13, 2018 Competition Ms. Ghazal Babolmorad (Bhavsar Lab) Mr. Garett Dunsmore (Elahi Lab) LKSIoV TRAINEE TRAVEL AWARD RECIPIENTS – September 1, 2018 Competition Ms. Lee Campbell (Magor Lab) Ms. Janelle Johnson (Houghton lab) Ms. Farah Elawar (Marchant Lab) Dr. Michael Joyce (Tyrrell Lab) Mr. Danyel Evseev (Magor Lab) Ms. Angie Mena Palacios (Yanow Lab) Mr. Cameron Griffiths (Marchant Lab) Dr. Deanna Santer (Houghton Lab) LKSIoV TRAINEE TRAVEL AWARD RECIPIENTS – December 1, 2018 Competition Mr. Garett Dunsmore (Elahi Lab) Ms. Melika Motamedi (Elahi Lab) Dr. Maria Hasing (Pang Lab) Dr. Isobel Okoye (Elahi lab) Ms. Julia May (Baldwin Lab) LKSIoV-SPONSORED VISITING SPEAKERS (IMMUNET SEMINAR SERIES PARTNERSHIP) March 22, 2018 - Dr. Rodney Dekoter, Western University (Canada) May 24, 2018 - Dr. Alexandre Corthay, Oslo University (Norway) September 27, 2018 - Dr. Stephanie Karst, University of Florida (USA) Li Ka Shing Institute of Virology • www.uab.ca/lksiov


STATEMENT OF OPERATIONS STATEMENT OF OPERATIONS FOR THE CALENDAR YEAR ENDED DECEMBER 31, 2018 REVENUE AMOUNT ($ CAD) LKSIoV Endowment Spending Allocation 500,000 External Donor 7,000 (LKSIoV Trainee Travel Award Match-Up Donation) LKSIoV/GSK Endowment Spending Allocation 220,000 TOTAL REVENUE 727,000 EXPENDITURES AMOUNT ($ CAD) LKSIoV Graduate Studies Entrance Awards 40,000 LKSIoV Doctoral Student Awards 37,500 John Thibault Student Travel Awards 1,200 LKSIoV Trainee Travel Awards 12,484 ImmuNet/LKSIoV Visiting Speaker Sponsorships 1253 Research Support & Innovation Grants 179,300 RAT TRAP Seminars - Sponsorship 403 ImmuNet Research Day (IRD 2018) – Sponsorship 2,500 Website Development 6,000 10X Genomics Chromium System 220,000 TOTAL EXPENDITURES 500,640 REVENUE DISTRIBUTION

EXPENDITURES DISTRIBUTION

(Expenditure percentages do not include administrative expenses)

2018 Li Ka Shing Institute of Virology Annual Report

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ACCOLADES The LKSIoV is extremely proud of all its members. In 2018, many members received respected awards for their exceptional work, demonstrating their commitment to research excellence. Congratulations to all recipients!

MEMBER AWARDEES in 2018 Dr. Carla Coffin - Alberta Society of Gastroenterology Researcher of Year Award Dr. Shokrollah Elahi - Early Career Travel Award, American Association of Immunologists Dr. Michael Good - Fellowship of the National Heart Foundation of Australia; Appointed to the Program Committee of the American Society of Tropical Medicine and Hygiene Dr. Michael Hawkes - Stollery Hospital Distinguished Researcher Award Dr. Tom Hobman – University of Alberta Faculty of Medicine & Dentistry Canada 150 Research Award Dr. Michael Houghton - American Liver Foundation - Distinguished Scientific Achievement Award Dr. Norman Kneteman - Alberta Medical Association Distinguished Services Award Dr. Katharine Magor - BGSA FoS Graduate Student Mentoring Award Nominee Dr. Andrew Mason - Canadian Association for the Study of Liver & Canadian Liver Foundation, Visiting Professorship Dr. Xiaoli Lilly Pang - President's Excellence Awards - Outstanding Achievement in Innovation & Research, Alberta Health Services Dr. D. Lorne Tyrrell - Friends of the CIHR Award of Honour Li Ka Shing Institute of Virology • www.uab.ca/lksiov


