IMS Magazine Spring 2025 - Inflammation and Allergy

THINK. LEARN. DISCOVER.

SPRING 2025

Inflammation and Allergy

Leading the Future in Kidney Care, Scientific Discovery, and Youth Mentorship Dean Lisa Robinson’s Ever-Growing Spheres of Influence

From Vulnerability to Visibility

Inflammatory Rheumatic Disease

The Pandemic’s Impact on Autoimmune Communities

Revolutionizing Diagnosis, Treatment, and Management Through Advanced Imaging Student-led initiative

IN THIS ISSUE Letter from the Editors................................... 3 Director’s Message........................................ 4 Contributors................................................... 5 Infographic..................................................... 8 Features....................................................... 10 BMC Showcase............................................ 20 Viewpoints................................................... 22 Student Spotlight......................................... 34 Alumni Spotlight.......................................... 36 Faculty Spotlight.......................................... 38 Diversity in Science..................................... 40 Book Review................................................ 42 Travel Bite.................................................... 43 IMS Events................................................... 44 Raw Talk....................................................... 46

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MAGAZINE STAFF EDITORS-IN-CHIEF: Kristen Ashworth Suraiya Mangra Kyla Trkulja EXECUTIVE EDITORS: Kevan Clifford Kiko Huang Alyona Ivanova Nayaab Punjani Lizabeth Teshler SOCIAL MEDIA TEAM: Lizabeth Teshler (Director) Lielle Ronen Abigail Wolfensohn JOURNALISTS & EDITORS: Aria Afsharian Tesam Ahmed Jasmine Amini Gabriela Blaszczyk Tiffany Chien Sara Corvinelli Anthaea-Grace Patricia Dennis Karen Fang Mia Feldman Sreemoyee Ghosh Grace Gibson Katherine Guo Kanak Gupta

Rachel Lebovic Josephine Machado Mahmudul Mannan Anna Mouzenian Lielle Ronen Steven Shen Hania Siddiqui Selina Tang Kowsar Teymouri Priya van Oosterhout Beatrix Wang Emily Wiljer Abigail Wolfensohn Saleena Zedan PHOTOGRAPHERS: Katherine Guo Nancy Kim DESIGN EDITORS: Stefanie Jinyin Wang (CoDirector) Nichole Zhou (Co-Director) Emily Huang Yu-Wen Jan Lauren Jones Jeah Kim Anaiah Reyes Bonnie Wang

FEATURE INFOGRAPHIC

By Bonnie Wang, MScBMC Candidate (2T5)

Copyright © 2023 by Institute of Medical Science, University of Toronto.

All rights reserved. Reproduction without permission is prohibited.

The IMS Magazine is a student-run initiative. Any opinions expressed by the author(s) are in no way affiliated with the Institute of Medical Science or the University of Toronto.

COVER ART

By Lauren Jones, MScBMC Candidate (2T5) FOLLOW US ON SOCIAL MEDIA! www.imsmagazine.com @IMSMagazine @IMSMagazine

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LETTER FROM THE EDITORS

Letter from the EDITORS Welcome to our Spring 2025 issue of the IMS Magazine!

In true Canadian fashion, we endured a harsh, snowy winter. I think we can all agree that the arrival of warmer weather is particularly welcomed this year. What follows suit with blooming tulips and a visit from the Easter Bunny, however, is the not-sodesirable–yet just as emblematic–signs and symptoms of spring: sneezing, a runny nose, and unbearably itchy eyes. Ah yes, allergy season. And for those with chronic inflammatory conditions such as eczema, rheumatoid arthritis, and autoimmune disorders, a seasonal shift can further exacerbate inflammation.

In this issue, we put inflammation and allergy under the microscope–something many of the researchers featured here do in a literal sense. We are excited to showcase an exceptional group of IMS faculty members contributing groundbreaking work in the world of inflammatory disorders: Dr. Amanda Boyle, who is investigating the new potential of neuroinflammation as an early diagnostic marker for neurodegenerative disease; Dr. Benjamin Steinberg, who is unlocking the secrets of cell rupture to pave the way for new treatments for inflammation-induced cell death; Dr. Lihi Eder, who is revolutionizing the treatment of inflammatory rheumatic disease through advanced imaging techniques; and, Dr. Andrea Knight, who is reimagining our approach to mental health care for patients with childhood-onset lupus. In the realm of allergy, we highlight the work of Dr. Julia Upton, who is looking beyond avoidance to treat food allergies by identifying predictive and patient-specific allergy markers.

This issue, we are honoured to spotlight Dr. Lisa Robinson, Dean of the Temerty Faculty of Medicine and Clinician-Scientist at The Hospital for Sick Children. We highlight her innovative research in kidney inflammation and her trailblazing academic and career journey that led to her historic appointment as the second female Dean of the Faculty of Medicine at the University of Toronto. In addition, our IMS Alumni and Student Spotlights feature Dr. Mikaeel Valli and Stefan Aguiar, both of whom have made a lasting impact on IMS and the community more broadly. Our Viewpoint articles for this issue explore inflammation and allergy as it relates to our world in 2025: the rise of mast-cell instability in the post-COVID-19 era; the growing impact of our climate and environment on immune conditions and aging; and the latest treatments on the verge of breakthrough, including CBD for inflammation, micro-dosing for allergies, and anti-inflammatory eating for longevity.

As always, thank you to our incredible team of journalists, editors, and designers at the IMS Magazine for their hard work and dedication in bringing this issue together.

We hope you enjoy the read, and all the rest of the blossoming joy that springtime brings (with some good ol’ antihistamines in the back pocket).

Kristen Ashworth

Kristen is a PhD student studying the use of a human-based retinal organoid model to investigate cell therapies for genetic eye disease under the supervision of Dr. Brian Ballios at the Krembil Research Institute. @K_Ashworth01

Suraiya Mangra

Suraiya is a 2nd year MSc student investigating the effects of neuromodulation interventions on brain morphology in patients with neurodegenerative disorders at the Krembil Research Institute under the supervision of Dr. Andres Lozano.

Kyla Trkulja

Kyla is a PhD student studying the mechanism of action of novel therapies for lymphoma under the supervision of Dr. Armand Keating, Dr. John Kuruvilla, and Dr. Rob Laister. @kylatrkulja

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY |

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DIRECTOR’S MESSAGE

DIRECTOR’S MESSAGE

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s the days stretch and the clocks lean forward, an undeniable whisper of Spring fills the air. However, with the season’s renewal comes the onset of allergy season, seamlessly aligning with the theme of our Spring 2025 issue of the IMS Magazine, which focuses on Inflammation and Allergy.

Photo Credit: Mikaeel Valli

DR. MINGYAO LIU Director, Institute of Medical Science Professor, Department of Surgery Senior Scientist, Toronto General Hospital Research Institute, University Health Network

This edition highlights the pioneering work of our distinguished IMS faculty whose research is advancing the frontiers of diagnosis and treatment for inflammatory conditions. Dr. Benjamin Steinberg is delving into the complexities of inflammatory cell death and exploring therapeutics to inhibit pro-inflammatory cascades following cell rupture. Dr. Amanda Boyle is examining the dual nature of neuroinflammation and exploring its role in perpetuating neurodegenerative disease and gliomas while also evaluating its potential as a tool for early diagnosis. Dr. Lihi Eder is utilizing ultrasound imaging to allow for better detection and screening of psoriatic arthritis and co-morbid cardiovascular disease. Dr. Andrea Knight is researching the cognitive deficits and mental health complications associated with childhood-onset lupus and potential interventions to be implemented in practice. Lastly, Dr. Julia Upton is investigating food-borne allergies and exploring innovative methods to improve tolerance, moving away from the conventional practice of strict avoidance.

In addition to the feature on research, we also want to turn the spotlight on three remarkable individuals within the IMS community who have made significant contributions both to the department and the broader university. Dr. Lisa Robinson, who has recently assumed the role of Dean of the Temerty Faculty of Medicine, is celebrated in this issue for her inspiring research journey and impactful leadership.

Stefan Aguiar, our current Co-President of the IMS Students’ Association (IMSSA), shares his leadership experiences and reflects on how his role has enriched his growth as both a researcher and an individual. We also hear from Dr. Mikaeel Valli, former Editor-in-Chief of IMS Magazine, who offers insights into his experiences as a recent graduate of IMS and his transition into the industry. Additionally, this issue provides a glimpse into the memorable moments from this year’s Winter Party, where students and faculty gathered for an evening of camaraderie, food, dancing, and festivities.

On behalf of the IMS community, I extend my warmest congratulations to the new faculty joining IMS and members who have received promotions this year. I would also like to thank the Editors-in-Chief—Kyla, Kristen, and Suraiya—as well as the dedicated journalists, editors, photographers, and design team for their exceptional work in bringing this issue of the IMS Magazine to life. I hope you find inspiration in reading about the extraordinary achievements of our community!

Sincerely, Dr. Mingyao Liu Director, Institute of Medical Science

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CONTRIBUTORS

Contributors Aria Afsharian is a first-year MSc student at St. Michael’s Hospital under Dr. Andras Kapus. His research focuses on cell biology, specifically the role of signalling proteins in the antiviral immune response.

Apart from the lab, Aria enjoys drawing, reading and working out.

Jasmine Amini is a first-year MSc working under the supervision of Dr. Daphne Korczak at the Hospital for Sick Children. Her research interests lie in social media use and family functioning among youth with an acute self-harm or suiciderelated concern. Outside of academia, Jasmine enjoys reading, volunteering, and exploring Toronto. jasmine_amini9

Tiffany Chien is a PhD student in the Department of Medical Biophysics working at the Mouse Imaging Centre. Under the supervision of Dr. John Sled & Dr. Jason Lerch, her research aims to investigate how maternal autoantibodies affect offspring brain and behavior development. She is also a science writer for RawTalk Podcast.

In her free time, she enjoys reading, baking, playing board games & building LEGO, and being outdoors with her husband and dog. tiffanycblum

Graphic design by Nichole Zhou

Spring 2025

Kevan Clifford is a PhD student in the IMS program, with a cross-appointment at the Centre for Addiction and Mental Health.

Working under the supervision of Dr. Yuliya Nikolova, his research combines bioinformatics and neuroimaging to characterize mechanisms of brain aging at the genetic level, and outcomes on brain structure and function. Outside of the lab, Kevan enjoys trail running, photography, and a good book (preferably while curled up with his cat, Rauru).

Sreemoyee Ghosh is a PhD student working under the supervision of Dr. Vinod Chandran at the Krembil Research Institute. Her research focuses on identifying novel markers and pathways for psoriatic disease using multi-omics integration. In her free time, she loves painting, exploring different cuisines and places in Toronto with friends, watching TV shows and reading a good book.

Sara Corvinelli is a first-year PhD student supervised

by Dr. Jacques Lee at the Schwartz/ Reisman Emergency Medicine Institute.

Her thesis is exploring innovative ways to improve delirium recognition for older people who seek emergency care. When she’s not researching, Sara enjoys ballet, listening to film scores, nature walks, volunteering and time with loved ones. saracorvinelli

Mia Feldman is a first-year MSc student working under the supervision of Dr. Isabella Caniggia at the Lunenfeld Tanenbaum Research Institute. They are studying the molecular origins of preeclampsia with emphasis on maternalplacental crosstalk in the disease. In their free time, Mia enjoys reading and exploring different neighborhoods in Toronto!

Grace Gibson is a first-year MSc student in the Biomedical Communications program studying to become a medical illustrator. She aims to work in patient-facing media and outreach focused on the LGBTQ community. In her free time, Grace enjoys reading books and painting.

Katherine Guo is a first-year MSc student working under the supervision of Dr. Shannon Lange at the Centre for Addiction and Mental Health. Her work focuses on patterns of alcohol consumption and its related harms, aiming to better-understand the association between alcohol consumption and suicide mortality.

Outside of her academics, Katherine spends her time working on various graphic design projects, taking photos, and exploring the wildlife in and outside of the city. Katherine is also a part of our photography team!

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY |

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CONTRIBUTORS

Kiko Huang is a second-year MSc student, currently studying glaucoma through an epidemiological lens under the supervision of Dr. Yaping Jin. Her work aims to investigate various trends in ophthalmology and vision care to gain a better understanding of the health landscape and guide policy. During her free time, she’s likely out exploring all the food that the city has to offer (recommendations appreciated)! kikohuangs

Rachel Lebovic is a first-year PhD student at Sunnybrook Health Sciences Centre under the supervision of Dr. Mark Sinyor. She is studying suicide prevention through popular media as a tool to teach mental health literacy to youth. She also has an interest in public mental health and the experience of transitional-aged youth in the mental health care system. Outside of research, Rachel enjoys cooking, going for walks, and building Lego. rachel.lebovic

Alyona Ivanova is a PhD student investigating the molecular signature of glioblastoma using spatial -omics technologies at the Hospital for Sick Children under the supervision of Dr. Sunit Das. Alyona is a professional figure skater and a model.

Alyona is a creative content manager of Panoramics - A Vision. She enjoys traveling, cooking, and reading. _alyonaivanova_

Nancy Kim is a first-year MSc student under the supervision of Dr. Amanda Boyle at the Center of Addiction and Mental Health. Her research focuses on neuroinflammation in different brain tumours originating from glial cells. She uses PET neuroimaging and histology studies to quantify neuroinflammation for early diagnosis and staging of these tumours. Outside of her research, she enjoys playing volleyball, exploring restaurants (mostly ramen places) and cafes (especially for matcha) near campus. Nancy is also a member of our photography team!

Josephine Machado is a firstyear MSc student working under the supervision of Dr. Andrea Knight at The Hospital for Sick Children. Her research is focused on examining the neuropsychiatric impacts of childhood-onset systemic lupus erythematosus (cSLE) through the study of brain-aging in children with the condition. Outside of research, Josephine enjoys reading, playing the piano, nature walks, and volunteering.

