Understanding human genome regulation through robust and multi-scale reference chromatin state annotations across hundreds of human cell types

Although researchers have identified tens of thousands of disease-associated genetic variants, the mechanisms driving most of these variants remains unknown. Most variants are believed to affect regulatory elements. However, regulatory elements are incompletely annotated and understood. Large-scale projects have recently generated thousands of epigenomic data sets. These data sets measure the regulatory activity of the genome in human cells. However, computational methods are needed to understand the link between genetic variation and disease.

We previously developed a computational method, Segway, that annotates genomic regulatory elements on the basis of epigenomic data sets. Enabled by new epigenetic data sets, this project will annotate the genome in hundreds of human cell types, and use these annotations to understand disease-associated genetic variation.

Additionally, we will develop computational methods that improve our ability to identify genomic elements. This outputs of this project will come in three forms:

  1. General-purpose software for annotating the genome.
  2. Easy-to-use reference data sets.
  3. Insights into the link between genetic variation and chronic obstructive pulmonary disease (COPD).

Healing Indicators: Research in Indigenous health impact assessment and self-determination

This Health System Impact Fellowship is co-funded by CIHR, MSFHR, and First Nations Health Authority (health system partner), to help build BC’s health policy research capacity for the integration of policy research into decision-making.

Healing Indicators is a research project that aims to improve health assessment policy. It addresses the need to create tools that centre communities and Indigenous knowledge in the assessment of the health impacts of resource development. The project is grounded in community-based Indigenous methods, with the purpose of developing land-based wellness indicators. The work draws on self-determination, culture, kinship, community, and land to inform and define health and wellness in a First Nations context. As a research program, Healing Indicators is committed to engaging land-based healing and health justice and features a decolonial ‘two-eyed seeing’ approach, with one eye informed by Indigenous ways of knowing, and the other western science. Progressing land-based indicator research is important within the context of the First Nations Health Authority’s “Public Health and Wellness Agenda.” Land-based health indicator development requires emergent community-based methods and design that is inclusive of leadership from Indigenous peoples. The impact of this collaboration is the promotion of critical Indigenous health research, with opportunities to expand on policy gaps in relation to land-based wellness and Indigenous health assessment. Asset-based work, such as this, is relevant within the context of provincially acknowledged widespread racism within the health care system in British Columbia. This work is also significant to the provincial commitment to implement the Declaration of the Rights of Indigenous Peoples (DRIPA 2019). Healing Indicators is a collaborative research project designed to promote community-led health through land-based indicator development to inform self-determination and wellness in collaboration with the First Nations Health Authority.

Source: CIHR Funding Decisions Database

General and inexpensive saliva-based viral RNA testing by direct imaging

In the absence of a vaccine and/or effective treatment, rapid and robust testing is vital not only to reduce the transmission and spread of SARS-CoV-2, but also for paving the way to safely reopen borders and reinstating the world economy. Most Covid-19 tests are performed using nasopharyngeal swabs that are sent to a hospital or public health laboratory to be processed for RT-PCR analysis using expensive equipment by technically trained staff. The specificity of such amplification-based tests makes them superior to many other detection tests. However, the occurrence of false-negative results due to the low levels of viral RNA found in such samples, as exemplified by recent problems with Spartan Cube1, suggests that avoiding nucleic acid amplification entirely and switching to the direct detection of viral RNA could be highly advantageous for SARS-CoV-2 detection.

Funded by the CIHR Rapid Research Opportunity and MSFHR, Dr. Peter Unrau is leading a team of researchers to develop a new saliva-based viral testing strategy for use in the current Covid-19 pandemic. Dr. Unrau (professor in RNA biochemistry) and co-investigator Dr. Forde (professor in biological physics) will coordinate a research team at Simon Fraser University. They will work in collaboration with David Rueda, a professor in single-molecule imaging at Imperial College London.

This COVID-19 research will allow the development of a fast, inexpensive and sensitive viral RNA test that, in principle, could be used for point of care testing at home. The proposed SARS-CoV-2 RNA single-molecule imaging test will be highly specific, will rely on simple well-understood chemistry, and will include an inexpensive imaging device that connects to a cell phone. An additional benefit of this device is that test procedures can easily be adapted for the screening of other RNA pathogens in the future.