TRAINEE MEMBER AWARDEES in 2018 BHAVSAR LAB Ghazal Babolmorad:

BALDWIN LAB Kevin Joannou: 1)

LKSIoV Recruitment Award

1) 2) 3) 4) 5)

Queen Elizabeth II Studentship FGSR Doctoral Recruitment Award FoMD Dean’s Doctoral Award LKSIoV Doctoral Award LKSIoV Travel Award

1)

Julia May:

2) 3)

FoMD Graduate Student Recruitment Scholarship WCHRI Graduate Studentship John Thibault Travel Award

1) 2)

LKSIoV Graduate Studies Entrance Award FoMD 75th Anniversary Award

Cole Delyea:

ELAHI LAB Najmeh Bozorgmehr: 1)

Medical Science Graduate Program Scholarships

Garett Dunsmore: 1)

John Thibault Travel Award Queen Elizabeth II Graduate Scholarship LKSIoV Graduate Studies Entrance Award FoMD 75th Anniversary Award FoMD/AHS Graduate Student Recruitment Scholarship

Afshin Namdar: 1)

Canadian Society for Immunology Travel Award

Isobel Okoye:

LKSIoV Travel Award

1)

LKSIoV Travel Award

Janet Sperling:

1) The People’s Choice Award, 3-Minute Thesis

MARCHANT LAB Farah Elawar: 1)

BioCanRX Travel Award

1) 2)

Queen Elizabeth II Graduate Scholarship FoMD 75th Anniversary Award

Shima Shahbaz:

1) 2) 3)

T. Wegmann Award FoMD 75th Anniversary Award Top impact factor paper, Dept of MMI

BARAKAT LAB Francesco Gentile: 1) 2) 3)

Alberta Innovates Graduate Student Scholarship Canadian Cancer Society Travel Award SciNet HPC Summer School Scholarship (Declined)

Subha Kalyaanamoorthy: 1)

NSERC Postdoctoral Fellowship

HEMMINGS LAB Yuliya Fakhr: 1)

Medical Sciences Graduate Program Scholarship

LKSIoV Travel Award

Cameron Griffiths: 1) 2)

1)

LKSIoV Travel Award Young Investigator Award, RSV2018

Ran Zhuo: 1)

HOUGHTON LAB Janelle Johnson:

TYRRELL LAB 1) 2)

Frederick Banting and Charles Best Canada Graduate Scholarship - Master’s

Alberta Innovates MD/PhD Studentship Alberta Cancer Prevention Legacy Fund MD/PhD Studentship Research Allowance

YANOW LAB

PANG LAB

ASM Clinical Virology Symposium Travel Award

Connie Le:

HITT LAB Quinn Storozynsky: 1)

1)

Danyel Evseev:

Melika Motamedi: 1) 2) 3) 4)

MAGOR LAB Lee Campbell:

BURSHTYN LAB Kang Yu:

1) 2)

HCV 2018 Bursary Award LKSIoV Travel Award

1)

LKSIoV Travel Award

Deanna Santer:

GOOD LAB

Angie Mena:

Shahareheh Eskandari:

1)

LKSIoV Travel Award

1)

Scholarship, Sao Paolo Vaccinology Course

1) 2)

Alberta Innovates Graduate Studentship Young Investigator’s Award, American Society of Tropical Medicine & Hygiene Annual Mtg WCHRI Graduate Studentship Queen Elizabeth II Diamond Jubilee Top Oral Presentation, IRD 2018

1)

Scholarship, Sao Paolo Vaccinology Course

1)

Best Mid-career Researcher Award, Institute for Glycomics, Griffith University

Catherine Mitran:

3) 4) 5)

Manisha Pandey:

Madeleine Wiebe: 1)

Edmonton Community Foundation Tuition Scholarship

2) 3)

Travel Award, 2018 International Hepatitis B Virus Meeting, Italy Travel Award, Canadian Society for Virology Postdoctoral Fellowship, Canadian Network on Hepatitis C

Tyler Mrozowich: 1)

COFFIN LAB Keith Lau: 1) 2) 3)

CIHR Graduate Student Award / Cumming School of Medicine University of Calgary Izaak Walton Killam Doctoral Scholarship 2018 HBV Conference Travel Award

1) 2) 3)

Queen Elizabeth II Scholarship – MSc 2018 International HBV Meeting - Best Poster, Italy 2018 HBV Conference Travel Award

1) 2)

CanHepC Trainee Stipend 2018 HBV Conference Travel Award

1) 2)

2018 Research Topics in GI Disease XVII Meeting Travel Award University of Calgary Student’s Union Travel & Conference Funding Ideas Award

Aaron Lucko:

PATEL LAB Vanessa Meier-Stephenson: 1)

Danielle Stanisic:

Travel Award, Canadian Society for Virology

Vanessa Meier-Stephenson: Nishi Patel:

2018 Li Ka Shing Institute of Virology Annual Report

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Li Ka Shing Institute of Virology • www.uab.ca/lksiov


LI KA SHING APPLIED VIROLOGY INSTITUTE The Li Ka Shing Applied Virology Institute (AVI) was established as the translation and commercialization hub of the Li Ka Shing Institute of Virology. The AVI’s mission is to help transition nascent technologies in the life sciences sector into clinical relevance, providing funding, technology development support, and commercialization guidance.

Since its inception in 2013, the AVI has achieved many of its goals, including:  The set up and operation of a state-of-the-art computational centre;  The recruitment of high-calibre professionals to form a stimulating biotech environment;  The filing of multiple patent applications;  The incorporation of multiple start-ups for the future commercialization of the nascent technologies.

DR. MICHAEL HOUGHTON Message from the AVI Director

Dr. Michael Houghton 2018 Li Ka Shing Institute of Virology Annual Report

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GOVERNANCE

LKSAVI SCIENTIFIC ADVISORY BOARD Dr. Devron Averett (Partner at AgriTitan LLC) Dr. Stephen Burley (Rutgers School of Arts and Sciences) Dr. Walter Dixon (Associate Vice-President, Research, University of Alberta) Dr. Michael Gale Jr. (University of Washington) Mr. Tim Murphy (Alberta Innovates) Dr. John McHutchison (Head of Research and Development, Gilead) Dr. Amy Weiner (Bill & Melinda Gates Foundation)

LKSAVI SCIENTIFIC ADVISORY COMMITTEE – IMMUNE CHECKPOINT PROGRAM Dr. Daniel Lamarre (Université de Montréal) Dr. Rima Al-awar (University of Toronto) Dr. Naglaa Shoukry (Université de Montréal) Dr. John Bell (Ottawa Hospital Research Institute and University of Ottawa)

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


AVI AT A GLANCE IN 2018

PATENTS FILED &/or ISSUED in 2018 1. 2. 3. 4. 5. 6.

Tyrrell DL, Steenbergen HG, Joyce M. “Methods for Producing Cells Having a Phenotype of a Primary Human Hepatocytes and Compositions” USPTO 14/423,991 filed 2/25/2015. Issued May 15, 2018. Landi A, Houghton M, Tyrrell DL, Lankisch T, Weismueller T, Manns M. “Methods and Compositions for Diagnosis of Inflammatory Liver Disease” Japanese Patent Application 2015-530512 filed Sep 6, 2013. Issued Sep .14, 2018 Landi A, Houghton M, Tyrrell DL, Lankisch T, Weismueller T, Manns M. “Methods and Compositions for Diagnosis of Inflammatory Liver Disease” Divisional Patent Application 15/357,841 filed Nov 21, 2016. Issued Apr 24, 2018 Gotte M, Tchesnokov EP. “Recombinant RNA-Dependent RNA Polymerase of RNA Viruses” PCT Patent Application filed Sep 4, 2018. Landi A, Houghton M, Tyrrell DL, Bonino F, Maurizia Rossan B, Clementin A. “Biomarkers in AutoImmune Liver Disease” PCT Patent Application PCT/US2018/055280 filed Oct 10, 2018. Hobman TC, Power C, Xu Z. “Use of Peroxisome Biomarkers for Predicting HIV Disease Progression and for Treatment Peroxisome Activating Drugs” PCT Patent Application PCT/CA2018/050541. Filed May 7, 2018.