Anna Mouzenian is a first-year MSc student working under the supervision of Dr. Victor Tang and Dr. Daniel Felsky at the Centre for Addiction and Mental Health.

Anna is investigating the use of wearable devices to predict outcomes for substance use disorders. In her free time, she enjoys dancing, hiking and pilates. anna.violet

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Nayaab Punjani is a PhD student working under the supervision of Dr. Michael Fehlings at the Krembil Research Institute, University Health Network. Her research is examining a neuroprotective drug therapy for cervical-level traumatic spinal cord injury. Beyond lab work, she works as a TA and residence don, and she enjoys digital art and nature photography in her free time. nayaab_punjani

Lielle Ronen is a first-year MSc student in Dr. Andrew Sage’s Lab at the Latner Thoracic Surgery Research Labs in PMCRT. Her research investigates smoking damage in donor lungs to improve post-transplant outcomes using Ex-Vivo Lung Perfusion (EVLP). Aside from research, she loves painting, baking, running and trying local restaurants in Toronto. Lielle is also a member of our social media team!

Steven Shen is a first-year MSc student working under the supervision of Dr. Sun-Ho Lee and Dr. James Conner at Mount Sinai Hospital. Currently, Steven is working to investigate the microscopic and microbial predictors of Crohn’s disease recurrence after surgery. In his free time, he enjoys spending time on the badminton courts or trying out new food spots around the downtown core. _stevensshen

CONTRIBUTORS

IMS Design Team

Kowsar Teymouri is a third-year PhD student working under the supervision of Dr. James Kennedy at the Centre for Addiction and Mental Health (CAMH).

Kowsar is investigating the role of the immune system genes in schizophrenia and how they are associated with different subgroups of schizophrenia. If not at CAMH, you can find Kowsar running along the lakeshore, creating content for her travel blog, hiking in new trails or painting. kowsar_teymouri

Priya van Oosterhout is a firstyear MSc student working under the supervision of Dr. Yuliya Nikolova at the Centre for Addiction and Mental Health (CAMH).

Priya is investigating how substance use disorders affect the way in which the brain ages, as measured by MRI data. In her free time, she enjoys trying new food, watching movies, or going on hikes. priya.vo

Emily Wiljer is a first-year MSc student working under the supervision of Dr. Daniel Felsky at the Centre for Addiction and Mental Health (CAMH). Emily is investigating a biopsychosocial approach to cognitive resilience, as well as genetic and epigenetic factors in longevity. In her free time she enjoys reading, going to the gym, and trying new restaurants. emily.wiljer

Graphic design by Nichole Zhou

Abigail Wolfensohn is a first-year MSc student in Dr. Mojgan Hodaie’s lab at Toronto Western Hospital. She is researching how the brain’s waste-clearance system functions in people with trigeminal neuralgia, a chronic facial pain condition. In her free time, she enjoys outdoor activities, puzzles, trying new restaurants, and playing the piano. Abigail is also a member of our social media team!

The IMS Design Team is a group of second year MSc students in the Biomedical Communications (BMC) program. Turning scientific research into compelling and effective visualisations is their shared passion, and they are thrilled to contribute to the IMS Magazine.

Stefanie Wang (Co-director) stefaniejyw

Nichole Zhou (Co-director) niczhouart nicholezhou.com

abbywolfen

Copy Editors Tesam Ahmed Gabriela Blaszczyk Anthaea-Grace Patricia Dennis Karen Fang Kanak Gupta Mahmudul Mannan Hania Siddiqui Selina Tang Beatrix Wang Saleena Zedan

Social Media Team Lizabeth Teshler (Lead) is a PhD student supervised

by Dr. Brian Feldman at The Hospital for Sick Children. Her research investigates how to improve the clinical examination of musculoskeletal health for people with Hemophilia.

Outside of research, she loves biking, spending time outdoors and exploring new cities.

Emily Huang emilyhuangart

Yu-Wen Jan dinosaur.visuals

emilyhuang.ca

yuwenjan. myportfolio.com

Lauren Jones

Jeah Kim

lauren.sciart

fabulaurora

linkedin.com/in/ lauren-jones-sciart

fabulaurora. myportfolio.com

Anaiah Reyes

Bonnie Wang

areyes_visuals anaiahreyes. myportfolio.com

visualsbywang bonniewang.ca

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY |

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INFOGRAPHIC

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Compiled by Nayaab Punjani

INFOGRAPHIC

Graphic design by Bonnie Wang

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY |

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FEATURE

From Rupture to Recovery:

The Fight to Control Inflammatory Cell Death

By Steven Shen

D

id you know that over one million cells die every second throughout the human body?1 Fortunately, the immune system helps maintain balance by clearing away these dead cells while also defending against infections and harmful invaders like bacteria and viruses. A critical piece of this puzzle is understanding the molecular mechanisms of cell death and their regulatory effects on inflammation; as well as uncovering how our body and brain may respond to injuries. Cell death occurs in various ways, which include: 1–apoptosis, an essential and programmed form of cell death; 2–necrosis, an uncontrolled form of cell death, often triggered by injury; and 3–pyroptosis, a highly inflammatory form of cell death that releases damageassociated molecular patterns (DAMPs) to amplify inflammatory responses.2 DAMPs are molecules released by damaged cells to help with repair and to assist in restoring homeostasis. However, DAMPs can also often contribute to inflammation and disease. Specifically, pyroptosis is of interest in the field of cell biology, as the release of DAMPs constitutes a normal physiological response that not only enhances repair but also contributes to disease pathogenesis.2 Given its role in both tissue repair and disease progression, pyroptosis has become a key focus in medical research.

Dr. Benjamin Steinberg, an Institute of Medical Science (IMS) alumnus

and faculty member, is a pediatric anesthesiologist and neuroscientist at The Hospital for Sick Children (SickKids).

He studies the molecular mechanisms of cell death to develop new therapeutics and improve patient outcomes for inflammatory diseases such as sepsis and pulmonary arterial hypertension. He completed his MD/PhD at the University of Toronto (U of T) from 2003 to 2011, followed by a residency in Anesthesiology at U of T. In 2013, he pursued additional fellowship training as a resident in Neuroscience and Immunology at the Feinstein Institute for Medical Research in New York under the supervision of Dr. Kevin Tracy. In 2018, he joined SickKids as a staff anesthesiologist and clinician scientist, focusing on the role of cell death in inflammation and disease.

In recent years, Dr. Steinberg’s research has been increasingly focused on pyroptosis, or what he often refers to as “cell rupture.”

He explains, “historically, the field at large assumed that [the] cell rupture component was just a passive process—if a cell cannot sustain [the] energy-requiring process for repair and maintenance, it is effectively metabolically dead and will break apart.” Extending beyond this initial understanding from the field—what has truly fascinated Dr. Steinberg and has guided his research—is understanding the precise terminal events that trigger this lytic cell death process, thereby sparking his interest in this space. In fact, his research group and collaborators

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recently made a groundbreaking discovery, identifying the molecular mechanism by which a membrane protein called Ninjurin-1 (NINJ1) executes the final step of cell rupture.3 The discovery of NINJ1 in cell rupture, as Dr. Steinberg describes, helps “fill the void in our understanding of how the cell death process release[s] all those molecules that we study”, namely DAMPs and proinflammatory cytokines. His research group and others have found that NINJ1 functions through a polymerization event where it forms large protein complexes that cause the cell to break apart or rupture. Still, the question remained: what triggers the polymerization process of NINJ1? Normally, the body is wellequipped to manage cells that undergo programmed cell death by employing pathways like phagocytosis (the removal of dead cells and foreign substances by phagocytes). In contrast, our body is less equipped to handle ruptured cells and the pro-inflammatory damaging molecules they release. This is what makes the study of NINJ1 polymerization of special interest. Dr. Steinberg’s translational objective would be to find a way to hold the cell together, thus preventing the release of pro-inflammatory molecules from ruptured cells.

FEATURE

glycine as a cytoprotective agent better positioned his research group towards more translational projects, aiming to preserve cellular integrity in treating various diseases such as acute liver injury.5 In pre-clinical models, glycine is a valuable tool used to preserve cellular integrity.4 One of the biggest issues with the clinical application of glycine, however, is its poor pharmacokinetics—it may require a very high dosage to achieve the desired effect at a specific target organ. This limitation prompted Dr. Steinberg and his team to explore other potential therapeutic targets.

Dr. Benjamin Steinberg Staff Anesthesiologist, Department of Anesthesia and Pain Medicine at the Hospital for Sick Children (SickKids); Staff Scientist Neuroscience and Mental Health at SickKids; Assistant Professor at the Department of Physiology and Institute of Medical Science Photo Credit: Dr. Steinberg

With the goal of preventing cell rupture and the excessive release of pro-inflammatory molecules, Dr. Steinberg and his team began searching for factors that could regulate NINJ1’s polymerization. Their investigations led them to an intriguing candidate: glycine, one of the simplest amino acids, that appears to play a key role in stabilizing the cell membrane and inhibiting NINJ1induced cell rupture.4 The discovery of Graphic design by Yu-Wen Jan

One avenue of alternative therapeutic targets Dr. Steinberg has investigated is an anti-NINJ1 monoclonal antibody that specifically blocks NINJ1 polymerization, preventing cell rupture. Through collaborations with researchers including Dr. Balyne Sayed—a liver transplant surgeon at SickKids—they demonstrated that anti-NINJ1 antibodies could reduce inflammation associated with liver injury, as demonstrated by a reduction in neutrophil infiltration in their mouse model.5 This breakthrough discovery offers a promising strategy to mitigate

acute inflammatory liver injury in transplantations, particularly those caused by ischemia (impaired blood flow) and subsequent reperfusion (restoration of blood flow to an organ or tissue).

Despite these significant advancements in uncovering new mechanisms of cell death, Dr. Steinberg emphasizes the need to further explore the translational potential of anti-NINJ1 therapies, particularly in treating chronic injuries such as pulmonary vascular disease.

Combining anti-NINJ1 treatments with other interventions may help address the multifaceted nature of chronic diseases.

As Dr. Steinberg notes, “cell death is more nuanced than ever appreciated, and the consequences can be severe.” His research offers a beacon of hope, and a path toward new treatments that could prevent cell-death-related inflammation and ultimately improve the lives of his patients in the future.

References 1. Campisi L, Cummings RJ, Blander Margarian J. Death-Defining Immune Response After Apoptosis. Am J Transplant. 2014 Jun;14(7):1488–1498.

2. Wallach D, Kang TB, Kovalenko A. Concepts of tissue injury and cell death in inflammation: a historical perspective. Nat Rev Immunol. 2014 Jan;14(1):51–9.

3. David L, Borges JP, Hollingsworth LR, et al. NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks. Cell. 2024 Apr 25;187(9):2224-2235.e16.

4. Borges JP, Sætra RS, Volchuk A, et al. Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. eLife. 11:e78609.

5. Kayagaki N, Stowe IB, Alegre K, et al. Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury. Nat. 2023 May;618:1072–1077.

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FEATURE

Neuroinflammation: A Double-Edged Sword?

Delving Deeper into How Neuroinflammation Plays a Role in Multiple Sclerosis and Gliomas

By Hayeon (Nancy) Kim

N

eurodegenerative diseases, like multiple sclerosis (MS) and Alzheimer’s disease, are conditions with a progressive course and currently have no cure.1 Neurodegenerative diseases are characterized by the loss of neurons and the disruption of synaptic connections, leading to cognitive and physical deficits.

In these diseases, neuroinflammation often precedes neurodegeneration.

Neuroinflammation typically serves as a defense mechanism against harmful stimuli—such as injuries and pathogens— within the brain and spinal cord. However, chronic neuroinflammation, a consequence of the failure to resolve the inflammatory stimuli, often leads to neurodegeneration.2 Studying neuroinflammation can aid in early diagnosis and, ultimately, early intervention of neurodegenerative diseases, as expressed by Dr. Amanda Boyle, principal investigator in the Brain Health Imaging Centre at the Centre for Addiction and Mental Health (CAMH). During her PhD in Radiopharmaceutical Sciences at the University of Toronto, she studied preclinical mouse models of gastrointestinal and ovarian cancers using Positron Emission Tomography (PET). Currently, her research focuses on utilizing PET imaging to study neuroinflammation in MS. When asked about the neuroinflammatory mechanisms in MS, Dr. Boyle explained that MS is an autoimmune disease where immune cells found in the bloodstream— T-cells and B-cells—attack the brain and spinal cord. These peripheral immune

cells are typically restricted from entering the brain by the blood-brain barrier.

However, a breakdown of this barrier has been observed in MS, where immune cell infiltration induces glial cell activation towards a pro-inflammatory phenotype.3 In the brain, glial cells—including microglia and astrocytes—maintain brain health by behaving in a pro-inflammatory or anti-inflammatory manner to maintain tissue homeostasis. The chronic activation of glial cells disrupts their homeostatic role of maintaining healthy brain tissue, resulting in inflammatory damage. This chronic neuroinflammation can result in neurodegeneration and progression of MS.3 Neuroinflammation may be quantified

by PET imaging, and could therefore be used as a screening tool for early diagnosis of neurodegenerative diseases.3,4 In one of Dr. Boyle’s current projects, her team is applying PET imaging of neuroinflammation for early diagnosis of MS. They are using a brain-penetrating PET radiotracer that targets a specific membrane-associated protein involved in the neuroinflammatory pathway, known as cyclooxygenase-1 (COX-1). Since this biomarker is primarily located in microglia,5 Dr. Boyle aims to demonstrate that the PET radiotracer will be able to detect changes in microglial behaviour before clinical symptoms emerge in MS. When discussing the preliminary findings from her COX-1 study in MS, Dr. Boyle highlights interesting findings pertaining to sex-based differences. She observed

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that healthy males have lower levels of COX-1 compared to females. However, when clinical symptoms of MS appear, both sexes presented with the same COX-1 levels. This indicates that PET imaging of COX-1 may be more sensitive in the early detection of MS in males compared to females. Future work can aim to investigate additional neuroinflammatory biomarkers beyond COX-1 to better understand what drives the progression of MS symptoms in females. Altogether, these findings may contribute to the development of tailored sex-specific early screening tools for MS. While Dr. Boyle hopes her work can contribute to groundbreaking advancements in the early diagnosis of MS, she also aims to extend her investigation of neuroinflammation to brain cancer research. From an oncology perspective, she noted an extensive overlap between the cell signalling pathways involved in inflammation and cancer. In the brain, there are tumours known as gliomas, which arise from glial cells. As of 2010, roughly 32,260 Canadians have a glioma

FEATURE

radiotracer for early detection of ovarian cancer.7 Based on current preliminary research, Dr. Boyle sees potential in applying this PET-based approach to her current glioma research, further exploring neuroinflammation beyond MS.

