Dr. Ilker Hacihaliloglu welcomes applications for one fully-funded Ph.D. position in machine learning for lung and heart disease.
The aim of the research project is the development of computational methods, based on machine learning, for managing post-COVID-19 related lung and heart complications, using point-of-care ultrasound imaging. The candidate will be closely interacting with clinicians, scientists, and engineers.
The successful candidate will be based at the University of British Columbia, with research conducted at the Centre for Heart Lung Innovation housed within Providence Health Care’s St. Paul’s Hospital in the heart of downtown Vancouver, British Columbia, Canada. The candidate will be a graduate student at the UBC School of Biomedical Engineering.
Human pluripotent stem cells (hPSCs) harbour enormous potential for regenerative medicine and offer a unique opportunity to advance the development of cell-based therapies. The development of hPSC biobanks, and use of hPSCs in clinical trials, drug screening, and disease modeling, all demand robust stem cell manufacturing and expansion. Although the hPSC manufacturing field is evolving rapidly, a bottleneck is throttling clinical application: existing technologies cannot efficiently scale up production of clinically viable stem cells.
In collaboration with bioengineers at the University of Calgary and with the support from Stem Cell Network of Canada (SCN), Drs. Michael Kallos, Derrick Rancourt, Breanna Borys, and Leili Rohani (a postdoctoral research scientist in Dr. Zachary Laksman’s lab at the HLI) developed a system for bioprocess bioengineering and cell manufacturing of human pluripotent stem cells in a bioreactor to produce clinically viable hPSCs.
Dr. Rohani and her colleagues enhanced stem cell manufacturing by converting hPSCs towards a naïve state (earlier state of pluripotency). This method enabled scalable production of hPSCs and reduced initial culture heterogeneities. Given that the same starting “material” from upstream can be used subsequently to perform downstream experiments, this is a huge advantage for developing clinical cell-based therapies. The breakthrough technique was published in Nature Communications Biology (Rohani L et al. (2020), and covered by several media outlets including The Niche Knoepfler Blog and ESC & iPSC News – STEMCELL Science News.
This work built upon Dr. Rohani’s research on engineered heart tissues in the Laksman lab.
Normal cell-to-cell communication within the heart is essential to orchestrate physiological heart function. In fact, disrupting these communication pathways can lead to heart diseases like atrial fibrillation, a common type of arrhythmia, or irregular heartbeat, that can cause blood clots and stroke. Similarly, other diseases such as cardiac fibrosis, which is linked to inflammation, thickening, or scarring of the heart tissue can also occur as a result of disrupted cell communication.
To study why these disruptions occur in patients with arrhythmia and cardiac fibrosis, Dr. Rohani is working on developing laboratory tissue-engineered models using patient stem cells. These stem cells are collected from patients and can be grown into various types of heart cells, generating a model of the patient’s heart that can then be used for testing therapies.
Dr. Rohani was invited to THE STEM CELL PODCAST. Ep. 201: “The Future of Research” to talk about her research on stem cell bioprocess engineering. During this interview, she discussed the application of engineered heart tissues for cell therapy and advised her peers to be great science communicators, giving the advice that “Number 1 = Networking, Number 2 = Networking, Number 3 = Networking”.
The podcast was featured in the Gladstone Institute News. The Gladstone Institute is one of the world’s leading institutes in the field of cardiovascular disease, leveraging genetic, systems biology, computational, and engineering approaches to study heart disease and stem cell biology. For more information, see: https://gladstone.org/science/cardiovascular-disease-institute
The aorta is the largest artery in the body and connects the heart to the vital organs. In 1 in 100 people, the closest part of the aorta to the heart widens, becoming an aneurysm. In the majority of cases, an aneurysm of the aorta forms when it is weak. People with an aneurysm of the aorta are at risk of sudden tearing of the aorta (aortic dissection), which carries a high death rate. Most people with an aneurysm of the aorta receive regular scans to monitor the size of the aneurysm. Once the aneurysm reaches a certain size – often between 50 and 55 mm – guidelines recommend surgery to replace the diseased part. Sadly, this strategy misses 70% of patients who eventually experience tearing of the aorta.