AVI-SUPPORTED PATENTS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Egli A, Santer D, Houghton M, Tyrrell DL et al. “Immunomodulatory Peptides and Methods of Use Thereof” USPTO 14/443,630 filed May 18, 2018. Landi A, Houghton M, Tyrrell DL, Lankisch T, Weismueller T, Manns M. “Methods and Compositions for Diagnosis of Inflammatory Liver Disease” USPTO 14/423,998 filed Feb 25, 2015. Issued January 3, 2017. Houghton M, Hockman D, Law J, Logan M, Tyrrell DL. “E1E2 HCV Vaccines and Methods of Use” PCT Patent Application IB2015/001573 filed May 20, 2015. Evans D, Gammon DB. “Oncolytic Viruses and Methods for Treating Neoplastic Disorders” USPTO 13/383,396. Filed July 10, 2009; issued Mar 25, 2014. Landi A, Houghton M et al. “Methods and Compositions in Diagnosis of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis” PCT Patent Application CA2016/000022 filed Jan 26, 2016. Houghton M, Logan M et al. “Hepatitis C Virus Immunogenic Compositions and Methods of Use Thereof” PCT Patent Application IB2016/001051 filed July 6, 2016. Houghton M, Logan M et al. “Hepatitis C Virus E1/E2 Heterodimers and Methods for Producing Same” PCT Patent Application IB2016/056000 filed October 7, 2016. Noskov S, Wacker S, Duff H, Guo J, Houghton M. “Systems and Methods of Selecting Compounds with Reduced Risk of Cardiotoxicity of Molecular Parameters of a Compound based on Machine Learning Algorithms” PCT Patent Application PCT/CA2016/050705 filed June 16, 2016. Houghton M, Tyrrell L, Barakat K, Nieman J, Ahmed M. “Small Molecule Immunomodulators” USPTO 62/466,243 filed March 2, 2017 Bhat R, Houghton M. “Recombinant Cardiomyocytes and Cardiomyocyte Cell Lines Expressing hERG”. PCT Patent Application PCT/CA2017/051076 filed September 13, 2017. Jhamandas J, Soudy R, Kaur K, Fu W, MacTavish D, Patel A. “Brain Penetrant Amylin Receptor Based Peptides for Alzheimer's” USPTO 62/396,370 filed Sep 16, 2016. Houghton M, Landi A, Logan M, Law J, Hockman D, Chen C. “Hepatitis C Virus Immunogenic Compositions and Methods of Use Thereof” USPTO 62/397,763 Application filed September 21, 2016. Houghton M, Landi A, Hockman D, Law J, Logan M. “Hepatitis C Virus Immunogenic Compositions and Methods of Use Thereof” PCT Patent Application PCT/CA2017/051192 filed October 5, 2017. Landi A, Houghton M, Tyrrell DL, Bonino F, Maurizia Rossan B, Montano-Loza A, Clementin A. “Biomarkers in AutoImmune Liver Disease” PCT Patent Application PCT/US2018/055280; filed October 18, 2018. Magor K, Xiao Y. “RIG-I Promotor and Compositions and Methods Relating to Same” USPTO 62/564,867 filed Sep 28, 2017.