Dr. Amanda Boyle PhD Principal Investigator in the Brain Health Imaging Centre at the Centre for Addiction and Mental Health Photo Credit: Nancy Kim

diagnosis, with 5.45 new cases per 100,000 individuals each year.6 These tumours vary in type, and are further classified in terms of their gradings (Grades I-IV), with a higher grade referring to a tumour that is rapidly dividing and more aggressive in nature.6 Dr. Boyle and her team are interested in understanding how healthy glial cells are involved in the formation of tumours. Ultimately, she aims to utilize PET imaging to assist in more accurately diagnosing and staging gliomas. Although the study of neuroinflammation and its role in brain cancer is a relatively new perspective for Dr. Boyle, she has successfully leveraged the crossover between inflammation and cancer by repurposing a COX-1 targeted PET Graphic design by Anaiah Reyes

Another emerging concept in neuroinflammation research is the relationship between neuroinflammation and gut-health. The gut microbiota, which consist of bacteria and fungi in the intestine, interacts with the brain by bidirectional communication along the ‘microbiota-gut-brain axis’. Through this interaction, microbiota can influence neuroinflammation.8 As the understanding of the gut-brain relationship expands, Dr. Boyle prompts us to consider how one’s diet may contribute to the development of neurological disorders. This highlights the wonders of neuroinflammation, demonstrating its involvement not only in neurodegenerative diseases and brain cancers, but also its relation to gut-health.

Dr. Amanda Boyle continues to explore the use of PET imaging for early and enhanced diagnosis of MS and gliomas through examination of biomarkers for neuroinflammation. She believes that machine learning will play a crucial role in PET imaging for neuroinflammation.

She highlights potential limitations of the current status of PET imaging—lengthy scan times, radiation exposure— and hopes that these issues can be addressed by machine learning, by reducing both acquisition time and radiation dose. These

enhancements can be specifically beneficial for children, as the lengthy duration of PET scans and the concerns regarding radiation exposure often precludes the pediatric population from PET scans for disease diagnosis. Ultimately, Dr. Boyle hopes her and her team will continue to play a significant role in these exciting new advancements in PET imaging for the detection of neuroinflammation; one day, allowing for early and enhanced diagnosis and intervention in MS and gliomas.

References 1. Gadhave DG, Sugandhi VV, Jha SK, et al. Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance. Ageing Res Rev. 2024;99:102357. doi:10.1016/j.arr.2024.102357 2. Zhang W, Xiao D, Mao Q, Xia H. Role of neuroinflammation in neurodegeneration development. Signal Transduct Target Ther.

2023;8(1):1-32. doi:10.1038/s41392-023-01486-5 3. Takata F, Nakagawa S, Matsumoto J, Dohgu S. Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction. Front Cell Neurosci. 2021;15. doi:10.3389/fncel.2021.661838 4. Jain P, Chaney AM, Carlson ML, Jackson IM, Rao A, James ML. Neuroinflammation PET Imaging: Current Opinion and Future Directions. J Nucl Med. 2020;61(8):1107-1112. doi:10.2967/ jnumed.119.229443 5. Yang W, Xiong G, Lin B. Cyclooxygenase-1 mediates neuroinflammation and neurotoxicity in a mouse model of retinitis pigmentosa.

J Neuroinflammation. 2020;17(1):306. doi:10.1186/s12974-02001993-0 6. Ji X, Alakel A, Ghazawi FM, et al. Investigation of incidence and geographic distribution of gliomas in Canada from 1992 to 2010: a national population-based study highlighting the importance of exposure to airport operations. Front Oncol. 2023;13:1190366. doi:10.3389/fonc.2023.1190366 7. Boyle AJ, Tong J, Zoghbi SS, Pike VW, Innis RB, Vasdev N. Repurposing 11C-PS13 for PET Imaging of Cyclooxygenase-1 in Ovarian Cancer Xenograft Mouse Models. J Nucl Med Off Publ Soc Nucl Med. 2021;62(5):665-668. doi:10.2967/jnumed.120.249367 8. Bairamian D, Sha S, Rolhion N, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease. Mol Neurodegener. 2022;17(1):19. doi:10.1186/s13024-022-00522-2 9. Mesfin FB, Karsonovich T, Al-Dhahir MA. Gliomas. In: StatPearls.

StatPearls Publishing; 2025. Accessed February 6, 2025. http://www. ncbi.nlm.nih.gov/books/NBK441874/

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 13

FEATURE

Inflammatory Rheumatic Disease Revolutionizing its Diagnosis, Treatment, and Management through Advanced Imaging

By Sreemoyee Ghosh

P

soriatic arthritis (PsA), an inflammatory rheumatic disease (IRD), is a progressive immunemediated inflammatory form of arthritis involving multiple inflammatory musculoskeletal features in the joints, entheses, or the spine. PsA also includes extra-articular features like skin and nail lesions, uveitis, and inflammatory bowel disease. PsA is relatively uncommon in the general population, affecting males and females equally, with a global prevalence of 112 per 100 000 adults.1 PsA pathophysiology is thought to be the result of a complex interplay of genetic, environmental, and immunological factors. Given the clinical heterogeneity of PsA and the non-specific nature of the symptoms, early diagnosis is quite challenging for clinicians, making it an urgent unmet need. Moreover, PsA patients are at an increased risk of developing cardiovascular diseases (CVDs) compared to the general population, which severely impacts lifespan and quality of life.2 Dr. Lihi Eder, a Canadian trailblazer in the field of rheumatology research, is determined to overcome these challenges in PsA research. She is a clinician-scientist at Woman’s College Hospital, where she works as a rheumatologist and is the Director of the PsA research program.

Dr. Eder established this program in 2016 following the completion of her PhD at the Institute of Medical Science and postdoctoral fellowship with Dr. Dafna Gladman at the Krembil Research

Institute. Her PhD research focused on the genetic and clinical epidemiology of PsA, and her postdoctoral studies aimed at understanding the effect of joint inflammation on atherosclerosis development in PsA patients using carotid ultrasound imaging. Through collaboration with Mount Sinai Hospital, Dr. Eder also established the first cardiorheumatology program in Canada, serving as the co-director.

This program at the University of Toronto led by Dr Eder and her colleagues involves 700 patients with rheumatic diseases who were referred to have their cardiovascular risk being evaluated and recruited for cardio-rheumatology research. This number is quite significant, given the rarity of IRDs. She explains that “patients with IRDs tend to be undiagnosed and untreated for high blood pressure, abnormal cholesterol, and diabetes that predispose them to developing heart diseases. Our cardio-rheumatology program is a preventative program that aims to identify IRD patients with a high risk of developing CVDs and treat them early to prevent heart attacks and strokes.”

When asked about some of her group’s most recent research in this domain, she expressed her excitement about the importance of coronary CT scans, stating that, “coronary CT can identify calcification in coronary arteries.

Preliminary results show us that it can be a very useful tool for identifying patients with high risk of heart diseases,

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compared to regular tools like blood tests and physical examinations.” She goes on to further explain the potential of carotid ultrasound in improving the precision of CVD risk stratification in PsA patients, which was demonstrated by one of her prominent studies in collaboration with Toronto Western Hospital in 2019.3 Dr. Eder explains, “PsA patients with severe inflammation in the joints and skin were more likely to develop arrhythmias and heart attacks, suggesting that controlling inflammation might not only be important in treating PsA but also preventing CVDs.”4 With the field of cardio-rheumatology rapidly evolving, she mentions that the future directions of this project are to investigate the effect of antiinflammatory drugs on CVD risk in PsA patients. Therefore, combining ultrasound imaging and anti-inflammatory drugs can effectively diagnose, treat, and manage symptoms in PsA patients with high risk of CVDs. One of the other fundamental questions that Dr. Eder’s research involving ultrasound imaging strives to address is which patients with Psoriasis (PsO)—a chronic immune-mediated inflammatory skin disease—have a high risk of progressing to PsA. Unfortunately, there are no validated biomarkers for identifying PsA in PsO patients. Dr. Eder explains that “early detection of PsA in PsO patients through physical examination of swelling and stiffness in joints is challenging, as in early PsA, inflammation may not be distinct.” To improve screening of

FEATURE

the assessment of multiple joints at the same time.” Thus, ultrasound may be a promising early diagnostic tool for PsA to resolve the issue of diagnostic delays in PsA that cause irreversible joint damage.

Dr. Lihi Eder, MD, PhD Tier 2 Canada Research Chair in Inflammatory Rheumatic Diseases Clinician-scientist and staff rheumatologist at Women’s College Hospital (WCH), Associate Professor of Medicine at the University of Toronto, Director of PsA Program at WCH, Co-Director of UofT Cardio-Rheumatology Program Photo Credit: Dr. Lihi Eder

PsA in PsO patients, and distinguish it from other IRDs, she aims to develop an ultrasound score that will detect the amount of inflammation in joints and tendons. Traditional imaging tools like X-rays identify well-established changes in PsA, such as bone destruction and erosion, but play a limited role in detecting inflammation in early PsA patients.

Emerging to address this issue, there is preliminary evidence suggesting that ultrasound may improve early detection of inflammation in PsA,5 and, Dr. Eder further expresses that, “ultrasound is relatively fast, cheap, safe, and involves Graphic design by Jeah Kim

Additionally, being a Tier 2 Canada Research Chair in IRDs, Dr. Eder and her team have strived to leave no stone unturned in promoting equitable care in PsA: her team has diversified a portion of their research by studying the role that sex and gender play in determining the outcomes for people with PsA. Her research has demonstrated that male patients with PsA are more likely to develop radiographic joint damage than female patients, while females are more likely than men to report limitation in function and impaired quality of life.6 Furthermore, there are sex-specific differences in treatment responses, which may be explained by differences in dysregulation of inflammatory pathways between the two sexes. Dr. Eder emphasizes the importance of this research, in which her lab is now playing a role and building from: one day, the goal is to improve sex-specific treatment recommendations with the design of new clinical trials and the identification of novel inflammatory targets.

Dr. Eder and her colleagues are truly looking forward to revolutionizing diagnosis, treatment, and management of PsA. She is optimistic that the findings from her research program using ultrasound imaging will encourage an

increasing number of rheumatologists to practice implementing ultrasound in the clinic. Dr. Eder underscores the significance of her lab’s research studying cardiovascular comorbidities in PsA patients and the sex-specific effects on PsA outcomes, explaining their importance in providing deeper insights into the immunological and inflammatory mechanisms driving PsA. Looking towards the horizon, she envisions a promising future for IRDs, where clinical and demographic information like imaging results, sex, gender, and age can act as better tools for personalizing treatments and improved care for IRD patients.

References 1. Lembke S, Macfarlane GJ, Jones GT. The worldwide prevalence of psoriatic arthritis-a systematic review and meta-analysis. Rheumatology (Oxford).

2024;63(12):3211-20.

2. Karmacharya P, Ogdie A, Eder L. Psoriatic arthritis and the association with cardiometabolic disease: a narrative review. Ther Adv Musculoskelet Dis. 2021;13:1759720x21998279.

3. Sobchak C, Akhtari S, Harvey P, Gladman D, Chandran V, Cook R, et al. Value of Carotid Ultrasound in Cardiovascular Risk Stratification in Patients With Psoriatic Disease. Arthritis Rheumatol. 2019;71(10):1651-9.

4. Garshick MS, Ward NL, Krueger JG, Berger JS. Cardiovascular Risk in Patients With Psoriasis: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(13):1670-80.

5. Østergaard M, Eder L, Christiansen SN, Kaeley GS. Imaging in the diagnosis and management of peripheral psoriatic arthritis-The clinical utility of magnetic resonance imaging and ultrasonography.

Best Pract Res Clin Rheumatol. 2016;30(4):624-37.

6. Eder L, Thavaneswaran A, Chandran V, Gladman DD. Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis. Ann Rheum Dis. 2013;72(4):578-82.

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 15

FEATURE

The Brain on Lupus: How Dr. Andrea Knight is Shaping Mental Health Research in Rheumatologic Disease

By Priya van Oosterhout

A

ffecting approximately 1 in 1000 Canadians,1 systemic lupus erythematosus (herein referred to as lupus) is a complex, multisystem autoimmune disease. In lupus, the immune system attacks various tissues in the body, resulting in a wide array of symptoms, such as extreme fatigue, seizures, joint pain, and rash.2 It is estimated that 20% of lupus cases worldwide are diagnosed in childhood,3 often translating to a lifetime of ongoing treatment. Furthermore, people with childhood-onset lupus tend to have more brain involvement (referred to as neuropsychiatric lupus) compared to those with adult-onset lupus, with higher rates of depression, anxiety, cognitive difficulties, and even psychosis.4 All of this begs the question: how does childhood-onset lupus affect brain functioning and development?

new exciting drugs coming out, but there was still a lot of psychological burden for the kids and their families.” Dr. Knight asks: is it because of the stress of having a serious chronic illness like lupus? Or is it that children’s brains are more vulnerable to inflammation? Or could it be both?

And how do we improve our treatment for these children?