Dr. Stephanie Sellers, a Principal Investigator at the HLI, and Dr. Alex Fletcher & Prof. David Newby (University of Edinburgh) along with international team members from the University of British Columbia, University of Edinburgh and University of Liverpool, explored whether microscopic calcification, which is formed in areas of the body under stress, could be used as a marker of those with high-risk aneurysms. The team found that in mild aneurysm disease there is a rise in microscopic calcification, but in severe disease – when the aneurysm is very weak – this calcification is lost. The team also demonstrated that this microscopic process could be tracked using a special scan test called a PET scan using a special tracer called 18F-NaF.
“Our study is an important step towards identifying patients at the highest risk of aortic aneurysm disease. Using these PET scans, our hope is to find patients who can be treated with early, life-saving surgery.”
Dr. Stephanie Sellers, Clinical Assistant Professor, UBC, and Principal Investigator at HLI
This study was published in Atherosclerosis Thrombosis & Vascular Biology and featured as the journal cover.
The HLI’s Dr. Tillie Hackett and former PhD Dr. Emmanuel Osei (now Assistant Professor at UBCO) were part of UBC’s joint PhD program – a program that gives candidates who would otherwise never have had the chance, an opportunity to become leaders in their fields.
The program is essentially a partnership arrangement between UBC and other universities around the world, designed to share doctoral candidates, and the costs, as candidates work towards earning their PhD. Following two years at the University of Groningen, the Netherlands, Dr. Osei moved to Vancouver to join Dr. Hackett’s lab at the UBC Centre for Heart Lung Innovation to investigate factors that play a role in asthma.
People applying for this opportunity are very motivated, highly qualified students. These people wouldn’t have this opportunity otherwise to pursue what they love: research.
Dr. Tillie Hackett
Their story was recently highlighted by the UBC Vice-Provost International: https://global.ubc.ca/news-events/stories/may-25-2022-globetrotting-phd-no-other
HLI’s Strategic Plan 2022-2027 was developed in collaboration with Providence Research, UBC Faculty of Medicine, Providence Health Care and Simon Fraser University Faculty of Health Sciences. Over the next few years, our vision is to discover solutions to improve the heart and lung health of peoples of British Columbia, Canada and throughout the world. To accomplish this, we will attract, support, and connect world class researchers to discover patient-centred therapeutic and biomarker solutions to improve cardiovascular and respiratory health by focusing on three core areas: research, education, and knowledge mobilization.
Cardiovascular events like heart attack and stroke account for almost 20% of all deaths in Canada. Many of these events are caused by “vulnerable plaques” that have built up on blood vessel walls. These plaques are susceptible to triggering large clots and blockages in blood vessels, leading to heart attack and stroke. While some plaques share common structural features like a thin cap and large core, not all plaques look the same, and distinguishing between vulnerable and stable plaques remains a puzzle.
To develop a better method to identify vulnerable plaque and at-risk patients, Dr. Ying Wang and the team, including Dr. Clint Miller (University of Virginia, USA), and Dr. Amrit Singh (HLI), was recently funded by the New Frontiers in Research Fund to convert omics data, which is the molecular information of the plaques, into visible image pixels of plaques. This will allow the researchers to characterize the biological processes that are happening in each specific region of the plaque.
The findings from this project will be particularly important for females, who are less likely to have vulnerable plaques with thin caps and large cores compared to males, making these plaques especially difficult to identify and treat. Our study will reach this high-risk population that has not been well studied by prior research because of biases in sample selection and lack of interdisciplinary communication.
“This project is an exciting new collaboration that is right at the interface of bioinformatics and digital pathology. It will be the first step towards our longer term goal of identifying patients who are at high risk for cardiovascular events.” – Dr. Ying Wang, Assistant Professor, UBC Pathology and Laboratory Medicine and Centre for Heart Lung Innovation
Many patients with breast and other types of cancer are treated with a chemotherapy drug called doxorubicin, but this drug has many side effects, including heart failure. This “doxocubicin-induced cardiotoxicity”, or DIC, can affect up to a quarter of all patients who are treated with doxocubicin, but it is not clear why it affects some patients but not others.
Dr. Liam Brunham and his group previously discovered that patients with a mutation in the RARG gene are more susceptible to DIC. To better understand how RARG is involved in DIC, they used a patient-derived stem cell model and discovered that this RARG mutation leads to defects in DNA repair after exposure to doxorubucin.
This discovery could help physicians identify which patients are at risk of DIC to provide alternate treatment strategies, or improve monitoring and screening protocols to prevent patients from developing life-threatening heart damage after cancer treatment.
Read the full paper published in Stem Cell Reports.
