On April 17-23, the HLI hosted its bi-annual High School Science Week (HSSW), the second session since the program was paused during the pandemic. Eight students from grades 11 & 12 from the Vancouver and Burnaby school districts were invited to tour the Centre’s lab facilities and get hands-on experience in molecular biology techniques.

Over the course of the week, students learned to do mammalian cell culture, identify blood cell types with flow cytometry and quantify proteins via western blotting, ELISA, and confocal microscopy. They participated in labs to learn about the basics of pulmonary function testing, cardiopulmonary exercise physiology, and immunology. Students were introduced to translational research and had an introduction to human tissue biobanking.

Dr. Gurpreet Singhera, a Research Associate and Manager of the Bruce McManus Cardiovascular Biobank, has overseen this program for the last 15 years. As always, the week was made possible thanks to contributions from many HLI labs, staff, and trainees, who helped supervise the students and run activities throughout the week.

“High school science week has been such an important part of the training and outreach programs at HLI. These students are always grateful for the early opportunity to engage in research and learn lab skills. Being part of their learning experience has been a proud and humbling moment. When we hear, “Participation in HSSW has been the greatest highlight of my high school years,” we feel that our jobs are done. We look forward to running this program again in the fall.”

— Dr. Gurpreet Singhera

On April 13th, the Bruce McManus Cardiovascular Biobank and James Hogg Lung Biobank hosted an educational outreach session for students of Douglas College, providing a comprehensive understanding of tissue biobanking and its essential role in advancing cutting-edge research in cardiovascular and lung diseases. The session highlighted the significance of collaborative efforts between academia and the medical community, emphasizing the need to bridge the gap for the betterment of health care.

The aftermath of COVID

Between 5-50% of COVID-19 survivors are estimated to develop long-COVID (LC), which includes diverse symptoms that can last months after the initial SARS-CoV-2 infection. These symptoms can involve the entire body, including the respiratory, neurological, cardiovascular, and gastrointestinal systems, and can be debilitating, greatly affecting the quality of life of individuals with LC and their families. Although the symptoms are well described, the cause of LC remains unclear, and consequently, many patients are undiagnosed and not properly treated. Identification of LC- specific biomarkers is therefore paramount to improving diagnosis and clinical management of the syndrome.

Understanding the current literature

The HLI’s Estefanía Espín, a Ph.D. student in Dr. Scott Tebbutt’s lab, and a Mitacs Accelerate intern at the PROOF Centre of Excellence, recently undertook a scoping review to describe the molecular and cellular biomarkers identified to date with potential use for diagnosis or prediction of LC. A scoping review is a way to present an overview of the large and diverse body of literature surrounding long-COVID research. This review was recently published at eBioMedicine, part of the Lancet Discovery Science series.

Conducted using the Joanna Briggs Institute (JBI) Methodology for Scoping Reviews, Espín, and colleagues, including Dr. Chengliang Yang at PROOF, performed a search in the MEDLINE and EMBASE databases, as well as in the grey literature for original studies, published until October 5th, 2022, reporting biomarkers identified in participants with LC symptoms (from all ages, ethnicities, and sex), with a previous infection of SARS-CoV-2. 

Potential biomarkers for long-COVID

In total, 23 cohort studies were identified, involving 2163 LC patients [median age 51·8 years, predominantly female sex (61·10%), white (75%), and non-vaccinated (99%)]. A total of 239 candidate biomarkers were identified, consisting mainly of immune cells, immunoglobulins, cytokines, and other plasma proteins. The candidate biomarkers compiled in the review point to LC resulting from an uncontrolled immune response, triggered by the initial viral infection, and characterized by specific immune signatures.

“An optimal biomarker should be objectively quantifiable, sensitive and specific, easily adapted into routine clinical practice, and detectable in easily accessible specimens. The pool of candidate biomarkers reported in my review were detected in blood samples and therefore could be established in quantifiable assays for clinical practice.”

Next steps

Given the large number of biomarkers identified, more work is needed to identify those which could be used to stratify risk at SARS-CoV-2 infection onset, confirm LC diagnosis, and/or subset patients for specific interventions. This is work that Estefanía will continue during her Ph.D. project.

“As I continue my Ph.D. project, I will conduct qualitative research to inquire about the perspectives of long-COVID patients and clinicians about their needs in biomarkers research. Thus, the scoping review together with the qualitative research will allow me to have a complete landscape about LC biomarkers resulting in a relevant clinical question to be answered by biomarker development from molecular and cellular data.”