It remains unclear why patients with childhood-onset lupus have more brain involvement with the disease, and research and treatment hasn’t advanced significantly in this field in the past decades. We know that these symptoms can persist even with aggressive immunotherapy, but until we understand the relationship between lupus and the young brain, the development of specialized therapeutics is not possible.

This is a question being addressed

by Dr. Andrea Knight, a paediatric rheumatologist at the Hospital for Sick Children, and a Canada Research Chair in Mental Health and Chronic Disease of Childhood. Dr. Knight completed her medical education at the Columbia College of Physicians and Surgeons, then went on to pursue her paediatric residency and paediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. While becoming a clinician-scientist was not initially on her radar, she began to notice during her fellowship that many of her rheumatology patients were struggling with mental health. Dr. Knight explains, “We were getting better and better over time at treating the inflammation with 16 | IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY

Now back at the University of Toronto with her own research lab, Dr. Knight is in pursuit of understanding the cognitive deficits associated with childhoodonset lupus. Her team has created a multidisciplinary longitudinal study to paint a comprehensive picture of the adolescent brain with lupus. Employing psychological, pain-related, and cognitive measures, alongside neuroimaging and blood sample analysis, she emphasizes that this study “may end up being one of the largest cohorts in the world with this amount of data for paediatric lupus.”

While the work is still ongoing, her lab’s preliminary findings demonstrate an impact of lupus on the brain both structurally and functionally, even in patients without a clinical diagnosis of neuropsychiatric lupus. With a plan to follow her participants for three years, Dr. Knight and her team are hoping to be able to map trajectories for brain function and development in childhood-onset lupus as her participants reach adulthood.

Beyond characterizing how lupus impacts brain functioning and mental health, Dr. Knight has also begun developing and testing interventions to help her patients with these challenges. The first of these interventions was a remotelydelivered cognitive behavioural therapy program called Treatment and Education Approach for CHildhood-onset lupus (TEACH), developed by psychologist Dr. Cunningham based at Michigan State University. Currently being tested internationally at multiple sites,

FEATURE

that it is, “really exciting to be able to take what we initially characterized and then move towards intervention.” While medication is an important aspect of treating mental health, strategies like therapy and mindfulness—which help individuals learn how to manage their own wellbeing—are also essential.

Dr. Andrea Knight Clinician-Investigator & Associate Scientist at The Hospital for Sick Children Photo Credit: Dr. Knight

including the Hospital for Sick Children in Toronto, TEACH aims to help people with childhood-onset lupus manage their struggles with depression, fatigue, and pain. Additionally, Dr. Knight and her team are also working on a Canadianbased mindfulness intervention for young patients with juvenile arthritis and their caregivers, which has already been met with a lot of enthusiasm by participants.

Though not directly related to lupus, programs like this can be applied across rheumatologic diseases, creating new strategies for mental wellbeing. She adds Graphic design by Lauren Jones

Dr. Knight is not only conducting her own research here in Toronto: she is also shaping how mental health in paediatric rheumatology is being investigated internationally. She is a member of the Childhood Arthritis and Rheumatology Research Alliance (CARRA), a primarily North American network of clinical providers and researchers. Soon after finishing her fellowship, Dr. Knight established CARRA’s Mental Health Working Group, which in many ways, was the first of its kind. Firstly, she conducted a needs-based assessment across CARRA rheumatologists, surveying her colleagues around the globe about the mental health needs and practices in their clinics. She explains how it was, “very eye-opening to see that most of our rheumatology colleagues thought this was important, but admitted that as a whole, they weren’t really doing a great job of integrating this into care.” From these results and a subsequent systematic review of the literature, Dr. Knight and her team were able to create a prioritized research agenda, ranking mental health research topics in terms of importance, feasibility, and actionability in clinical practice. Some of these prioritized topics include mental

health screening, support for patients and families, and identifying the relationship between mental health and chronic inflammatory disease. Creating this prioritized agenda helps ensure that the resources going towards addressing mental health for youth with rheumatologic disease are focused on answering the most critical questions in the field.

When asked about the future of research in the field of childhood-onset lupus, Dr. Knight hopes for a better understanding of the interface between paediatric rheumatologic disease and the impact it has on the brain and mental health.

She emphasizes the importance of a multidisciplinary approach, stating that, “different expertise and specialists have brought my research to another level in terms of really transcending the existing paradigms to move it forward.” Dr. Knight envisions a future with more targeted tools and interventions, so that rheumatologists around the world can treat their patients in all domains of the disease.

References 1. Lupus Canada. What Is Lupus? [Internet]. Newmarket: Lupus Canada; [cited 2025 Feb 15]. Available from: https://www.lupuscanada. org/what-is-lupus/ 2. Lupus Canada. Lupus FAQs: We Asked the Experts [Internet].

Newmarket: Lupus Canada; [cited 2025 Feb 24]. Available from: https://www.lupuscanada.org/lupus-faq/ 3. Levy DM, Peschken CA, Tucker LB, et al. The 1000 Canadian faces of lupus: influence of ethnicity on disease in the pediatric cohort.

Arthritis Care Res. 2013;65(1):152-160. doi: 10.1002/acr.21779 4. Ardoin SP, Daly RP, Merzoug L, et al. Research priorities in childhood-onset lupus: results of a multidisciplinary prioritization exercise. Pediatr Rheumatol Online J. 2019;17(1):32. doi: 10.1186/ s12969-019-0327-4

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 17

FEATURE

Beyond Avoidance: Training the Immune System to Tolerate Food Allergies

By Aria Afsharian

F

ood allergies are a global health problem affecting 1-10% of the world population.1 In Canada, 7.45% of children aged six months to 11 years old are impacted by food allergy, with the most common allergens found in milk, peanuts, and eggs.2 One major allergic pathway involves immunoglobulin E (IgE).3 Normally, food antigens are processed by immune cells and recognized as harmless, releasing signals that suppress IgE production.3 However, in allergic individuals, the immune system mistakes food as pathogenic, increasing pro-inflammatory signals and allergenspecific IgE.3 The most severe form of this response is anaphylaxis, with symptoms like hives and airway constriction.3 Rarely, anaphylaxis can be fatal. The best treatment is prompt epinephrine injection.

Together, these factors necessitate precise predictors of anaphylaxis and a more holistic approach to the diagnosis, prevention, and treatment of food allergies beyond just symptom treatment.

Dr. Julia Upton is a staff immunologist and allergist in the Department of Paediatrics at The Hospital for Sick Children (SickKids). As part of the Division of Immunology and Allergy at SickKids, Dr. Upton’s research is diverse, spanning from oral immunotherapies to predictive immune markers. During our conversation, Dr. Upton explained how approaching the immune system in a simplified manner helps in understanding its role in pathology: “It’s all the immune

system making decisions. What does it fight or not fight? How does it turn on or off its attack?” It is this decision-making process, according to Dr. Upton, that makes the immune system a central target for many diseases and an important area of interest for therapeutic research.

Currently, Dr. Upton is investigating how we can change the immune system’s response to food allergens. “The most obvious way is to eat the food itself,” Dr. Upton says. This thought coincides with studies that show that repeated ingestion of a food allergen can increase the threshold amount that can be tolerated without a reaction. For example, studies have shown that medically managed ingestion of around 300-4000 mg peanut protein can increase the threshold of reaction.5 This strategy is called Oral Immunotherapy (OIT), and it can help train the body to limit reaction in cases of accidental exposures or other instances of micro-exposures.4,5 However, there are challenges to OIT, as a balance is needed between inducing desensitization while minimizing allergic responses.4 Interestingly, exposure to small amounts of food can increase threshold tolerances at magnitudes far greater than the initial dose, as evident in one study where dosages of 500 mg lead to threshold tolerances of 4 g in peanuts in some individuals.4,5 Dr. Upton is exploring even lower OIT doses to try to balance safety and efficacy. She is also studying different routes of administration, such as skin

18 | IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY

patches and under-the-tongue absorption, which can induce desensitization at very low doses.6,7 Aside from dose and routes of entry, the processing of foods also affects their allergenicity due to changes in their chemical structure. For example, how foods change after being cooked can have a substantial effect on allergenicity. Studies have shown that allergic individuals can better tolerate milk and eggs after baking.8,9 Conversely, some foods exhibit greater harm when processed, as seen with peanuts after roasting.8 In addition to external food processing, there are biological factors within the body that can also play a role in allergenicity. Emerging evidence indicates that the bacteria residing in our mouths and intestinal tract may modify the allergenicity of food allergens and reduce anaphylaxis severity.10 Dr. Upton stresses the importance of all these factors in advancing treatment methods, highlighting that, “Understanding how the immune system responds to food after processing helps us minimize the part that triggers the reaction.” This aligns with Dr. Upton’s recent work surveying allergists in North America in their implementation of baked food diets, pushing for more structured guidance on procedures and patient education.9 Current methods of allergy diagnosis are not ideal, relying on giving a suspect food to the patient and tracking reaction progression. This can pose a risk to the

FEATURE

Dr. Julia Upton, MD, MPH Staff Immunologist/Allergist, Department of Paediatrics, The Hospital for Sick Children Photo Credit: Dr. Julia Upton

patient if anaphylaxis ensues post-test. Dr. Upton is interested in improving allergy diagnosis through predictive markers that can be assessed on a patient-to-patient basis. Differences in predictive immune markers can help identify patients at high risk of anaphylaxis, allowing physicians to direct personalized care.

One of these predictive biomarkers, a marker of anaphylaxis, is Platelet Activating Factor (PAF). PAF is a lipidbased compound released by mast cells and macrophages. The factor mediates several pro-inflammatory processes such Graphic design by Emily Huang

as vasodilation.11 PAF is broken down by the enzyme PAF-acetylhydrolase (PAFAH) in the liver.11 Since PAF-AH levels correlate inversely with PAF, it may be possible to use PAF-AH as a marker for anaphylactic severity. To test this, Dr. Upton conducted a trial at SickKids, in which the reaction severity of pediatric patients admitted to the emergency department with acute anaphylaxis was compared to the measured PAF-AH levels in their blood.12 It was found that children with severe anaphylaxis had lower levels of PAF-AH.12 To determine if this pattern was consistent in the absence of an allergic reaction, follow-up tests were performed on the same patients four weeks later, revealing the same result: children who were severely anaphylactic had lower PAF-AH levels even at baseline.12 This was a breakthrough in furthering the understanding of the intrinsic, individual markers that predict one’s vulnerability to allergies.

Our discussions with Dr. Upton converged on a common theme: the need for individualized and personalized care in food allergy treatment discovery. When asked about the future of allergy treatment, Dr. Upton emphasized that a multifaceted, holistic approach is essential: “It is not just about the food or dose, but also these personal and individual factors that we must consider.” By breaking free from the view that strict avoidance is the only way to treat allergies, we can take steps to “teach” our immune system to make the right decisions.

References 1. Gupta R, Marvel J, Tassinari P, T. Mnif, M. Hleyhel, Vincent B, et al.

Global Prevalence of Pediatric and Adult IgE-mediated Food Allergies: Results: FROM THE ASSESS FA STUDY. Annals of Allergy, Asthma & Immunology.2023 Nov 1;131(5): S7–8.

2. Health Canada. Common food allergens-Canada.ca [Internet]. Canada.ca.2019. Available from: https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/food-allergies-intolerances/ food-allergies.html 3. Anvari S, Miller J, Yeh CY, Davis CM. IgE-Mediated Food Allergy.

Clinical Reviews in Allergy & Immunology[Internet].2018 Oct 29;57(2):244–60. Available from: https://pubmed.ncbi.nlm.nih. gov/30370459/ 4. Upton J, Eiwegger T. How Low Should We Go? International Archives of Allergy and Immunology.2015;168(3):147–9.

5. Upton J, Arnon Elizur. Target maintenance dose for peanut OIT is 300 mg protein (or less): Pros and cons. Allergy.2024 Jun 6;79(8):2305–6.

6. Anagnostou A, Upton J, Chinthrajah R. The promise of sublingual and other immunotherapy options for infants and toddlers with food allergy. The Journal of Allergy and Clinical Immunology.

2024Jan1;153(1):95–7.

7. Greenhawt M, Sindher SB, Wang J, O’Sullivan M, George du Toit, Kim EH, et al. Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy. The New England Journal of Medicine.2023May11;388(19):1755–66.

8. Gonzalez PM, Cassin AM, Durban R, Upton J. Effects of Food Processing on Allergenicity. Current Allergy and Asthma Reports.

2025Jan13;25(1).

9. Upton JEM, Lanser BJ, Bird JA, Nowak-Węgrzyn A. Baked Milk and Baked Egg Survey: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee. The Journal of Allergy and Clinical Immunology: In Practice.2023Aug;11(8):2335-2344.e4.

10. Rondeau LE, Sanchez-Martinez E, Garrido-Romero M, Barbosa B, Haas DA, Yuen G, et al. Microbial metabolism of food allergens determines the severity of IgE-mediated anaphylaxis. bioRxiv (Cold Spring Harbor Laboratory).2025Feb19.

11. Upton J, Grunebaum E, Sussman G, Vadas P.Platelet Activating Factor (PAF): A Mediator of Inflammation. BioFactors.

2022Aug27;6(48).

12. Upton J, Hoang JA, Leon‐Ponte M, Finkelstein Y, Du YJ, Khosrow Adeli, et al.Platelet‐activating factor acetylhydrolase is a biomarker of severe anaphylaxis in children. Allergy. 2022Apr9;77(9):2665–76.

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 19

BMC SHOWCASE

Master of Science in

Biomedical Communications

Anatomy of the Kill Canadian Carnivorous Plants Ella Eberhardt Biomedical Communication covers a wide range of topics, and this project encompasses an educational piece on a topic of our choice.

Canadian carnivorous plants hold a special place in my heart and as such I decided to delve in the 4 genus that are native to us and the anatomy behind their kills. Each panel is made to be a tear-away page from the brochure that could alternatively be used as individual posters!