Funding Competition: CIHR Operating Grant: COVID-19 Rapid Research Funding Opportunity – Diagnostics

Funders: CIHR; MSFHR

AIRWISE – A risk communication strategy for the prevention and early detection of respiratory illness

Co-lead: 

  • Renelle Myers 
    BC Cancer

Team members: 

  • Aleisha Fernandes
    SFU
  • Prabjit Barn
    Legacy for Airway Health
  • Stephen Lamb
    UBC, BC Cancer
  • Mohsen Sadatsafi
    RESP, UBC
  • Christopher Carlsten 
    UBC
  • Rita McCracken 
    UBC, PHC
  • Kevin Keen
    UNBC
  • Anne-Marie Nicol
    SFU, BCCDC
  • Milan Khara
    UBC, VCH
  • Pat Camp 
    UBC, HLI, PHC

Respiratory illnesses, such as asthma, chronic obstructive pulmonary disease, and lung cancer account for the leading causes of preventable deaths in British Columbia. Scientists can now identify people who are at a high risk of developing these devastating illnesses early on when it is possible to prevent, cure or slow the progression of disease. Prevention and early detection programs, however, don’t reach all members of the population equally. In addition, environmental radon and air pollution increase the risk of developing respiratory illnesses for people living in some areas of the province. This study is motivated by the need to expand the reach of prevention and early detection programs through risk communication. Our experienced team of researchers, community stakeholders, trainees, and knowledge translation specialists will define the risk information that is needed for future research and for communicating in clinical and community-based settings. Together, we will convene an advisory committee to design the first version of the AIRWISE risk communication platform and establish community coalitions to evaluate and implement it.

“HIV Made Me Fabulous:” Utilizing film for knowledge dissemination and stigma reduction

Co-lead:

  • Valerie Nicholson 
    BC Centre for Excellence in HIV/AIDS

Team members: 

  • Allison Carter
    SFU
  • Lori Brotto
    Women’s Health Research Institute
  • Nicole Prestley
    Women’s Health Research Institute
  • Melissa Nelson
    Women’s Health Research Institute
  • Juno Roche
    Sophia Forum
  • Edmond Kilpatrick
    SFU
  • Florence Anam
    Africa for MSF
  • Marvelous Muchenje
    ViiV Healthcare
  • Azra Bhanji
    SFU

People who have an undetectable viral load cannot transmit HIV during condomless sex. However, women living with HIV continue to face HIV-related stigma. “HIV Made Me Fabulous” is a short film (https://youtu.be/QamnyGc0gtY) grounded in current HIV science that invites audiences to understand the physically and emotionally charged experience of living and loving with HIV from a woman’s perspective. This project aims to disseminate the film to advance public understandings of sexuality and HIV, to reduce HIV-related stigma and improve the health of women living with HIV. 

Our team will:

  1. Host four virtual film screenings and facilitated discussions, and assess impacts among priority target audiences (i.e. women with HIV, providers/policymakers, the general public).
  2. Use findings from the screenings to develop a film discussion guide to support others (e.g. HIV support groups, care providers, gender equity leaders) to screen the film and facilitate safe, informed, and evidence-based discussions.
  3. Widely disseminate the film and discussion guide via YouTube, social media, and community/academic forums. Mixed methods will be used to evaluate the reach and impact of this innovative, arts-based, technology-driven KT project.

Eng/aging and HIV: Knowledge exchange between administrative data study and older adults living with HIV in British Columbia

Co-lead:

  • Valerie Nicholson 
    BC Centre for Excellence in HIV/AIDS

Team members: 

  • Kathleen Inglis
    SFU
  • Wayne Campbell
    AIDS Vancouver
  • Antonio Marante
    BC Centre for Excellence in HIV/AIDS
  • Patience Magagula
    Afro-Canadian Positive Network of BC
  • Silvia Guillemi
    BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Dr. Peter Centre
  • Andreea Bratu
    BC Centre for Excellence in HIV/AIDS

Since the 1980s, HIV/AIDS community groups have engaged with science to ensure that research is done with them instead of simply about them yet it is rare for communities to engage with studies using administrative health data — that is, data electronically generated at every encounter with the health care system for administrative or billing purposes. This is a collaborative project amongst researchers and people living with HIV that explores how to embody the “nothing about us without us” principle in administrative data studies to ensure ongoing authentic engagement across all HIV research. Engaging with an administrative data study called COAST at the B.C. Centre for Excellence in HIV/AIDS, we will co-develop, pilot, and evaluate a process to research the experience of aging with HIV. In B.C., over half of people living with HIV who are on treatment are over 50 years of age. People with HIV are living longer lives. Through a regular series of meetings with our research council, we aim to develop a way to leverage administrative data (COAST) to better understand the complex reality of aging with HIV that is relevant to people living with HIV, which may help improve health services and health outcomes for people living with HIV.

