不良研究所

Prof. Terry H茅bert is noticeably upbeat these days, and for good reason.聽聽

Thanks to a generous $1.6-million boost from the Fondation Courtois, the Department of Pharmacology and Therapeutics is now home to a state-of-the-art microscope that will play a pivotal role in research on dilated cardiomyopathy (DCM).聽聽

DCM is a condition in which the heart's chambers stretch and become thin, leading to a decreased ability to pump blood. The most common causes of DCM can be genetic or through exposures to chemotherapeutic drugs used to treat cancer. Complications can include heart failure, arrhythmias, blood clots and an increased risk of complications during pregnancy. Recent figures show heart failure affects over 600,000 Canadians, and close to 50% of patients with DCM die within five years.聽

With the addition of the Revvity Opera Phoenix microscope, a versatile platform for high-content screening and analysis, which gives researchers the ability to study complex biological systems and identify potential drug candidates, H茅bert expects that it will be possible to model disease in individual patients, allowing targeted treatment.

In partnership with聽heart failure specialist Dr. Nadia Giannetti (MDCM鈥�91) at the Research Institute of the 不良研究所 Health Centre (RI-MUHC), H茅bert leads the Heart-in-a-Dish project, which is aimed at personalizing and improving the understanding and prevention of heart conditions, particularly DCM. It involves growing patient heart tissue in Petri dishes to create a disease-in-a-dish model.

The project, which is part of the larger 不良研究所 Cardiomyopathy Initiative, launched in 2020 with the help of an initial $3-million commitment from the Fondation Courtois to fund five years of research in H茅bert and Giannetti鈥檚 labs to better understand and treat cardiomyopathy using patient-derived stem cell and organoid models. 不良研究所 Health Centre cardiac surgeon Dr. Renzo Cecere (BSc'86, MDCM'90, PGME'97) is part of the effort as well, converting patient blood samples into stem cells.

The project complements the Courtois Cardiovascular Signature Study, a 10-year research project co-led by Giannetti at the MUHC's Glen campus, which is collecting biological materials, MRI imaging and clinical data from participants, and seeks to understand all the factors that contribute to heart disease using artificial intelligence to puzzle out previously undetected patterns.

鈥淭his is big news,鈥� says H茅bert. 鈥淔or example, when we take blood from a person with a cardiomyopathy and make muscle cells from the stem cells, they have the features of the patient鈥檚 disease. The experiments that we do require a type of microscope that can capture information from hundreds of thousands of cells simultaneously and can integrate that into a very rapid analysis of what鈥檚 going on in that patient. That鈥檚 part of the game changer, being able to model disease in individual patients.鈥澛�

The new microscope captures images and analyzes them in ways that provide researchers with previously unattainable information. 鈥淚nstead of getting an overall global response, it allows us to observe what we're measuring and actually track the response down to each cell in the dish, and we can look at the effects of therapies on individual cells,鈥� H茅bert explains.聽

Up until now the management of heart disease has been a one-size-fits-all approach where every patient receives medication in the same order and at the same doses. But as H茅bert points out, men and women may be different in how they experience the disease. 鈥淲e do see differences between male and female patients. We see clear differences between patients and control subjects, and I think that is going to feedback on their care at some point. We can now say to a patient, look at your cells and how they differ from our control subjects. We can see clear differences in how the cells respond to normal physiological stimuli and how they respond to therapeutic interaction.鈥澛�

Therapy testing will allow researchers to experiment with medication in different orders, doses and combinations. 鈥淯sing our cellular models as a surrogate for the patient, we can test these things in cells from the patient without having to subject them to a trial-and-error process, and then potentially suggest treatment to the cardiologist,鈥� H茅bert notes.聽

Giada Castagnola (BSc'23, MSc'25), a graduate student in the Department of Pharmacology and Therapeutics and Heart-in-a-Dish researcher, points out that drug treatment is a major challenge in the clinical field in general and that the Revvity microscope allows researchers to speed up the research process. 鈥淲e can now use patient-derived cells, which allows us to automate and gather data in a short amount of time and automate a pipeline with less human error. We no longer have to sit at a computer and analyze one sample at a time thanks to the software on this microscope. We just build a pipeline and methodically gather data on all cells across experiments. I think that's something that will continue to help us advance in our research.鈥澛�

Heart-in-a-Dish has partnerships with pharmaceutical companies that have recognized the value of these new testing methods and see the advantage of working with researchers to develop uses for their biosensors, says H茅bert. 鈥淲e have started a collaboration with two companies where we're actually testing their biosensors for different disease indications using this microscope. It's really scaled into a centrepiece of a lot of our ability to interact with many different stakeholders, right from patients up to big pharma. It's given us some ground to occupy and people see us.聽 So, pharma understands the value of these models. Most companies are now moving into technologies such as stem cells and derived tissues. Drug companies realize they need people who do disease modelling in human samples and human tissues, so they're turning to programs like ours to connect.鈥澛�

In the early days of drug development, scientists had to translate their findings from animal studies to human biology, but many failed: while they worked well in animals, they failed in humans. 鈥淲e think that there's some use for the technologies and for the approaches that are tied to this microscope that will allow us to do a lot of earlier drug discovery work in human-relevant models,鈥� H茅bert says.

With files from Mark Witten for FMHS Focus.