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BMC SHOWCASE

The Happiness In You: The MesolimbicSubcortical Reward Pathway in Humans

Shubhreet Kaur Johal Shubhreet is a second-year MScBMC student and biomedical illustrator-intraining in Toronto, Canada. She is passionate about creating visuals for patient education, medical/research contexts, & post-secondary-level science communication. In her work, she continually aims to prioritize EDIIA representation, and audience needs in knowledge-translation. You can find her work online at esskayjay.carrd.co, or on Instagram @esskay.jay.jpg.

Ink & Instinct: the Biology of the Common Cuttlefish Josip Petrusa Josip is a current graduate student in the Master of Science in Biomedical Communications (MScBMC) program. His interests lie in information visualization, and he hopes to explore the use of interactive tools to communicate scientific information as he continues his graduate studies.

Graphic design by Nichole Zhou

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 21

VIEWPOINT

Mast Cell Activation Syndrome: Immune Response Gone Wrong

As actors in the body’s immune system, mast cells react to the introduction of foreign materials by releasing molecules that cause the inflammatory response we associate with an infection.4 In a healthy immune system, mast cells have several critical functions, not only acting in the body’s defenses against pathogens but also promoting blood vessel growth and tissue repairs. Widespread distribution of these cells ensures that they can react rapidly to an infection.6 Their immune response maximizes its reach by secreting molecules with varied effects on different tissues they encounter. For example, one type of molecule released by mast cells is a cytokine, a small protein involved in immunity. Cytokines can both increase mucous in the respiratory tract and promote movement in the gastrointestinal tract, mobilizing multiple body systems in immunity.4

“

MCAS patients may experience similar responses, possibly even anaphylaxis, without the presence of allergens.

“

Symptoms of MCAS can include hives on the skin, neurological symptoms like memory loss, musculoskeletal pain, and more.

MCAS distorts these necessary functions of mast cells by causing improper activation or hyperactivation.4 Improper mast cell activation plays a role in “traditional” allergies, causing an allergic response when the body is exposed to certain triggers, or allergens.5 MCAS patients, however, may experience similar responses, possibly even anaphylaxis, without the presence of allergens.5 Therefore, MCAS patients may undergo life-threatening anaphylaxis events without clear external cause, in addition to experiencing other symptoms associated with improper mast cell activation.5,7 Because of the distribution of mast cells throughout the body, disorders like MCAS impact multiple body systems, not only worsening patient experiences but also making diagnosis and treatment more difficult.5,7 Symptoms of MCAS can include hives

22 | IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY

“

T

he COVID-19 pandemic has brought with it several health challenges, one of which is an increase in autonomic disease postCOVID-19 infection.1,2 One such disorder is mast cell activation syndrome (MCAS), a condition characterized by the improper activation of immune cells.3 The rise MCAS symptoms after COVID-19 infection suggests that medical professionals should increase awareness of MCAS, promote education on the disease, and familiarize themselves with treatments.3

“

By Grace Gibson

on the skin, neurological symptoms like memory loss, musculoskeletal pain, and more.5 Additionally, MCAS symptoms frequently overlap with those of other conditions, and MCAS is frequently seen in patients with multiple chronic illnesses, most notably Long COVID. These factors contribute to misdiagnoses with other disorders.3,7 The complexity of MCAS requires multiple diagnostic tools and considerations: evaluations of all symptoms in conjunction with each other, blood tests for levels of molecules released by mast cells, and trials with drugs targeting mast cell actions. A patient with ongoing symptoms affecting multiple bodily systems, especially if anaphylaxis is present, may receive an MCAS diagnosis on that basis. However, a positive diagnosis usually requires these symptoms to be found alongside other positive criteria (blood test results and drug test responses).5,7

VIEWPOINT

“

In light of this evidence, medical professionals should familiarize themselves with this condition. MCAS can be difficult to manage, with the triggers for mast cell activation hard to predict and the symptoms varied and potentially severe. For MCAS patients, understanding medical professionals and comprehensive care plans are crucial.

While no cure exists, treatments like antihistamines, mast cell stabilizers, and epinephrine can manage symptoms. A new drug option, omalizumab (Xolair), also appears to effectively decrease anaphylaxis in MCAS patients, offering another new treatment options for severe cases, and ongoing drug trials are examining further options.11 Receiving an accurate diagnosis and effective treatment will help to relieve debilitating symptoms of potentially thousands of people who develop the disease.5 MCAS may seem like a scary diagnosis, but promoting new treatments and increasing awareness can make it much more manageable for patients.

... treatments like antihistamines, mast cell stabilizers, and epinephrine can manage symptoms.

Graphic design by Jeah Kim

References 1. Blitshteyn S, Whitelaw S. Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: a case series of 20 patients. Immunol Res. 2021;69,205–211.

2. Jammoul M, Naddour J, Madi A, et al. Investigating the possible mechanisms of autonomic dysfunction post-COVID-19. Autonomic Neuroscience. 2023;245,103071.

3. Afrin LB, Weinstock LB, Molderings GJ. COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020;100:327-332.

4. Fong M, Crane JS. Histology, Mast Cells [Internet]. Treasure Island (FL): StatPearls Publishing. Available from https://www.ncbi.nlm. nih.gov/books/NBK499904/ 5. Cleveland Clinic. Mast Cell Activation Syndrome [Internet]. [Cited 1 February 2025]. Available from https://my.clevelandclinic.org/ health/diseases/mast-cell-activation-syndrome 6. Church M, Levi-Schaffer F. The human mast cell. JACI. 1997;99(2):155–160.

7. Valent P. Mast cell activation syndromes: definition and classification. Allergy. 15 Feb 2013; 68(4),417–424.

8. Weinstock LB, Brook JB, Walters AS, et al. Mast cell activation symptoms are prevalent in Long-COVID. Int J Infect Dis. 2021 Nov;112:217-226.

9. Munblit D, Bobkova P, Spiridonova E, et al. Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID‐19. Clin Exp Allergy. 2021;51(9),1107–1120.

10. FAIR Health White Paper. A detailed study of patients with longhaul COVID. 15 June 2021.

11. Frieri M. Mast Cell Activation Syndrome. Clinic Rev Allerg Immunol. 2018;54,353–365.

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Because mast cell disorders are not limited to MCAS, an MCAS diagnosis is still rare, and the condition is considered uncommon.5,7 However, ongoing research on the relationship between mast cell activation and COVID-19 suggests that COVID infections may increase MCAS symptoms. Studies of Long COVID (LC) patients, who experience severe symptoms months to years after an initial COVID-19 infection, have shown that mast cell hyperactivation may be responsible for LC symptoms.8 Unfortunately, LC is not a rare condition: surveys of people infected with COVID-19 found that 23.2% of people developed at least one LC symptom after their infection; that number jumped to around 50 percent of those who had been hospitalized with a severe COVID-19 case.8,9,10 These results show that millions of people are at risk of developing LC and accompanying MCAS symptoms as the pandemic continues.

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CBD and Inflammation: A Modern Therapeutic Frontier

By Anna Mouzenian

I

nflammation is a hallmark of numerous chronic diseases, from arthritis to neurodegenerative conditions. As traditional anti-inflammatory treatments often come with significant side effects, the search for safer, natural alternatives has brought cannabidiol (CBD) into the spotlight. Could this naturally derived cannabis compound be the solution we have been seeking? Cannabidiol (CBD) is one of the two main compounds found in the cannabis plant. Unlike tetrahydrocannabinol (THC), CBD is non-psychoactive, meaning it does not produce the “high” commonly associated with cannabis use. According to Harvard Health, CBD can be administered in various forms, including oils, tinctures, capsules, patches, and topical creams, making it versatile for different therapeutic needs. For inflammation, CBD-infused lotions or transdermal patches may offer targeted relief by delivering the compound directly to affected areas.¹

and animal research, indicating CBD’s potential to reduce anxiety, alleviate pain, improve sleep, and reduce cravings for addictive substances.¹ CBD is not entirely without risk but is generally well tolerated, with relatively mild side effects. According to the World Health Organization (WHO), “CBD exhibits no effects indicative of any abuse or dependence potential... there is no evidence of public health-related problems associated with the use of pure CBD.” However, some users have reported side effects such as fatigue, nausea, irritability, and changes in appetite. Additionally, CBD can interact with medications metabolized by liver enzymes—such as blood thinners and immunosuppressants—potentially altering their effectiveness. As a result, consulting a health care provider before use is essential, especially for individuals taking prescription medications.1,3

CBD’s therapeutic potential has been recognized in multiple domains. Most notably, it is approved by the United States Food and Drug Administration (FDA) for treating rare childhood epilepsy syndromes such as Dravet syndrome and Lennox-Gastaut syndrome, where it has been shown to reduce or even eliminate seizures.2 Beyond epilepsy, research suggests CBD’s potential for anxiety, chronic pain, insomnia, and addiction management. While human studies are emerging, much of the existing evidence comes from preclinical 24 | IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY

CBD has demonstrated significant antiinflammatory effects across various preclinical and clinical studies.3,4,5 From a clinical standpoint, its potential for reducing inflammation has been observed in several diseases where inflammation plays a central role. For instance, in Alzheimer’s disease models, CBD has been shown to mitigate neuroinflammation associated with amyloid-beta (Aβ) plaques, a hallmark of the disease, and reduce interleukin-6 levels, suggesting a neuroprotective effect against disease progression.3 Similarly, in rodent models of multiple sclerosis, CBD exerts multi-target anti-inflammatory effects, which may contribute to disease modulation.4 Additionally, preclinical studies in rheumatoid arthritis have demonstrated that CBD not only reduces inflammation, but also provides analgesic effects without impairing daily functioning, reinforcing its therapeutic potential in inflammatory joint diseases.5

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spinal cord), inhibition of Aβ-induced neuroinflammation in cultured astrocytes, and suppression of neutrophil chemotaxis in human neutrophil migration, underscoring CBD’s broad potential in controlling immune-driven inflammation.7

Beyond disease-specific applications, research suggests that CBD’s antiinflammatory effects are largely mediated through its impact on immune signaling.

Studies highlight CBD’s ability to suppress key pro-inflammatory cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), which are critical mediators of the inflammatory response by initiating the inflammatory cascade, amplifying the response and driving the acute-phase reaction, respectively.6 Further preclinical research has identified additional mechanisms, such as reduced immune activation in rodent models of pneumococcal meningitis (bacterial infection of brain and Graphic design by Anaiah Reyes

Despite the promising research on CBD’s anti-inflammatory effects, several limitations must be considered before it can be widely adopted as a reliable treatment. While preclinical studies provide promising evidence for CBD’s anti-inflammatory properties, further human research is necessary. Challenges in conducting studies, for example inconsistencies of doses in animals which can range from 0.5 to 80 mg/kg, have made it difficult to draw definitive conclusions about CBD’s effectiveness in treating inflammatory conditions.6 Additionally, the lack of regulation in the CBD market poses significant challenges. Without standardized formulations, patients may receive inconsistent dosages, potentially leading to variable clinical outcomes and unreliable user experiences.¹ Moreover, global accessibility is further hindered by differing levels of CBD legalisation, which restrict availability and create disparities in its therapeutic use across regions.

CBD holds promise as a potential treatment for inflammation due to its nonpsychoactive nature and relatively mild side effect profile. Preclinical studies have consistently demonstrated its ability to reduce oxidative stress and inflammatory markers, supporting its use as a valuable

therapeutic tool. However, the lack of standardized human trials and concerns over product quality highlight the need for further research and caution in its use.

While more robust clinical data is needed, CBD remains an intriguing alternative for those exploring options beyond traditional anti-inflammatory treatments.

References 1. MD PG. Harvard Health. 2018 [cited 2025 Jan 29]. Cannabidiol (Cbd): What we know and what we don’t. Available from: https:// www.health.harvard.edu/blog/cannabidiol-cbd-what-we-knowand-what-we-dont-2018082414476 2. Abu-Sawwa R, Scutt B, Park Y. Emerging use of epidiolex (Cannabidiol) in epilepsy. J Pediatr Pharmacol Ther [Internet]. 2020 [cited 2025 Feb 3];25(6):485–99. Available from: https://www.ncbi.nlm. nih.gov/pmc/articles/PMC7439947/ 3. Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies.

Cannabis Cannabinoid Res [Internet]. 2017 Jun 1 [cited 2025 Jan 29];2(1):139–54. Available from: https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC5569602/ 4. Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol [Internet]. 2020 Jan [cited 2025 Jan 29];16(1):9–29. Available from: https://www.nature.com/articles/s41582-019-0284-z 5. Lowin T, Tingting R, Zurmahr J, et al. Cannabidiol (Cbd): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis [Internet]. 2020 Sep 1 [cited 2025 Jan 29];11(8):1–11.

Available from: https://www.nature.com/articles/s41419-02002892-1 6. Henshaw FR, Dewsbury LS, Lim CK, et al. The effects of cannabinoids on pro- and anti-inflammatory cytokines: a systematic review of in vivo studies. Cannabis Cannabinoid Res [Internet]. 2021 Jun 10 [cited 2025 Jan 29];6(3):177–95. Available from: https://www. ncbi.nlm.nih.gov/pmc/articles/PMC8266561/ 7. Burstein S. Cannabidiol (Cbd) and its analogs: a review of their effects on inflammation. Bioorganic & Medicinal Chemistry [Internet]. 2015 Apr 1 [cited 2025 Jan 29];23(7):1377–85. Available from: https://www.sciencedirect.com/science/article/pii/ S0968089615000838

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Inflammation: The Aging Brain’s Achilles’ Heel

By Josephine Machado

B

etween the knowledge dissemination we see in the daily news and the lifestyle influencers that flood our social media feed, we’ve all come to understand the impacts that inflammation can have in the latter stages of life. From matcha lattes to incorporating ice-rolling into one’s skincare regime, individuals have sought out a variety of methods to reduce inflammation on a smaller scale. However, in the world of medicine, inflammation has been known to evoke more detrimental effects. The term “inflammaging” has been coined to describe the chronic, sterile, low-grade inflammation that individuals experience as they age.1 Inflamm-aging has been thought to contribute to the pathogenesis of a variety of age-related diseases throughout the body as we advance into adulthood.1 It’s important to be aware of the variety of ways in which age-related inflammation can affect our health as a result of its systemic nature. Conditions such as osteoarthritis and inflammation-related joint concerns are known issues in the aging population, but inflamm-aging transcends this. Scientists have come to dedicate significant time to evaluating the impact of inflammation on the aging of the brain. We’ve all heard of dementia or Alzheimer’s disease, but what is the role of inflammation in the development of these conditions?

