U of T researchers show how a protein found in cardiac muscle helps prevent heart failure

Researchers at the University of Toronto have found that a receptor expression-enhancing protein contributes to normal heart development and function by regulating the sarcoplasmic reticulum, a network of tubules found in cardiac muscle cells.

The sarcoplasmic reticulum is key in the development and progression of heart disease, governing biochemical changes, structural remodeling and deterioration. But how this membrane-bound system organizes itself is still mostly unknown – especially in cells with a highly differentiated or diverse network such as heart muscle cells, or cardiomyocytes.

“Our findings show that a protein called REEP5 plays a critical role in regulating cellular stress responses in heart muscle cells,” says Frank Shin-Haw Lee, a PhD student in the lab of Anthony Gramolini, an associate professor of physiology in U of T’s Faculty of Medicine who is based at the Ted Rogers Centre for Heart Research.

“When REEP5 is depleted, it destabilizes the heart and reduces the amount of blood the heart can pump on each contraction,” says Lee. “When we removed this protein in both mice and zebrafish, it distorted the structure and shape of cardiomyocytes and led to cardiac dysfunction.”

The journal Nature Communications published the findings this week.

When cardiomyocytes are under sustained stress from general dysfunction or disease, cellular pathways through the sarcoplasmic reticulum can lead to cell death and heart failure. Lee says that REEP5 is vital to the formation of the sarcoplasmic reticulum and to how it responds to stress and regulates calcium, which is essential for heart health.

A better understanding of how REEP5 functions in the heart may elucidate how heart failure develops amidst a sarcoplasmic reticulum in stress, Lee says.

The Gramolini lab worked with several other Toronto researchers on the study, including Ian Scott, a professor of molecular genetics at U of T and a senior scientist at the Hospital for Sick Children. The work builds on previous collaborative research from the labs of Gramolini, Scott and medical biophysics professor Thomas Kislinger in 2015, which created a blueprint of critical cell-surface and membrane-associated proteins in the heart.

Medical student Sina Hadipour-Lakmehsari was a co-first author on the current paper with Lee, and he says the findings may provide insight into heart disease in patients.

“It is clearly an important protein for cardiac development and function and, combined with future human studies, it may help us unearth new potential therapies,” Hadipour-Lakmehsari says, adding that the lab can continue to look at REEP5 in genetic studies to help shed light on diseases whose causes remain unknown.

“This study is among the first in the world to show that the REEP5 protein plays an essential role in the stress responses that often lead to heart failure,” adds Gramolini, who is also a scientist at Toronto General Hospital Research Institute, University Health Network. “Deciphering the complex layers of heart function on a cellular level will help us generate new therapeutic and preventative strategies for heart failure.”

The study received support from the Ted Rogers Centre Innovation Fund, the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research, among others.

#UofTGrad16: the doctors are in

lanthierj — Tue, 31 May 2016 17:41:53 +0000

#UofTGrad16: the doctors are in

lanthierj Tue, 05/31/2016 - 13:41

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(graduation photos by Johnny Guatto)

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“From the first baby I helped bring into the world to the resilience I saw in the eyes of a dying man, these are memories that I will cherish for the rest of my life”

They just graduated from the top medical school in Canada –12th in the world – and somehow they made it look easy.

Students from the Faculty of Medicine became the first to graduate from the University of Toronto's 18,000-strong Class of 2016 today, crossing the stage at Convocation Hall to receive their medical degrees.

They're among an expected 13,500 students who will graduate with undergraduate and graduate degrees at spring convocation ceremonies that continue through June 15.

See a Storify from the May 31 ceremony

But just who are great minds rocking the black gowns?

Below, meet some of the newest doctors who'll be caring for patients and leading research for years to come.

Erik Yao:

Next steps: residency in family medicine at U of T.

Why: “I hope to follow that up with additional training and/or locum work in particular areas of interest such as palliative medicine. Down the road, I want to work in a community-based practice that allows me to integrate my subspecialty interests and also pursue health advocacy.”