2018 Li Ka Shing Institute of Virology Annual Report

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AVI-INCUBATED PROJECTS SNAPSHOT OF THE MAJOR PROJECTS INCUBATED BY THE AVI IN 2018 PROJECT

PROJECT LEADER

An Oncolytic Virus to Treat Cancer

Dr. David Evans

Tubulin 3targeted Cancer Chemotherapy

Dr. Jack Tuszynski

FEATURES

STATUS

NEXT STEPS

PARTNERING

Patents issued. Animal efficacy demonstrated. Master Virus Bank made. Patents filed. Animal efficacy against human bladder cancer cells shown. Patents filed. Animal efficacy against mucosal and skin transmission. Unique approach. Use of artificial intelligence for drug design.

MVB being tested for clinical release

Pre-clinical toxicity testing

Genesail (Shanghai) in progress

Clinical lots being prepared

Manufacturing and pre-clinical toxicity testing

Future funding provided by private Alberta investor

Clinical lots being prepared

Manufacturing and pre-clinical toxicity testing

Griffiths University (Brisbane, Australia) to fund human challenge efficacy trials

Active small molecule drugs identified

Hit-to-Lead in progress

U of A Hospital Foundation

Confirming correlation in more patients

In discussions with MSD(USA) & Gilead

Group A Strep Vaccine

Dr. Michael Good

Alzheimer’s Therapy

Dr. Jack Jhamandas

Autoimmune Liver Disease Diagnostics

Dr. Amir Landi & Dr. Ana Clementin

Patents issued.

Correlates with liver inflammation

CMV Antiviral

Dr. James Nieman

Salvaging of a Pharma drug.

More active and less toxic drug identified

Small Molecule Immune Checkpoint Inhibitors

Dr. Khaled Barakat

Designed using artificial intelligence. (patent filed)

Active hits targeting CTLA4 identified

HCV Vaccine

Dr. Michael Houghton & Dr. D. Lorne Tyrrell

One of two clinical candidates worldwide.

Manufacturing for clinical testing in progress

Animal pharmacokinetics & hematopoietic cell toxicity tests Increasing activity and demonstrating acceptable ADME Complete GMP manufacturing followed by pre-clinical toxicity testing

Li Ka Shing Institute of Virology • www.uab.ca/lksiov

Merck interested to discuss more details

Gilead (USA) offer to test in their labs Partnered with Helmholz Institute, Germany (1.3 million Euros). In collaborative talks with the US NIH.


AVI-INCUBATED PROJECTS (CONT’D) ADDITIONAL AVI-INCUBATED CO-FUNDED PROJECTS

PROJECT Hepatocyte Cell Line

PROJECT LEADER Dr. Rineke Steenbergen, Dr. Michael Joyce & Dr. D. Lorne Tyrrell

A small molecule for the treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)

Dr. Kamlesh Sahu & Dr. Michael Houghton

A Drug against HIV-Associated Dementia

Dr. Tom Hobman & Dr. Chris Power

Group B Streptococcus Vaccine Antigen

Dr. Greg Tyrrell

A Transgenic Method to Render Chickens Resistant to Fowl Plague

Dr. Katharine Magor

A Test for Panviral Polymerase Inhibitors

Dr. Matthias Götte

Cell lines and in silico tools for toxicity prediction A Diagnostic Test for Chronic Fatigue Syndrome (CFS)

Dr. Sergei Noskov (University of Calgary) & Dr. Michael Houghton Dr. Amir Landi, Dr. Michael Houghton & Dr. D. Lorne Tyrrell

A Drug for Herpesvirus (RAFIs)

Dr. Luis Schang

RSV Reagent commercialization

Dr. Maya Shmulevitz

IL-28B

Dr. Deanna Santer & Dr. Michael Houghton

A small molecule inhibitor in the TNF-alpha pathway

Dr. Edan Foley

RSV antivirals

Dr. David Marchant & Dr. Fred West

2018 Li Ka Shing Institute of Virology Annual Report

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AVI TEAM LEADERSHIP

OPERATIONS

CHEMISTRY

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


AVI TEAM (CONT’D) CHEMISTRY (continued)