Inflamm-aging & The Brain Brain-aging refers to a decline in the structure and, consequentially, the function of the brain with age. This includes decreased nerve cells, a loss of neural network connections, cognitive decline, mood swings, and behavioural changes.2 In terms of impact on functionality, the effects of brain-aging are vast. Brain-aging can significantly contribute to the decline of a variety of cognitive functions. This includes speed of information processing, as well as plasticity—which refers to the brain’s ability to adapt and create new connections between neurons in response to learning or injury. Brain-aging can also affect one’s capacity of working memory and spatial memory, which refer to the brain’s ability to temporarily hold and process information for tasks, and remember the arrangements of objects in one’s environments respectively.3 The brain-age gap can be defined as the difference between a person’s estimated biological brain-age and their chronological age (better known as their “actual” age). Current advances have used machine learning models to calculate this gap using MRI scans.4 Recent research has named neuroinflammation as the primary cause of brain-aging. The aging of brain cells leads to the upregulation of

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inflammatory pathways, causing issues with brain-function and increased inflammation damage.3 When too intense, immune responses can damage surrounding tissues and cause autoimmune pathologies, especially within the brain where neuronal regeneration is poor.5 Additionally, as individuals age, their microglia—the resident immune cells of the brain—lose the ability to clear misfolded proteins, which are linked to neurodegeneration. This dysfunctional protein clearance significantly contributes to the neuroinflammatory response observed in the brain.3 Brain-aging and neuroinflammation exist as a feedback loop, where aging processes such as protein misfolding cause inflammation, and inflammation can in turn accelerate brain-aging.

As mentioned, brain-aging has been linked to neurodegeneration; a serious issue in the realm of geriatric health. Neuroinflammation is significantly enhanced by the accumulation of amyloid beta plaques, which are clumps of neurotoxic proteins that disrupt signals, damage brain cells, and accelerate the progression of Alzheimer’s disease through several pathways. Additionally, chronic inflammation is associated with a wide array of neurodegenerative diseases of aging.

This isn’t limited to Alzheimer’s disease— Parkinson’s disease and amyotrophic lateral sclerosis are included as well.6

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Brain-aging in Action: The Study of Brainaging in Autoimmune & Inflammatory Conditions The computation of one’s brain-age gap has been an up-and-coming measure in the fields of neuroscience and behaviour.

The link between brain-aging and neuroinflammation is a topic of concern for not only elderly populations, but individuals with inflammatory conditions as well. Thus, brain-aging has become an emerging topic of interest in rheumatology and autoimmune disorders across both pediatric and adult populations.

Brain-age has been computed in several studies evaluating patients with multiple sclerosis (MS), a chronic, inflammatory, autoimmune disease which damages the central nervous system.7 This inflammation is caused by an abnormal immune response that attacks myelin—a fatty, protein-rich material that coats neurons, which acts to insulate them and speed up electrical impulses.8 A recent multi-center study used a machine learning model to compute biological brain-age in 195 patients with relapsing remitting MS. The results revealed accelerated brain-aging and a larger brainage gap in patients with MS, with a mean of +6.98 years, in comparison to healthy subjects, with a mean brain-age gap of +0.23 years. The study concluded that the

Graphic design by Yu-Wen Jan

brain-age gap is a viable surrogate marker of disease progression in MS patients.9 Similarly, another study used a machine learning model to predict biological age in 70 females with systemic lupus erythematosus (SLE), an autoimmune condition in which the body’s immune system attacks its own tissues, leading to systemic inflammation and possible multi-organ damage. The study found that individuals with SLE had brains that appeared 3.6 years older than healthy controls. They also found that SLE individuals with a high brain-age exhibited neuropsychological deficits including significantly longer reaction times, and decreased psychomotor speed and flexibility.10 Overall, the study of autoimmune disorders— where inflammation is an inherent issue—can continue to provide insights into the impacts of neuroinflammation on brainaging and cognition.

Age-related inflammation has historically held significant meaning in a variety of medical specialties, however, the link between neuroinflammation and brainaging is a novel field that has shown great promise for both clinical and researchbased purposes. Continuing to invest time and resources in deepening our knowledge on this connection can lead to significant advances in our understanding

of the neurological effects of autoimmune conditions, as well as normal inflamm-aging. Understanding these processes is the first step in mitigating neuroinflammation and developing interventions that can act to prevent or even reduce its negative effects.

References 1. Franceschi C, Garagnani P, Parini P, et al. Inflammaging: a new immune–metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14(10):576–90. https://doi.org/10.1038/s41574018-0059-4 2. Aging Biomarker Consortium, Jia YJ, Wang J, et al. A framework of biomarkers for brain aging: a consensus statement by the Aging Biomarker Consortium. Life Medicine. 2023;2(3):lnad017. https:// doi.org/10.1093/lifemedi/lnad017.

3. Li X, Li C, Zhang W, et al. Inflammation and aging: signaling pathways and intervention therapies. Sig Transduct Target Ther.

2023;8(1);239. https://doi.org/10.1038/s41392-023-01502-8.

4. Soumya Kumari LK, Sundarrajan R. A review on brain age prediction models. Brain Research. 2024;1823:148668. https://doi. org/10.1016/j.brainres.2023.148668.

5. Kip E, Parr-Brownlie LC. Healthy lifestyles and wellbeing reduce neuroinflammation and prevent neurodegenerative and psychiatric disorders. Front Neurosci. 2023;17:1092537 https://doi. org/10.3389/fnins.2023.1092537.

6. Balestri W, Sharma R, Da Silva VA, et al. Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases. J Neuroinflam1mation. 2024;21(1):32. https://doi.org/10.1186/ s12974-024-03024-8.

7. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. CellJ. 2017;19(1);1-10. https://doi.org/10.22074/cellj.2016.4867.

8. Morell P, Quarles RH. The Myelin Sheath: molecular, cellular and medical aspects. In: Siegal GJ, Agranoff BW, Agranoff RW, Fisher SK, Uhler MD, editors. Basic neurochemistry: molecular, cellular and medical aspects. 6th ed. Philadelphia: Lippincott-Raven Publishers; 1999.

9. Romme CJA, Stanley EAM, Mouches P, et al. Analysis and visualization of the effect of multiple sclerosis on biological brain age. Front Neurol. 2024;15:1423485. https://doi.org/10.3389/ fneur.2024.1423485.

10. Kuchcinski G, Rumetshofer T, Zervides KA, et al. MRI BrainAGE demonstrates increased brain aging in systemic lupus erythematosus patients. Front Aging Neurosci. 2023;15:1274061. https://doi. org/10.3389/fnagi.2023.1274061.

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The Climate is Changing —and so are your

Allergies

By Abigail Wolfensohn

I

t is a pleasant spring day. While many are eager to finally enjoy the great outdoors without the burden of heavy parkas and winter boots, if you’re one of the estimated 20-25% of Canadians with seasonal allergies,1 you may be bracing yourself for weeks of pollen-induced itchiness and congestion instead. You may even be yearning for the days when your seasonal allergies didn’t seem this bad. If this sounds like you, it isn’t your imagination—this trend of progressively worsening allergies is a growing public health concern that is not limited to seasonal allergies alone. Allergies are becoming more prevalent and severe every year, and human-driven climate change is a likely culprit.

components: pollen concentrations in the air, the duration of pollen exposure, and the allergenicity of said pollen.3 Climate change amplifies each of these factors, intensifying seasonal allergies.

One way climate change exacerbates seasonal allergies is by driving the spread of allergenic plants into regions where they were not previously found, exposing millions of new people to allergyinducing pollen. For example, ragweed, a plant native to the Americas, produces pollen that commonly causes allergies in late summer and fall. Due to shifts in climate, ragweed’s range is rapidly expanding poleward as temperatures rise and more areas become suitable habitats,

How could climate change be contributing to this phenomenon? As humans burn fossil fuels, greenhouse gases trap heat in the atmosphere, causing global temperatures to rise. This leads to extreme weather patterns and ecological shifts, which are further exacerbated by human activity, such as deforestation and other forms of environmental destruction.

Despite overwhelming scientific evidence, global responses to climate change have been inadequate, with insufficient action being taken to curb carbon emissions and mitigate the escalating impacts on ecosystems and human health.2 When it comes to seasonal allergies, these environmental changes significantly impact the growth patterns of allergenic plants. The development and severity of a pollen allergy depend on three key 28 | IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY

transforming it into a globally invasive species.4 Deforestation and urban development have also contributed to its spread, since ragweed thrives in disturbed soil.5 A landmark 2017 study projected that the rate of sensitization—a necessary step in the development of an allergy—to ragweed will more than double in Europe by the mid-21st century due to climate change.5 In addition to expanding the range of allergenic plants, climate change is also extending allergy seasons by lengthening the growing seasons of allergenic plants.

When allergenic plants thrive for a longer period without succumbing to frost damage, allergy seasons begin earlier in

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the spring and end later in the fall. A 2021 study analyzing long-term pollen records from 60 North American cities between 1990 and 2018 found that by 2018, springtime pollen seasons were starting 20 days earlier and lasting eight days longer on average compared to 1990.

Using climate modeling, the authors estimated that human-caused climate change alone was responsible for around 50 percent of this shift.6 Moreover, mounting evidence suggests that rising temperatures and air pollution affect the quantity and allergic potency of airborne pollen. In fact, springtime pollen concentrations in North America are on average 21.5% higher than they were three decades ago.6 Indeed, at higher temperatures, plants tend to grow more vigorously and produce greater amounts of pollen with higher allergen concentrations. This effect has been observed in numerous studies on ragweed, birch, cypress, grass, and other plants that commonly cause seasonal allergies.3,7 The impact of climate change on allergies extends beyond seasonal allergies. Rising temperatures, higher CO2 levels, and extreme weather, such as heavy rainfall, increase the abundance and potency of mold and poison ivy.3,8 Allergy rates to house dust mites, a common indoor allergen that thrives in warm, humid conditions, have also significantly increased worldwide.9 Graphic design by Lauren Jones

Beyond influencing many allergens responsible for allergic diseases, climate change has increased human exposure to ambient air pollution, which could further aggravate the allergic response.

Inhaling pollutants could impact the immune system’s response to potential allergens and make us more prone to developing allergies.2 This may even extend to food allergies. A longitudinal study conducted in Australia, published in December of 2024, demonstrated a significant association between elevated exposure to air pollution during infancy and persistent peanut allergy throughout the first ten years of life.10 Other consequences of climate change, such as loss of biodiversity, water pollution, and increased prevalence of wildfires and dust storms,2 may also increase the prevalence and severity of allergies, as these events can alter human microbiome composition and immune function.

The consequences of climate change exacerbating allergies are a pressing public health concern, given the wide-reaching societal and individual burden these changes impose. Addressing this issue will require a coordinated global effort.

On a systemic level, this means reducing greenhouse gas emissions, preventing environmental degradation, substantially investing in environmental and health science research, and implementing strategies to protect vulnerable populations. On an individual level, we can contribute by advocating for policy changes, educating those around us,

and staying informed about local pollen and air quality conditions. Ultimately, the fight against allergies is part of a broader challenge—protecting human health in an increasingly unpredictable environmental landscape.

References 1. Keith PK, Desrosiers M, Laister T, et al. The burden of allergic rhinitis (AR) in Canada: perspectives of physicians and patients. Allergy Asthma Clin Immunol. 2012 Jun 1;8(1):7.

2. Seastedt H, Nadeau K. Factors by which global warming worsens allergic disease. Annals of Allergy, Asthma & Immunology. 2023 Dec 1;131(6):694–702.

3. Ziska LH, Epstein PR, Schlesinger WH. Rising CO2, Climate Change, and Public Health: Exploring the Links to Plant Biology.

Environ Health Perspect. 2009 Feb;117(2):155–8.

4. Oswalt ML, Marshall GD. Ragweed as an Example of Worldwide Allergen Expansion. Allergy Asthma Clin Immunol. 2008 Sep 15;4(3):130–5.

5. Lake IR, Jones NR, Agnew M, et al. Climate Change and Future Pollen Allergy in Europe. Environ Health Perspect. 2017 Mar;125(3):385–91.

6. Anderegg WRL, Abatzoglou JT, Anderegg LDL, et al. Anthropogenic climate change is worsening North American pollen seasons.

Proceedings of the National Academy of Sciences. 2021 Feb 16;118(7):e2013284118.

7. Sénéchal H, Visez N, Charpin D, et al. A Review of the Effects of Major Atmospheric Pollutants on Pollen Grains, Pollen Content, and Allergenicity. ScientificWorldJournal. 2015;2015:940243.

8. Paudel B, Chu T, Chen M, et al. Increased duration of pollen and mold exposure are linked to climate change. Sci Rep. 2021 Jun 17;11(1):12816.

9. Acevedo N, Zakzuk J, Caraballo L. House Dust Mite Allergy Under Changing Environments. Allergy, Asthma & Immunology Research.

2019 May 14;11(4):450.

10. Lopez DJ, Lodge CJ, Bui DS, et al. Air pollution is associated with persistent peanut allergy in the first 10 years. Journal of Allergy and Clinical Immunology. 2024 Dec 1;154(6):1489-1499.e9.