Favourite memories: “I’ve had so many meaningful encounters with patients. From the first baby I helped bring into the world to the resilience I saw in the eyes of a dying man, these are memories that I will cherish for the rest of my life. They’re a constant source of inspiration and drive for me to become a better physician.”

Louai Musa:

Next steps: family medicine residency (in Abbotsford, BC) then practice in under-resourced areas.

Why: “My family is originally from Palestine. I think about people who are just as smart, just as hard working, but didn’t end up where I did. When I think about those inequities and injustices, I know it’s my responsibility to give back. “I want to help build better health-care systems in Canada and abroad. I want to go to the places where people aren’t heard, and help them.

Favourite memories: working with a U of T student group to change practices of the Toronto Police Department around sharing information related to mental health.

“Even when there was no harm to others– such as in a suicide attempt – if the police were involved, that information would be included in records that were accessible to the U.S. border police.

“I could see the impact of this during my psychiatry rotations. Patients were sometimes unwilling to discuss their mental health issues because they were fearful of the police being told and having this permanent mark on their record. It was important for me to do something about it.”

Jamal Depradine:

Next steps: residency in internal medicine in Ottawa then train as a cardiologist.

Why: “I want to be a physician that makes a substantive impact.

“People think that doctors doing community work need to be in family practice or in public health. But if those are your fundamental values, you will find a way to incorporate them into whatever you do. People in the lowest income percentile are much more likely to die of cardiovascular disease. So there’s a lot of work to do in cardiology. I think all physicians regardless of specialty need to look at social principles as their fundamental responsibility.”

Favourite memories: In 2004, Depardine took part in the Summer Mentorship Program (SMP), which brings Indigenous and Black high school students to U of T to explore the health sciences and meet faculty and alumni working in hospitals and clinics.

“Where I grew up in Scarborough, there weren’t many people who were involved in the medical professions. During SMP, I started envisioning myself in these professional positions.”

After earning a BSC in physiology at U of T and a Master of Management and Innovation from U of T Mississauga, Depardine enrolled in the MD program. He conducted research with the Street Health Nursing Foundation, working on projects to improve the quality of service for under-housed populations.

“I feel that the fundamental ethos of medicine is to identify suffering and vulnerable people and to do the most I can to address their suffering and vulnerability.”

Eric Coombes:

Next steps: residency in internal medicine.

Why: “Internists unravel diagnostic complexity and manage disease across a wide spectrum of acute and chronic illnesses, while simultaneously communicating with our patients empathetically and advocating for their needs across the interdisciplinary team.”

Favourite memories: “My favourite experiences in medical school were my clerkship rotations, where you really get the first opportunity to apply the medical knowledge you have acquired to direct patient care.

“It was fascinating to be exposed to such a diversity of clinical presentations and it was gratifying to develop longitudinal relationships with my patients.”

Kim Blakely:

Next steps: residency in dermatology.

Why: “The breadth and complexity of diseases in dermatology, and the way they impact patients, not only physically, but also mentally and emotionally, really resonated with me. I also love that being a dermatologist allows you the flexibility to be an internist, a surgeon, and a pathologist all within a single day, and I think that is something very unique and special to dermatology.

“I see myself establishing a practice as an academic dermatologist and pursuing a blended career that includes medicine, research and teaching. I have a particular interest in cancer, which stems largely from my PhD in oncology research, and I could see myself continuing to further explore and develop this as I progress in my career.

“I also appreciate the valuable role that dermatologists play in the community and I see myself becoming involved in initiatives to improve e-health technologies to increase access to dermatologic services in underserved areas.”

Favourite memories: “I think my fondest memories come from clerkship, the time when students finally become immersed in patient care and we get our first taste of what being a doctor truly feels like. I’ve met so many wonderful patients and these experiences have really helped shape the person I am today.”

U of T Medicine

U of T researchers show how a protein found in cardiac muscle helps prevent heart failure

#UofTGrad16: the doctors are in

See a Storify from the May 31 ceremony

Erik Yao:

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Louai Musa:

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Jamal Depradine:

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Eric Coombes:

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Kim Blakely:

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