GMP MAMMALIAN CELL MANUFACTURING

2018 Li Ka Shing Institute of Virology Annual Report

Page 24


AVI TEAM (CONT’D) GMP PROTEIN PURIFICATION

VIROLOGY

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


AVI TEAM (CONT’D) IMMUNOLOGY

PROTEIN ANALYTICS

DRUG DESIGN / ARTIFICIAL INTELLIGENCE

QUALITY CONTROL AND QUALITY ASSURANCE

2018 Li Ka Shing Institute of Virology Annual Report

Page 26


AVI TEAM (CONT’D) IN 2018, THE AVI WELCOMED TWO HIGHLY QUALIFIED SCIENTISTS TO THE TEAM JANELLE JOHNSON, BSc, MSc Laboratory Technician With several years of experience as a laboratory and animal technician and a recent MSC graduate from the Department of MMI, Janelle is involved with several aspects related to the development, testing, and production of the HCV vaccine. Janelle has multiple roles in the AVI. She collaborates with the coordination of the AVI laboratory, and most importantly, she is a member of the downstream GMP protein purification team, contributing to the purification of a protease required for the manufacturing process, as well as assisting the team with the purification of the HCV vaccine.

LOUISE TAN, BSc Quality Assurance / Regulatory Affairs Specialist With over 25 years of experience in working for biopharmaceutical companies that had products enter phase III clinical trials, Louise has extensive working knowledge in setting up and implementing Quality Management System (QMS), Quality Control and validation programs that comply with Good Manufacturing Practices (GMP) from various jurisdictions (FDA, Health Canada, EU, ICH, WHO) for mammalian, bacterial and insect cell lines as well as implementing ISO 15189 Standards for Medical Laboratory.

    

At the AVI, Louise manages the Quality Assurance, Quality Control and Regulatory Affairs department where she assures quality is built into the Hepatitis C vaccine product. She sets up quality policies and QMS including, but not limited to: All chemicals, reagents, consumables, etc. are sourced from the highest possible grade and equipment are qualified for GMP purposes; Quality Control test results are reliable, accurate and reproducible; Every lot of drug substance and drug products destined for clinical trials are manufactured under GMP conditions and meet the specifications required by appropriate regulatory agencies; Appropriate training programs are set up and well documented; GMP documentation control, Change Control, Deviation and OOS investigation systems are in place and followed.

Louise is also responsible for conducting internal and external audits to ensure GMP compliance, data and documentation review and analysis, as well as gathering, collating and preparing documentation for Investigational New Drug (IND) submissions and liaises with regulatory authorities before, during, and after each clinical trial for reporting of clinical results.

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


AVI FUNDING SOURCES THE AVI GRATEFULLY ACKNOWLEDGES THE SUPPORT OF ITS MAJOR FUNDERS

SUMMARY OF 2018 FUNDING SOURCES 2010 - 2018

Viral Hepatitis & Inflammatory Disease Principal Investigator: Michael Houghton Canadian Institutes of Health Research (CIHR) Canada Excellence Research Chair (CERC) in Virology Total Funded Amount: $10,000,000

2013 - 2018

Development of a vaccine against the hepatitis C virus (HCV) and demonstration of efficacy in intravenous drug users Co-PIs: Michael Houghton & D. Lorne Tyrrell Alberta Innovates - Health Solutions (AIHS) Collaborative Research & Innovation Opportunities (CRIO) Total Funded Amount: $5,000,000

2013 - 2019

Alberta Innovates Health Solutions Grant to the Li Ka Shing Applied Virology Institute Co-PIs: D. Lorne Tyrrell & Michael Houghton Total Funded Amount: $30,000,000

