How the body works – an inside perspective

Movies like Osmosis Jones or Fantastic Voyage are a fictional interpretation of what it would be like to visualize, in detail and from the inside, how the body works. But moving from fiction to science, looking inside the body to see things happening in real time is exactly what Paul Kubes has been doing for the past 30 years. He is now joining Queen’s as the Canada Excellence Research Chair (CERC) in Immunophysiology and Immunotherapy.

As a professor at the Queen’s Cancer Research Institute, Dr. Kubes will leverage real-time, in-vivo imaging techniques to get an inside perspective of how immune cells work to create inflammation in response to both bacterial or viral infections and injury. He spoke to the Gazette about his research program and plans for the future.

What is inflammation?

Inflammation is an immune response to any perturbation or distress of the normal condition of our bodies – anything from concussions to cancer to COVID-19 to heart attacks, immune cells are always trying to solve the problem.

Think of an insect bite. When you get bit, you get injected with some toxins, and probably some bacteria as well – things that don't belong in your body. Soon, you will see a little red welt, which is irritating and itchy. That's your immune system walling off that toxin and making sure that it doesn't spread throughout your body. This is inflammation, and it is critical to contain problems in our body.

Why did you decide to develop imaging techniques to study inflammation?

I was a PhD student at Queen’s in the 1980s when I went to a conference in the U.S. where physiologist Neil Granger (Louisiana State University) talked about trying to visualize how things happened in the body. I thought this was the most amazing thing I had ever heard of! I immediately went to him and decided I wanted to work on this project, and that’s what I did for my post-doc.

We began to use very rudimentary microscopes and try and look at blood vessels and see white cells. At that point, we couldn’t tell what kind of immune cells they were, but we could see that, after a stroke, these cells were moving to the affected part of the brain and causing inflammation.

Over the following 15 years, we started developing methods to visually identify different types of immune cells. We did this by genetically tagging the cells with different glowing proteins, one for each type. Now, we have various techniques and can visualize most cells in the body and how they contribute to – or are impacted by – inflammation.

[Dr. Paul Kubes speaks with a research team]

Dr. Kubes will join Queen’s Faculty of Health Sciences and the Queen’s Cancer Research Institute, building on the university’s research strength in understanding the biological mechanisms of cancer and chronic disease.

How will you apply these techniques to advance cancer studies?

The 2018 Nobel Prize in Physiology or Medicine was awarded to for discovering how we could use our own immune system to fight cancer. Their work established the basis of immunotherapy.

Our group will build on that knowledge and use in-vivo, real time techniques to really understand what happens when cancer patients go through immunotherapy. We want to visualize what's happening real time in a tumour and how we can make each of the immune cells better at killing the tumour without injuring healthy tissue.

We will use experimental models to create inflammation in tumours, learn about the role of each immune cell, and try to educate the immune system to attack tumours in a more efficient and safe way.

Can that knowledge be applied to other health problems?

Yes. For example, advancing our understanding of inflammation can also lead to new insights on what to do when inflammation itself causes problems. Imagine inflammation in your head after a concussion, or after a stroke. Like your skin after an insect bite, your brain will also swell. But that swelling is a problem because the brain is contained inside the skull.

Another project I have been working on, with an international research collaboration, aims to investigate what happens when the liver gets damaged by autoimmune-type reactions, and how to reverse fibrosis. Liver failure can happen for all kinds of reasons, but mostly the result is scarring and fibrosis. If we can somehow work with the immune system to reverse that, it would be a game changer for the way we treat liver diseases.

What does it mean to you to be named a CERC?

It is an unbelievable honor to have received a CERC chair and be part of this incredibly important program allowing researchers to explore the biggest challenges facing humans. I have been studying the immune system for more than 30 years with the overall goal to use its power to fight infections and cancers and help in chronic disease.

How does it feel to be back to your alma mater (Dr. Kubes attended Queen's in the 1980s), now as a professor?

I’m excited! It will be like starting over, and I know I will have good colleagues to work with. Queen’s has a lot of young recruits in the area of immunology and cancer biology, talented cancer researchers at the institute, and a world-renowned cancer clinical trials group. I really look forward to contributing to the team!

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