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How Your Diet Can Heal or Harm The Science Behind Anti-Inflammatory Eating

By Emily Wiljer

W

ould you give up ice cream again if doing so could prevent cancer, cardiovascular disease, or Alzheimer’s? This is a question you might consider before starting an antiinflammatory diet.

Inflammation is a natural and essential process that acts as the first line of defense against injury and disease. However, not all inflammation is created equal.

Beneficial inflammation—known as acute inflammation—is recognizable in the redness and pain you might experience after getting a cut and promotes healing.

However, chronic inflammation can be caused by lifestyle choices, persisting for months, or even years. This has been linked to a variety of health issues, including cardiovascular disease, diabetes, autoimmune disorders, and neurodegenerative conditions.1

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Diet plays a central role in exacerbating or mitigating inflammation.

Diet plays a central role in exacerbating or mitigating inflammation. Foods high in sugars, trans fats, and refined carbohydrates raise levels of biomarkers like C-reactive protein (CRP) and pro-inflammatory cytokines.1 In contrast, a diet emphasizing omega-3 fatty acids and antioxidants can lower these markers and promote a healthier inflammatory response. Oxidative stress, caused by an imbalance between free radicals and antioxidants, also drives chronic inflammation. Unhealthy diets exacerbate this imbalance, leading to cellular damage, whereas incorporating antioxidant-rich foods into your diet helps to counteract oxidative stress and reduce chronic inflammation.2 Which foods are particularly rich in anti-inflammatory nutrients? Fatty fish, such as salmon, mackerel, and sardines, are rich in omega-3 fatty acids and help decrease CRP and pro-inflammatory cytokine levels.1 Leafy greens, berries, nuts, and seeds are rich in antioxidants and polyphenols, which have been shown to combat oxidative stress.3,4 Whole grains and legumes are high in fibre, which helps to regulate inflammation by improving gut health.5 Foods containing monounsaturated fats, such as olive oil and avocados, are staples, due to their suggested direct and indirect roles in modulating immune responses.6 It can also be beneficial to add turmeric into your foods and drinks, as turmeric contains curcumin, a powerful anti-inflammatory compound.7 For caffeine lovers, green

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tea and coffee contain polyphenols, which have antioxidants and antiinflammatory properties.8 Anti-inflammatory diets also call for reducing the intake of trans fats, refined sugars, red and processed meats, and excessive alcohol. Trans fats cause an increase in ‘bad’ cholesterol (low-density lipoprotein, LDL) levels while also reducing ‘good’ (high-density lipoprotein, HDL) cholesterol levels, which can lead to inflammatory diseases, such as stroke and heart disease.9 Consuming refined sugars spike blood sugar levels and increase inflammatory markers.10 Red meats and processed meats are also associated with higher CRP levels and should be avoided.11 Say goodbye to that Happy Meal with fries!

Furthermore, consuming excess amounts of alcohol and sugary sodas can trigger oxidative stress and systemic inflammation.2 Anti-inflammatory diet principles have also been incorporated into clinical practice. The MIND diet, or Mediterranean-DASH Intervention for Neurodegenerative Delay diet, was developed with the focus on promoting foods that reduce brain inflammation and improve cognitive health. Key components of the diet include the regular consumption of fish and poultry, using olive oil as a primary fat source, and lowering alcohol intake. The diet also encourages the consumption of leafy greens, berries, nuts, and whole grains, which encompasses all the key principles of an anti-inflammatory diet. Research

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Overall, the principles of an antiinflammatory diet serve as the best practice for fostering a balanced, health-focused relationship with food. Prioritize eating a variety of whole, unprocessed foods, and remember that balance is key. By making gradual changes, listening to your body, and seeking professional advice, you can take meaningful steps toward reducing inflammation and cultivating a healthier life.

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Anti-inflammatory diets are a powerful, holistic approach to improving overall health and reducing the risk of chronic diseases.

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References

has shown that adherence to the MIND diet significantly reduces the risk of Alzheimer’s disease and cognitive decline.11 These studies demonstrate the potential of diets in modifying risk for developing neurodegenerative diseases.

grains. Worried about not being creative enough to create appropriate recipes? Ask ChatGPT (or your favourite AI tool) to create an anti-inflammatory meal plan that matches your budget and embodies MIND core principles and tricks.

Despite these benefits, some people may worry about the practicality of adopting an anti-inflammatory diet. In reality, there are plenty of tips to incorporate into your daily eating. Meal-planning and ingredient shopping at the beginning of the work week allows you time to prepare recipes that follow anti-inflammatory principles.

Incorporate MIND principles by adding berries and leafy greens to smoothies or salads and swapping unhealthy fats for olive oil. When dining out, choose a baked or grilled option over fried foods. Students or those who are budget-conscious can opt for frozen vegetables and bulk

Anti-inflammatory diets are a powerful, holistic approach to improving overall health and reducing the risk of chronic diseases. However, it is important to remember that individual results may vary. What works well for one person might need adjustments for another, depending on unique health conditions, dietary preferences, or lifestyle factors.

This is why consulting a healthcare provider or registered dietitian before making significant dietary changes is essential. Their guidance can help tailor an anti-inflammatory approach that best meets your specific needs.

Graphic design by Emily Huang

1. Calder, PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? British Journal of Clinical Pharmacology. Ar. 2011;75(3):645-62. doi: 10.1111/j.13652125.2012.04374.x.

2. Tan BL, Norhaizan ME, Liew WP, Sulaiman Rahman H. Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases. Front Pharmacol. 2018 Oct 16;9:1162. doi: 10.3389/ fphar.2018.01162.

3. Aune D, Giovannucci E, Boffetta P, Fadnes LT, Keum N, Norat T, Greenwood DC, Riboli E, Vatten LJ, Tonstad S. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and allcause mortality-a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol. 2017 Jun 1;46(3):10291056. doi: 10.1093/ije/dyw319.

4. Ros E. Health benefits of nut consumption. Nutrients. 2010 Jul;2(7):652-682. doi: 10.3390/nu2070652..

5. Al Bander Z, Nitert MD, Mousa A, Naderpoor N. The Gut Microbiota and Inflammation: An Overview. Int J Environ Res Public Health. 2020 Oct 19;17(20):7618. doi: 10.3390/ijerph17207618.

6. Benjamin B. How fats we eat modulate our immunity? OCL, 27 (2020) 22. DOI: https://doi.org/10.1051/ocl/2020009 7. Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017 Oct 22;6(10):92. doi: 10.3390/ foods6100092.

8. Chatterjee A, Saluja M, Agarwal G, Alam M. Green tea: A boon for periodontal and general health. J Indian Soc Periodontol. 2012 Apr;16(2):161-7. doi: 10.4103/0972-124X.99256..

9. Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Trans fatty acids and cardiovascular disease. N Engl J Med. 2006 Apr 13;354(15):1601–13. doi: 10.1056/NEJMra054035.

10. Ma X, Nan F, Liang H, Shu P, Fan X, Song X, Hou Y, Zhang D. Excessive intake of sugar: An accomplice of inflammation. Front Immunol. 2022 Aug 31;13:988481. doi: 10.3389/fimmu.2022.988481.

11. Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015 Sep;11(9):1007-14. doi: 10.1016/j.jalz.2014.11.009

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Microdosing Allergies The Key Risks and Benefits of Oral Immunotherapy for Food Allergies

F

rom grabbing a snack with co-workers to enjoying dinner with friends, food is often the centrepiece of our day-to-day social interactions. As such, severe food allergies (FA) can often be a lifelong sentence of fastidious label-checking, careful food preparation, and restricted social opportunities. With self-reported FA increasing in prevalence across Canada1, the need for new treatment approaches is imperative. But what if a cure to debilitating allergies lies in leveraging the allergen itself? Oral immunotherapy (OIT)—the practice of ingesting micro-doses of allergens—has gained traction as a treatment for FA1 and may offer an approach to achieving food freedom by desensitizing food allergens and reducing allergic reactions.

To understand how OIT works, it is important to first understand what causes FA. FA is distinct from food sensitivities or intolerances as it causes an immunologic event, in which the body mistakenly responds to proteins in food as pathogens.2 For example, in peanut allergies, peanut proteins (e.g., AraH1 or AraH2) are identified as a threat by immunoglobulin E cells (IgE).

Typically, IgE antibodies mark invading pathogens, which mediate a largescale immune reaction by activating inflammatory cells such as macrophages and mast cells, leading to the onset of allergic symptoms. In OIT, the idea is to desensitize this response over time through repeated small exposures to the

“

FA is distinct from food sensitivities or intolerances as it causes an immunologic event, in which the body mistakenly responds to proteins in food as pathogens

allergen. While the precise mechanisms by which OIT alleviates allergies remains under investigation, several lines of research corroborate a reduced immunologic response following OIT, characterized by reduced mast cell and basophil reactivity and increased activity of T-regulatory cells, which suppress the general immune response.3 OIT typically involves a regimen of dosing food allergens mixed with a safe “vehicle” food (e.g., applesauce or yogurt).4 Allergen doses increase incrementally over time to build tolerance and desensitize individuals to the food allergen.

In recent years, OIT has seen a rise in public awareness, in part due to its coverage on social media. TikTok and Instagram users use the hashtag #oralimmunotherapy to document their journeys with OIT treatment. However, underlying these trends are decades of allergy and immunology research.

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“

By Jasmine Amini

A 2022 meta-analysis of 39 randomizedcontrolled trials (RCT) (n = 2126 participants, mainly children) found that oral immunotherapy was effective in increasing tolerance to peanuts, cow’s milk, and hen’s egg.5 While longitudinal OIT clinical trials are scarcer, the literature is slowly growing. In a twoyear follow-up study of a probiotic and peanut OIT trial, >70% of participants achieved at least desensitization (i.e., heightened threshold for allergic reaction) to allergic reactions over time across all treatment groups.6 In addition to clinical trial outcomes of lower immunological reactivity posttreatment, OIT has the potential to drastically and positively impact the quality of life of those afflicted with food allergies. One prospective cohort study (n= 175 participants) from 2019 demonstrated that children undergoing OIT had scores on the Food Allergy Quality of Life Questionnaire significantly improved from OIT initiation to full maintenance (i.e. up to 3 years). Quality of life scores were particularly improved on subscale items relating to food anxiety, social and dietary restrictions, and emotional impact.7

VIEWPOINT

While anecdotal, the active OIT-based social media community also frequently echoes these benefits, crediting OIT with reducing the chronic burden of living with severe allergies, for both patients and their families. For one TikTok user, @AllergicGina, OIT has provided a sense of security for her niece Evelyn, who suffers from a severe peanut allergy, stating, “[Oral] Immunotherapy has removed that constant gripping fear of ‘if I have something that’s crosscontaminated, I will die’…”. 8 However, OIT does not come without its criticisms or failures. Foremost, in some cases, OIT has been shown to increase allergic and anaphylactic reactions.9 For example, a meta-analysis from 2019 that included 12 OIT trials (n = 1041 participants) for peanut allergy found OIT increased anaphylaxis risk and frequency of anaphylactic reactions during both the treatment and maintenance periods.10 Notably, these anaphylactic reactions occurred despite Graphic design by Jeah Kim

achieving immune desensitization, meaning that participants had previously tolerated similar doses of the allergen while supervised in-clinic. Other criticisms of OIT include poor clinical trial standardization and reporting: to date, there is little consensus on which outcomes should be reported, and few studies examine allergic responses longitudinally.9 Moreover, OIT is only a viable treatment option for a select population, and, as such, cannot be viewed as a “catch-all” therapy. Current evidence corroborates the use of OIT to treat peanut, cow’s milk, and hen’s egg allergies5,9, but current studies show seldom focus on other common allergens such as soy, tree nuts, or shellfish. Finally, OIT is primarily safe and effective for infants and children with FA. One study comparing OIT effectiveness among children, adolescents, and adults found that adults were more likely to experience adverse reactions and achieve lower levels of allergen desensitization, reducing the potential clinical impact of OIT for the adult population.11 OIT offers an exciting, novel approach to the longstanding challenge of food allergies. However, further research is vital to overcoming current efficacy limitations. Identification of reliable biomarkers and treatment outcomes for OIT are critical first steps in establishing solid evidence for OIT efficacy or inefficacy. Further standardization of OIT protocols within RCTs is also

necessary to compare results between trials. Finally, cautious expansion of OIT treatment into other priority allergens, like soy, and across age groups is crucial to advancing allergy treatment and supporting the greatest number of individuals. With an ever-expanding literature base, OIT has the potential to revolutionize allergy treatment, one microgram of peanut protein at a time.

References 1. Clarke AE, Elliott SJ, St Pierre Y, et al. Temporal trends in prevalence of food allergy in Canada. J Allergy Clin Immunol Pract 2020; 8: 1428-1430.e5.

2. Lopez CM, Yarrarapu SNS, Mendez MD. Food Allergies.

In: StatPearls. Treasure Island (FL): StatPearls Publishing, http://www.ncbi.nlm.nih.gov/books/NBK482187/ (2025, accessed 21 January 2025).

3. Gorelik M, Narisety SD, Guerrerio AL, et al. Immunologic Suppression To Peanut During Immunotherapy Is Often Transient. J Allergy Clin Immunol 2015; 135: 1283–1292.

4. Wood RA. Oral Immunotherapy for Food Allergy. J Investig Allergol Clin Immunol 2017; 27: 151–159.

5. de Silva D, Rodríguez del Río P, de Jong NW, et al. Allergen immunotherapy and/or biologicals for IgE-mediated food allergy: A systematic review and meta-analysis.

Allergy 2022; 77: 1852–1862.

6. Loke P, Wang X, Lloyd M, et al. Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 LongTerm (PPOIT-003LT) study. Allergy 2024; 79: 2759–2774.