2015 - 2020

Immune checkpoints PI: Khaled Barakat; Co-PI: Michael Houghton Alberta Cancer Foundation Grant Total Funded Amount: $2,400,000

2018 Li Ka Shing Institute of Virology Annual Report

Page 28


PARTNERSHIPS & COLLABORATIONS The Li Ka Shing Institute of Virology (LKSIoV) unites a consortium of over 40 exemplary researchers. Although most LKSIoV members are associated with the Department of Medical Microbiology and Immunology at the University of Alberta, member affiliation encompasses a combined 28 Institutes, Departments and Faculties at the University of Alberta. Additionally, some of our members are located in other institutions. The success of our members, and ultimately the LKSIoV, is dependent on both intra- and inter-collegiate connections, including other local, national, and international collaborators. At a glance, LKSIoV members have collaborators in: 

28 Institutes or Departments or Faculties at the University of Alberta;

32 Institutions within Canada; and

73 Institutions in 21 countries around the world!

NOTE: Locations of partners or collaborators with Li Ka Shing Institute of Virology members are highlighted in green on the world map.

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


PARTNERSHIPS & COLLABORATIONS LOCAL & NATIONAL COLLABORATORS University of Alberta Campus Saint-Jean Department of Biology Faculty of Agricultural Life and Environmental Sciences Faculty of Medicine & Dentistry FoMD Core Facility, Cell Imaging Centre Department of Biochemistry Department of Cell Biology Department of Dentistry Department of Laboratory Medicine and Pathology Department of Medical Microbiology and Immunology Department of Medicine Division of Gastroenterology Division of Hematology Division of Infectious Diseases Division of Neurology Division of Pulmonary Medicine Department of Obstetrics and Gynecology Department of Oncology Department of Pediatrics Department of Surgery Faculty of Pharmacy and Pharmaceutical Sciences Faculty of Science Department of Biological Sciences Department of Chemistry Department of Mathematic Department of Physics Li Ka Shing Institute of Virology (LKSIoV) School of Public Health Women & Children’s Health Research Institute (WCHRI)

Edmonton Alberta Boyle McCauley Health Centre ContraVir Pharmaceuticals Institute of Health Economics Provincial Laboratory for Public Health (ProvLab) StreetWorks

Canada Canadian Food Inspection Agency (CFIA), Winnipeg MB Canadian Institutes of Health Research, Ottawa ON Canadian Nosocomial Infection Surveillance Program Canadian Public Health Laboratory Network Children’s Hospital of Eastern Ontario Research Institute, Ottawa ON Gilead Sciences Industry Partnered Collaborative Research GlaxoSmithKline Industry Partnered Collaborative Research INRS-Institut Armand Frappier, Laval QC Janssen Pharmaceuticals, Toronto ON McGill University, Montréal QC Montreal University Hospital Center Centre Hospitalier de l'Université de Montréal (CHUM) National Microbiology Lab Polytechnique Montréal, Montréal QC Public Health Agency of Canada Spring Bank Pharmaceuticals Transgene SA University of British Columbia, Vancouver BC University of Calgary, Calgary AB University of Guelph, Guelph ON University of Lethbridge, Lethbridge AB University of Manitoba, Winnipeg MB Université de Montréal, Montréal QC University of Ottawa, Ottawa ON University of Saskatchewan, Saskatoon SK Université de Sherbrooke, Sherbrooke QC University of Toronto, Toronto ON University of Western Ontario, London ON

INTERNATIONAL COLLABORATORS Australia Griffith University, Southport QLD James Cook University, Townsville QLD Monash University, Melbourne QIMR Berghofer Medical Research Institute, Herston QLD Sanaria Pty Ltd, Brisbane QLD The Walter and Eliza Hall Institute of Medical Research, Parkville VIC University of Melbourne, Melbourne University of Queensland, Brisbane QLD