Estefanía Espín, PhD candidate
Dr. Scott Tebbutt’s lab

For full text: Cellular and molecular biomarkers of long COVID: a scoping review Espín, Estefanía et al. eBioMedicine, Volume 91, 104552

Low carb, high fat diets, also called keto diets, have been gaining popularity as a quick way to lose weight.¹ It involves consuming very low levels of carbohydrates, like bread, rice, pasta, and other grains, and high levels of fat, to induce the body into a ‘ketogenic’ state, using fats instead of carbohydrates as the primary energy source.

However, a recent study by Dr. Iulia Iatan, MD, PhD, and physician scientist at the Healthy Heart Program and Centre for Heart Lung Innovation and a postdoctoral fellow under the supervision of Dr. Liam Brunham, showed that a keto-like diet may be associated with increased risk of cardiovascular events such as chest pain, blocked arteries, heart attack, and stroke. Dr. Iatan used data from the UK Biobank, and identified 305 individuals who reported consuming less than 25% of daily calories from carbohydrates, and more than 45% of calories from fats. This is in contrast with strict keto diets that consist of less than 10% carbohydrates and 60-80% in fats.

Compared to individuals who report a more balanced diet, those on a keto-like diet had higher levels of LDL cholesterol, or “bad” cholesterol, which is a known risk factor for heart disease. After more than 10 years of follow up, 9.8% of people on a keto-like diet experienced a new cardiac event, such as artery blockage, heart attack, stroke and peripheral arterial disease, compared to 4.3% of those on a standard diet, representing more than a doubling of cardiovascular risk.

However, not everyone responds to these diets in the same way, and the data relied on an individual’s self-report of their dietary patterns at one point in time, which does not capture information about dietary changes over time. As an observational study, these findings cannot definitively prove that keto-like diets directly cause cardiovascular disease, but highlights the need for further research to understand the risks and benefits of these diets.

This study was presented as a late breaking abstract at the American College of Cardiology Conference, and has been reported on the CNN.

Job Classification:                             Research Technician 3

Job Title:                                            Laboratory Technician

Faculty:                                              Medicine

Department:                                      Centre for Heart Lung Innovation

Divisions:                                            PROOF Centre of Excellence

Full/Part Time:                                  Full-time

Length of Position:                            1 year with the possibility of extension

                                                            Starting April 1, 2023

Funding Type:                                   Grant Funded

Job Summary:

The successful candidate will be responsible for the day-to-day laboratory operations including coordinating, processing and analyzing biospecimens and supply maintenance and ordering for the PROOF Centre of Excellence. Additionally, the candidate will be involved in research and development of new methods, experimental protocol design, sample preparation, instrument optimization for acquisition and analysis, data interpretation and training of personnel.

Work Performed: Work as a team with researchers in different laboratories and hospitals and on different projects. Work will include:

• Processing biospecimens (i.e. blood) as per Standard Operating Procedure (SOP) for integration into the Biospecimen Information Management System biobank (BIMS), including scanning and organization of frozen biospecimens in hospital freezers
• Preparation and coordination of biospecimens for shipping to collaborators and receiving of biospecimen shipments from collaborators
• Shipment of biospecimens to other hospitals or laboratories
• Performing RNA extraction from whole blood using SOP developed for the Qiagen QIAcube laboratory instrument and other protocols
• Planning and performing experiments using  purified RNA samples with assays developed and/or used by the PROOF Centre, including the NanoString Treg and HEARTBiT assays
• Planning and performing experiments using other assays including nucleic acid assays (eg, PCR), Elisa, etc.
• Extracting bio-molecules from biospecimens and performing appropriate QA/QC
• Providing consultation and direct involvement in diverse research projects including data interpretation, trouble shooting for sample preparation, and experimental design
• Developing and updating SOPs, including biosafety protocols
• Maintaining laboratory equipment and inventory of laboratory supplies by creating orders for supplies as needed
• Maintenance of PROOF freezers and the biospecimens contained within
• Training and supervision of other laboratory members in the use of equipment, techniques and procedures
• Writing reports and presenting results at meetings
• General laboratory tasks
• Other duties as required

Consequence error/Impact of Decision

Work requires judgment and initiative.  Errors would have a significant impact on the operation of the laboratory and success of the projects.

Supervision Received:

The position will require minimal supervision and the incumbent will exercise independent judgment regarding scheduling and timely completion of tasks. The applicant will receive supervision from Dr. Scott Tebbutt and Sara Assadian.

Supervision Given:

The applicant will be working with other laboratory members including graduate students, post-doctoral fellows and technicians. The applicant may supervise directed studies/summer students.

Working Conditions:

The laboratory is located at St. Paul’s Hospital in the Centre for Heart Lung Innovation and the netCAD Blood for Research Facility at UBC. The working environment is free of occupational exposures except those which are typical for this type of research and are controlled by standard guidelines.

