Dr. Justin Tze Ho Chan: Swimming through immunity—What fish can teach us about the immune system

This issue, we are joined by Dr. Justin Tze Ho Chan, an alumnus of the University of Toronto Department of Immunology, whose research trajectory has been shaped by a curiosity about the immune system of members of the animal kingdom beyond mammals—notably those of the inhabitants of freshwater rivers and lakes. Diving into the world of fish, Justin’s work explores how vertebrates have evolved diverse strategies to fight infections and adapt to their environments. His contributions to the field include work with sea lamprey antibodies, teleost fish immune cells and immunological memory, offering a glimpse into how studying evolutionarily distant organisms can reshape our understanding of immunity in humans.

1. Across your PhD and post-doctoral work, your research has revolved around immunity beyond humans. What first drew you to studying fish immunology?

“The earliest exposure I had to fish immunology was an MIMM314 lecture at McGill University, in 2011. Dr. Roger Palfree introduced us to alternative immunity in the lamprey and the work of Dr. Max Cooper and colleagues, supplemented by a video ‘not for squeamish members of the audience’. Seeing the lamprey, first thing in the morning in a dimly lit lecture hall, was certainly captivating and eye-opening.”

Justin explains how this moment opened the door to a research area where many foundational questions remain unanswered and the thrill of discovery still felt possible: “Studying fish immunology, I feel like an early explorer in uncharted waters, having the chance to study fundamental and basic topics about immunology, like those I was born too late to study in humans.” He adds that he is also drawn to comparative research, as it contributes to a sense of shared biological history: “No matter how uncanny or unfamiliar someone may look, [through the lens of immunology] we all have something in common, we are all related and have a shared history.”

Following this initial spark, he credits his mentors, Drs. Ehrhardt and Tomáš Korytář, for further cultivating his interest. “Stars aligned and I am eternally grateful to have pursued a PhD in the laboratory of Dr. Götz Ehrhardt,” he says. His experience as a graduate student, focusing on lamprey antibody biology, plunged him deep into the depths of fish immunology.

2. How has working with fish changed how you think about human immunology?

“If anything, working with fish has only heightened my appreciation for human immunology.” He adds “it goes both ways,” echoing a sentiment from fellow fish immunologist, Dr. Brian Dixon: “We are all comparative immunologists because without human immunology, there would be nothing to compare to.” Working with fish also reframed how he sees humans within the evolutionary landscape. “It is humbling that we are just one node on a map. Human immunity is also just one alternative immune system in an ocean of alternatives.” He emphasizes that “primitive” species “did not stop evolving as soon as new ones emerged. They are ‘primitive’ in terms of evolutionary distance, but it does not mean that their solution to immunity is featureless or lacking. I think it is just that we are not adapted to the same needs and environment.”

3. For readers who may be unfamiliar, what are some of the key similarities and differences between the human and fish immune systems?

Beginning with the features shared among vertebrates, Justin references how vertebrates evolved from a common ancestor over 500 million years ago. He explains, “It is likely that an evolutionary ‘Big Bang’ gave our ancestors the ability to somatically diversify antigen receptors, the main lymphocyte lineages responsible for cellular and humoral immunity, and compartments within which these cells can develop, or mount responses.”

On the other hand, teleost fish, his current area of study, differ immunologically not only from humans, but between species due to tremendous diversity. “You can have a carp and a salmon whose last common ancestor diverged 200 million years before that of humans and mice, making it challenging to generalize findings from one fish species to another.” However, he highlights temperature dependence and mucosal surfaces as some major differences: “Fish are cold-blooded and temperature drastically impacts their physiology, biochemistry, and behaviour.” He also states, “If you like mucosal immunology, the entire external body of a fish is mucus, from skin to gills to gut, and it is unclear how homeostasis is maintained across all these surfaces.”

4. What advice would you give to students interested in exploring research in organisms beyond humans and mice?

While Justin encourages students to follow their curiosity first and foremost, he argues, “Humans already pay an inordinate amount of attention to humans.” He points to the long history of discoveries made through studying unconventional organisms: “The rich history of immunology is adorned with and in debt to discoveries from non-mammalian and non-conventional models: from Metchnikoff’s starfish, Hoffmann’s fruit flies, back to Cooper’s chickens. Overall, from a One Health perspective, animal health is intertwined with human wellbeing, livelihood, and socioeconomics.”

Justin reassures students that “The field has never been more alive,” and that their “scientific and problem-solving skills will always be transferable to all walks of life.” He adds, “You can see for yourself, the community and support at meetings such as the North American Comparative Immunology Workshop. At the end of the day, we’re all immunologists.”

5. And finally, among the organisms you’ve worked with—humans, fish, or any others—which immune system do you find the most fascinating?

“On the one hand, I have a soft spot for the lamprey because of my upbringing, but also because of my upbringing, any organism with B cells or B-like cells has my admiration.” At the same time, he adds that part of his fascination with lampreys stems from their place in our own evolutionary history, explaining, “It’s a miracle to exist at the same time as lampreys and hagfishes, that we are living descendants of an ancient jawless fish.”

He ends with a sentiment that captures the heart of comparative immunology: “Despite the [evolutionary] distance, immunology prevails… as a tried, true, and refined solution to co-exist with microbes.”

Through his lens, Justin shows us how immunity forms a universal thread connecting vastly different species. His reflections also remind us that the answers we seek to better understand ourselves can be found beyond what is familiar, or in this case, above water.