China Cumming School of Medicine Global Health Office (China), (Partner Universities: Harbin University, Sun-Yat-sen University, Beijing Capital Medical University Beijing You’An Hospital, Capital Medical University, Beijing Beijing Genomics Institute (BGI), Shenzhen PLA Second Military Medical University, Shanghai

Columbia Universidad de Antioquia, Medellín

Brazil FIOCRUZ Instituto Oswaldo Cruz, Rio de Janeiro

Denmark Statens Serum Institut, Copenhagen University of Copenhagen, Copenhagen

2018 Li Ka Shing Institute of Virology Annual Report

Page 30


PARTNERSHIPS & COLLABORATIONS INTERNATIONAL COLLABORATORS (cont’d) Ethiopia

United Kingdom

University of Gondar, Gondar

Oxford University, Oxford University of Birmingham, UK University of Nottingham, Nottingham

France INSERM (Institut national de la santé et de la recherche médicale) Université Paris Diderot, Paris Université de Strasbourg, Strasbourg

Germany Helmholtz Centre for Infection Research, Braunschweig Max Planck Institute for Ornithology, Radolfzell University of Cologne, Cologne

Iran Ferdowsi University of Mashhad, Mashhad

Israel

Technion – Israel Institute of Technology, Haifa

Italy Politecnico di Torino , Torino Università di Bologna, Bologna Università di Pisa, Pisa

Japan University of Tsukuba, Tsukuba

Norway Oslo University Hospital, Oslo University of Oslo, Oslo

Poland International Institute of Molecular and Cell Biology, Warsaw Medical University of Gdansk, Gdansk University of Poznań, Poznań

Serbia

United States of America Association of Public Health Laboratories Baylor College of Medicine, Houston TX Center for Infectious Disease Research, Seattle WA Chimerix, Durham NC Cincinnati Children’s Hospital Medical Center, Cincinnati OH Cornell University, Ithaca NY Department of Veterans Affairs Medical Center, Research Service, White River Junction, VT Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon, NH Gilead Sciences, Inc., Foster City, CA Harvard University, Cambridge, MA Los Alamos National Laboratory, Los Alamos, NM Molecular Virology & Microbiology, Baylor College of Medicine National Center for Immunization and Respiratory Diseases (NCIRD), Atlanta GA National Institutes of Health Research (NIH), Bethesda MD New York University School of Medicine, New York NY Rockefeller University, New York NY Seattle Children’s Hospital, Seattle, WA St. Jude Children’s Research Hospital, Memphis Tufts University, Boston United States Department of Agriculture (USDA) Exotic & Emerging Avian Viral Diseases Research, Athens GA University of California Davis, Davis CA University of Central Florida, Orlando University of Chicago, Chicago, IL University of Massachusetts, Amherst MA University of Minnesota, Minneapolis MN University of Nebraska, Lincoln, NE University of South Florida, Tampa FL University of Washington, Seattle WA

Wales

University of Novi Sad, Novi Sad

Cardiff University, Cardiff

Sweden Karolinska Institutet, Solna Karolinska University Hospital, Solna

Switzerland Hôpitaux Universitaires de Genève, Genève Scuola universitaria professionale della Svizzera italiana (SUPSI), Manno Université de Lausanne, Lausanne

Uganda Makerere University, Kampala

Li Ka Shing Institute of Virology • www.uab.ca/lksiov


To find out more about the Li Ka Shing Institute of Virology or the Li Ka Shing Applied Virology Institute, please visit us online at www.uab.ca/lksiov or contact us:

Li Ka Shing Institute of Virology 6-010 Katz Group Centre for Pharmacy and Health Research University of Alberta Phone: 780.492.1084 Fax: 780.492.5304 Email: lksiov@ualberta.ca

Li Ka Shing Applied Virology Institute 7-126 Li Ka Shing Centre for Health Research Innovation University of Alberta Phone: 780.248.5816 Fax: 780.492.5304 Email: lksavi@ualberta.ca 2018 Li Ka Shing Institute of Virology Annual Report

Page 32



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