Personnel Specifications:

University degree in molecular biology/biochemistry or related field or graduation from a technical college or institute PLUS a minimum of 3 years of relevant experience

Experience with independently conducting specialized experiments with assays

Transportation of Dangerous Goods (TDG) Class 7 Receiving Certification preferred
TDG Class 6.2 Shipping Certification preferred

UBC Biological and Chemical Safety Certificates preferred

Effective oral and written communication

Organizational skills are essential

Ability to perform duties with precision, exercise judgment and initiative

Ability to complete assignments in a timely manner

Ability to work independently, once trained and as part of team

Computer experience-MS Office; experience with R/R studio would be an asset

If you are interested in this opportunity please send a cover letter along with your CV to Kelly.ceron@hli.ubc.ca

A Research Assistant position is available with the Providence Health Care (PHC) “Practice-based Research Challenge”. The purpose of this project is to foster and generate research for point-of-care nurses and allied health care professionals who are new to research. The Research Assistant will assist a Research Challenge team in conducting their research.

Heart attacks and strokes are leading causes of death around the world, and many are caused by atherosclerosis, or the buildup of plaque on the walls of blood vessels. The best way to fully understand how atherosclerosis develops and progresses is by studying plaques from human tissues.

Biobanks, or tissue registries, are collections of human biospecimens from the people who consented to donate their aborted tissues for research. For example, the Bruce McManus Cardiovascular Biobank (BMCB) at the Centre for Heart Lung Innovation (HLI) contains over 14,000 cases of specimens from hearts, blood vessels, and other cardiovascular tissues. These specimens were collected from autopsies and cardiac surgeries.

Recent advances in technologies like next-generation sequencing present new opportunities for more in depth studies on the molecular features of atherosclerosis, especially in biobanked specimens. In a review published in Frontiers in Cardiovascular Medicine, Dr. Ying Wang, a Principal Investigator at HLI and Director of the BMCB, led a discussion on how to leverage biobank resources for translational research. From genetic studies supported by large biobanks to proof-of-concept studies that have changed the traditional view of atherosclerosis using only a dozen of biobanked samples, Dr. Wang’s group summarized a few formulas for both basic and clinical scientists to utilize biobank resources.

Dr. Wang’s group also outlines some major roadblocks for translating biobanking research to new biomarkers and therapies for atherosclerosis. These include the lack of bioinformatics or data analysis tools to interpret omics data, especially in the tissue context, as well as the difficulty of making connections between features found in the plaque and blood-based biomarkers, which are more appropriate for clinical testing.

To address these challenges, more collaborations between biobanks and between researchers are needed to link complementary resources and datasets so that results from individual studies can be validated to benefit broader patient populations. Sample collection and storage protocols also need to be updated to ensure that sample quality is appropriate for new downstream technologies and applications. Overcoming these challenges will maximize the utilization of precious human biospecimens, and will reveal important biological information on the underlying mechanisms of atherosclerosis, leading to better therapies and improved outcomes for patients.

Though initially considered primarily a respiratory disease, as the pandemic has evolved, coronavirus disease 2019 (COVID-19) has been increasingly implicated in heart injury. Reports indicate cardiac damage in over 20% of patients, with evidence of direct viral injury, thromboembolism with ischemic complications (circulating clot that causes an obstruction in the blood vessels), and cytokine storm (excessive activation of the immune system).  These patients are at significantly higher risk of dying from COVID-19, but it’s not clear how infection leads to these injuries.

The Bruce McManus Cardiovascular Biobank (BMCB) team (Paul Hanson et al), recently studied the explanted hearts of 21 COVID-19 positive decedents. Using a custom tissue microarray on regions of pathological interest and immunohistochemistry and in situ hybridization, they compared these hearts to clinically matched controls and patients with other causes of viral myocarditis.

The COVID-19 samples displayed signs of direct and indirect viral injury (see figure below), demonstrating the multifactorial nature of COVID-19 injury.

Signs of direct injury included depleted troponin and increased cleaved caspase-3; these markers may be helpful in prognosing and diagnosing COVID-19 heart failure in the future.

Indirect mechanisms of injury, including clots in the arteries and veins, inflammation of the blood vessels, and enhanced blood vessel formation, were unique to the COVID-19 samples, and not observed in other virus-associated heart failure samples.

Other observations included the presence of Neutrophil extracellular traps (NETs) in the heart tissue of all COVID-19 patients, regardless of injury degree, and borderline myocarditis (inflammation without associated injury to the muscle cells of the heart) in 19/21 patients.

This work was highlighted in a feature publication in Laboratory Investigation, with the cover showing the characteristic histopathologic features of COVID-19-associated cardiac injury in critically ill patients.