Automated body composition analysis for precision medicine applications

There is growing evidence showing that the amount of muscle and fat one has in the body influences various aspects of cancer such as carcinogenesis (formation of cancer), response to chemotherapy drugs (to decide on the optimal dosage to the patient to destroy cancer cells while avoiding damage in other organs), death resulting from complications due to surgery, and overall survival outcomes. Conversely, cancer also causes loss of muscle mass. Accurate and easily available tools are thus needed to measure muscle and fat in an individual in the context of cancer treatment decisions. CT images are almost universally acquired in cancer diagnosis and treatment planning, and these directly show muscle and fat in the body. But in order to extract measurements, manual intervention (which is tedious) or automated tools are needed. We are developing a fully automated 3D method to measure the amount of muscle and fat from 3D CT images available in the cancer clinic. The availability of these measurements will enable correct chemotherapy treatment dosage to be determined for each individual based precisely on their body composition, resulting in better health outcomes.

Multispectral RNA Mango: Synthesis of new multicolour fluorogens for incorporation into pathogen detection and identification kits

With the increasing prevalence of viral pathogens as exemplified by COVID-19, reliable and inexpensive detection is of increasing importance. Rapid testing allows appropriate and immediate treatment, which can have a profound effect on the treatment outcome. Early on-site detection is also greatly beneficial for hospitals and clinics since it would allow patients to be rapidly screened before entering the system.

Viruses and bacteria contain unique RNA fingerprints that can be used to identify their exact species. Recently, we have developed RNA Mango technology that can specifically and rapidly detect extremely low levels of RNA and that outcompetes the previous standard for RNA-based pathogen detection (RT-PCR) in terms of speed, while maintaining sensitivity. A limitation of our current technology is that it is not yet as reliable as it needs to be, since it is lacking controls for reaction failure — an important aspect for pathogenic detection and identification. In this application, we will further develop our RNA-detection technology into a rapid, multichannel, colour-based test that will allow us to quickly and reliably detect and identify multiple pathogens and expand its commercial in vivo applications.

Fucosylation inhibitors for convenient production of fucose-deficient antibodies

Therapeutic antibodies have revolutionized the treatment of cancers. The efficacy of many of these antibodies depends on their ability to recognize and bind to cancer cells. These antibodies then recruit immune cells to kill the cancer cells. Recent interest has focused on the different sugar molecules attached to the antibody and their role in helping or hindering the recruitment of immune cells. Specifically, eliminating one specialized sugar known as fucose from antibodies dramatically improves their ability to recruit immune cells and kill cancers. Industry is therefore interested in ways to prevent this sugar modification and to thereby produce improved anti-cancer antibodies.

We have developed a new family of chemical compounds that block the addition of fucose onto antibodies as they are being produced. We now aim to translate this work to drive the generation of improved therapeutic antibodies. Because the fucose-deficient antibodies are much more potent, it is expected that lower doses of these antibodies can be used leading to a lowered risk of side effects. Additionally, the increased potency should lead to improved efficacy of therapeutic antibodies and outcomes for cancer patients in British Columbia and elsewhere.

Evaluation of innovative risk mitigation services in the context of dual crises of COVID-19 and overdose among people who use opioids in Vancouver, BC

Through funding from the Canadian Institute of Health Research (CIHR) and MSFHR, Principal Investigators Dr. Kanna Hayashi, Research Scientist at the BC Centre on Substance Use (BCCSU) and St. Paul’s Hospital Chair in Substance Use Research and Assistant professor in the Faculty of Health Science at Simon Fraser University (SFU) along with Dr. Kora DeBeck, Research Scientist at the BCCSU and Associate Professor in the SFU School of Public Policy aim to conduct preliminary evaluation of two novel measures introduced by the BC government in March 2020 to address the dual crisis of overdose and COVID-19.

Specifically, these measures include expanding the opioid agonist treatment (OAT) prescription guidelines and pandemic prescribing of pharmaceuticals (e.g. opioids) to people who use illicit drugs. By providing pharmaceutical alternatives to the toxic illicit drug supply, the interventions are intended to reduce physical encounters involved in obtaining illicit drugs and the use of toxic street drugs, thereby supporting both overdose and COVID-19 prevention efforts. To date, however, the impacts of these interventions have not been evaluated.

The proposed BC-based research aims to fill critical knowledge gaps by examining the reach and preliminary impacts of pandemic prescribing and expanded OAT prescription services among people who use opioids in urban Vancouver. Through this work, the research team, which consists of highly productive investigators and knowledge users with direct clinical and policy expertise, seeks to inform efforts to improve the delivery and effectiveness of the interventions.

Funding Competition: CIHR Operating Grant: COVID-19 Mental Health & Substance Use Service Needs and Delivery Funding Opportunity

Funders: CIHR; MSFHR