7. Epstein-Rigbi N, Goldberg MR, Levy MB, et al. Quality of Life of Food-Allergic Patients Before, During, and After Oral Immunotherapy. J Allergy Clin Immunol Pract 2019; 7: 429-436.e2.

8. AllergicGina on TikTok. TikTok, https://www.tiktok. com/@allergicgina/video/7299125208730848517?_ t=ZM-8tOlnpVb1K1&_r=1 (accessed 26 January 2025).

9. Mori F, Giovannini M, Barni S, et al. Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate. Front Immunol 2021; 12: 636612.

10. Chu DK, Wood RA, French S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. The Lancet 2019; 393: 2222–2232.

11. Epstein-Rigbi N, Levy MB, Nachshon L, et al. Efficacy and safety of food allergy oral immunotherapy in adults.

Allergy 2023; 78: 803–811.

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 33

STUDENT SPOTLIGHT

Making Every Moment Count: How Stefan Aguiar finds Meaning through Connection

By Katherine Guo

I

f you’re a student at the Institute of Medical Science (IMS), you’ve probably heard of Stefan Aguiar. From leading two separate student organizations to patient recruitment and research, Stefan does it all.

As a PhD student at IMS, most of Stefan’s thesis work takes place at Princess Margaret Hospital (PMH), where he is supervised by Dr. Madeline Li. Stefan focuses on psychosocial oncology as well as palliative and end-of-life care for patients who have requested medical assistance in dying (MAiD). When discussing his initial interest in the field, his family is always at the forefront of the conversation.

He initially describes how his parents immigrated from India to help with his chronic asthmatic conditions and to escape the poor air quality and pollution in his hometown. So, when Stefan began his undergraduate degree at the University of Toronto in 2018, he set his sights on majors related to immunology where he could learn more about allergies, asthma and cancer. His choice of joining Trinity College, which has a strong focus on immunology, cemented his interest. With his mind made up, he specialized in the Immunology and Health and Disease streams in 2020.

Although becoming a physician was on the table, Stefan was also interested in pursuing a career in research. Cuttingedge microbiome research was a hot

topic in the world of gut immunology, so when presented with the chance to work with gut immunology researchers Dr. Dana Philpott and Dr. Thierry Mallevaey midway through his undergraduate degree, Stefan jumped at the opportunity.

His project focused on the NOD2 receptor and its role in innate immune system activation via gut bacteria. Stefan’s role was to work on a cellular model to test for receptor activation.

Stefan enjoyed his research work so much that he joined the Immunology Summer Student Research Program and continued with the lab to complete his 4th-year thesis. Soon, he began looking into graduate school, knowing the process was another chance to refine his research focus. When he talks about deciding the kinds of supervisors to apply to, he again goes back to his family.

He describes how his grandfather “suffered for a very long time” from cancer as well as the discrepancy between his experience and his studies.

His undergraduate degree had been somewhat detached and depersonalized; it was all mechanisms, cell biology, and treatments. But after witnessing, firsthand, what it was like for patients in an oncology unit, Stefan was interested in something more holistic.

“What about the human aspect of it?

People actually suffering with cancer—are we taking care of them?”

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While searching for a supervisor, Stefan came across Dr. Li, whose work was primarily focused on both immunology and cancer within the context of endof-life care. Although it was a big switch from benchwork, it was a perfect match— allowing him to explore both of his research interests in a dry-lab environment.

Now, Stefan interviews patients in PMH’s oncology unit who have requested MAiD, combining both qualitative and quantitative data with the goal of teasing out the nuances related to their experiences and patient profiles. Recruited patients also complete psychometric questionnaires every six months to assess the various psychosocial factors impacting their wellbeing. Stefan recalls the beginning of his work as particularly challenging since “there’s no formal training before you talk to patients who are about to die.”

Recruited patients are in the later stages of cancer, often with a life expectancy of 2 years at maximum. While some patients are interviewed far in advance of their MAiD date, other interviews take place only a week before. It goes without saying that the work is emotionally demanding.

Despite the emotional toll, Stefan reflects on his work and the people he’s met with reverence—grateful to have been allowed into their lives, however brief. “These patients are at the last stages of their life,” he says. “I see it as having the privilege to go and spend that time with them.”

STUDENT SPOTLIGHT

PMH site director that year, also convinced Stefan to get involved with IMS Student Association (IMSSA). She passed on the torch to Stefan where he succeeded her as site director in his second year. There, Stefan also became involved with IMSSA’s Warm Hands for Cold Streets event and party planning committee in addition to his role as site director.

Stefan Aguiar PhD Student at IMS and 2024-2025 IMSSA Co-President Photo Credit: Stefan Aguiar

His interviews represent more than just data collection. He learns who these patients are as individuals and the kinds of interests they have—if they like to play games or if they like to hike.

Stefan seeks out these connections not only in his academic career, but outside of it as well. Throughout his undergraduate degree, between courses, work, and the long commute from Vaughan to downtown Toronto, Stefan spent most of his time in the library, the lab, or on transit. When he entered graduate school, he knew he wanted a change.

During his orientation, Stefan was convinced to join UofT Talks, where he helped organize a student-led conference on nutritional science. Kyla Trkulja, the Graphic design by Anaiah Reyes

IMSSA’s annual Warm Hands for Cold Streets event is particularly memorable for him. Every year, different research sites with IMS collect donations to provide warm clothing and essential items to those in the city who may otherwise lack access.

During his second year, Stefan helped lead the event, and to this day, it remains “one of the best experiences” he’s ever had, recalling how the people he met were always so genuine and grateful.

At the end of his second year, Stefan and Hamzah made their bid for co-presidents of IMSSA. Now, in his third year, Stefan is the co-president of UofT Talks alongside Anthaea-Grace Patricia Dennis, and is also co-president of the IMSSA with Hamzah Khan.

“

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What about the human aspect of it? People actually suffering with cancer—are we taking care of them?

The support Stefan receives through the people in his life has been essential in helping him manage all his current responsibilities. He cites his supervisor as one of the reasons he’s able to stay so involved—her encouragement has often pushed him to take that first step, and she goes “above and beyond” to make sure Stefan has what he needs both in terms of his academics and his career.

Despite the significant workload, it’s clear that it’s something Stefan enjoys—the people he meets, the connections he makes, and the laughs they share keep him going. Stefan hopes to continue making these connections and pursue a career in palliative care and oncology by pursuing an MD specializing in these fields in the future.

“It’s so precious, and I’m so grateful that I get these opportunities with people, and that’s how I know that’s what I want to do.”

All the additional responsibility keeps Stefan’s day-to-day busy with endless texts and emails about event logistics. That’s without even mentioning the many side projects he’s working on within IMS, from creating a web app to a methodology seminar—which may turn into a course in the future!

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ALUMNI SPOTLIGHT

Bridging the Gap Dr. Mikaeel Valli’s Journey from IMS to the Pharmaceutical Industry

By Lielle Ronen

W

ith career options for PhD graduates broadening beyond those in academia, experiences that prepare them for the diverse roles they can take on are essential. Recently, I got the chance to sit down with Dr. Mikaeel Valli, 2022 IMS alum and previous co-editorin-chief for the IMS Magazine, to hear about how he pivoted from academia to industry—a move being considered by an increasing number of graduate students. Dr. Valli brings his journey full circle from previously leading the IMS Magazine to now sharing his insights with its readers. Reflecting on his path from academia to the pharmaceutical industry, Dr. Valli highlighted how his early fascination with science and patient care shaped this transition.

Dr. Valli’s journey into science and research was deeply personal. As a child, he received a cochlear implant—a hearing prosthesis—which shaped his early interactions with healthcare workers and industry professionals. This experience gave him a better understanding of the impact of medical innovation on people’s lives and sparked his interest in the biological mechanisms of cognition and perception, leading him to explore neuroscience. Dr. Valli credits this pathway with guiding him towards pursuing a career where he could contribute to advancing medical knowledge and improving patient outcomes.

This early fascination with neuroscience eventually led Dr. Valli to complete his

PhD at IMS where his research involved conducting analyses on brain image scans of Parkinson’s disease patients under the supervision of Dr. Antonio Strafella. Towards the end of his PhD, Dr. Valli realized that he wanted to pursue a path in the pharmaceutical industry, which enabled him to capitalize on his previous work and research experience while providing support to patients and their families.

Dr. Valli credits the many volunteer and leadership opportunities within IMS that have helped him transition to and succeed in his current role in the pharmaceutical industry as a medical writer at IQVIA. Dr. Valli was involved with the IMS Magazine, where he started as a photographer and journalist in 2016 and was eventually promoted to co-editor-in-chief from 2021-2022. “I like the thrill of meeting different people and interviewing them,” Dr. Valli noted while reflecting on his experiences. “You meet different people, and hearing their perspectives just opens your horizons, and that encouraged me to take on more and just be entrenched in the feature article side of the magazine.” As a co-editor in chief, Dr. Valli was able to increase the magazine’s production rate back to quarterly issues post-pandemic, as well as streamline internal organization through the use of Discord to increase efficiency. This experience taught Dr. Valli leadership, project management skills, and helped him grow as a writer. “It’s certainly given me a lot of opportunities

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to learn and grow in terms of writing for different audiences, understanding who the audience is and being able to tailor the messages,” he explained.

Throughout his PhD studies, Dr. Valli participated in several professional development initiatives, including the Industry Team Case Study program organized by the Life Sciences Career Development Society (LSCDS). This opportunity enabled Dr. Valli to work on an industry case study collaborating with fellow grad students mentored by a pharmaceutical industry professional on a simulated project in regulatory affairs which sparked his interest in the pharmaceutical industry. These experiences gave Dr. Valli a practical understanding of industry workflows and allowed him to determine that this pathway was right for him.

After setting his sights on a pharmaceutical industry role, Dr. Valli completed his graduate diploma in Pharmaceutical & Healthcare Management and Innovation at Queen’s University following his PhD from IMS. As part of the program he was placed in a medical affairs associate role at Eisai Canada which solidified his foundational understanding of the pharmaceutical industry. In this role, he gained hands-on experience about how scientific research is translated into real-world therapies, regulatory processes, and clinical applications.

ALUMNI SPOTLIGHT

the oncologist in a scientifically fair, balanced, and compliant way,” Dr. Valli explained as an example.

Dr. Mikaeel Valli 2022 IMS alumnus and current medical writer at IQVIA Photo Credit: Dr. Mikaeel Valli

Dr. Valli has capitalized on these skills in his current role as a medical writer at IQVIA, a provider of biopharmaceutical development, professional consulting, and commercial outsourcing services.

IQVIA primarily specializes in Phase I-IV clinical trials, laboratory and analytical services, and investment strategy and management consulting.

Dr. Valli frequently applies the scientific communication skills that he developed while working on the IMS Magazine, for example, to translate knowledge from publications to the broader prescribers of those novel therapies. “If we are working on a project that is trying to highlight a new drug that treats patients in oncology, we would tailor and produce materials that translate that knowledge of the publication to Graphic design by Jeah Kim

more you can use them as leverage for success beyond your PhD.”

Beyond summarizing safety and efficacy data, this also means tailoring the content to the needs of different specialists, ensuring that general practitioners, pharmacists, and other healthcare professionals receive the most relevant and accessible information for their roles. One of the aspects Dr. Valli enjoys most about his current position is the opportunity to bridge the gap between research and clinical application. Whether that involves using clinical trial protocols and CSRs (clinical study reports) to develop manuscripts, abstracts and posters; or using manuscripts to develop training materials for pharmaceutical teams (via infographics or slide decks) or educational materials for healthcare professionals, he is able to make complex scientific information clear and accessible.

For Dr. Valli, the most rewarding part is knowing that his work helps different healthcare professionals make informed decisions about new therapies to ultimately improve patient care.

Finally, when asked about any advice he had for students looking to make the change from academia to industry, Dr. Valli stresses the importance of always networking and looking for any occasion to work with industry partners to “get a flavour of these different opportunities.

And because of those industry experiences that you get early on, the

Dr. Valli’s advice on transitioning to industry can be summarized by three main points. First, develop transferable skills during graduate studies, such as leadership, communication, and teamwork, as these are just as important as technical expertise.

Second, continuously refine your scientific communication skills to effectively tailor and convey scientific data to any audience—an invaluable skill in any career path. Lastly, take the time to network and learn about different roles in industry through internships, informational interviews, and professional organizations—Dr. Valli suggests that students “should explore and read about the different roles within the pharmaceutical industry with an open mind, [and] appreciate different roles and the impact that they potentially have.” Overall, our discussion highlights that the field of medical research is vast, and there are many opportunities to impact healthcare both within and outside traditional academia. Dr. Valli’s journey exemplifies how diverse career paths in the scientific field can all offer a way to make a difference in patients’ lives.

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FACULTY SPOTLIGHT

Dean Lisa Robinson’s Ever-Growing Spheres of Influence: Leading the Future in Kidney Care, Scientific Discovery, and Youth Mentorship

By Kristen Ashworth

D

r. Lisa Robinson took the helm as Dean of the Temerty Faculty of Medicine last year, becoming the second woman to lead the faculty in its history at the University of Toronto.

Her appointment in December 2023 was preceded by a multifaceted career as a pediatric nephrologist and kidney disease researcher, as well as a dedicated leader in the broader community. In this special Faculty Spotlight feature of our Spring 2025 issue, IMS Magazine had the privilege of speaking with Dr. Robinson to gain deeper insight into her distinguished career and the pivotal foundations that led to her current role as Dean.

Dr. Robinson’s academic journey began at the University of Toronto where she completed her medical education. She recalls that one of her final clerkship rotations–the pediatrics rotation–was particularly defining for her career. It was during this time that she established a deep passion for working with children and their families. After obtaining her medical degree, she pursued an internship in Internal Medicine at Toronto General Hospital, followed by a Pediatrics residency at the University of Western Ontario, then a Pediatric Nephrology fellowship at Duke University. Her decision to sub-specialize in nephrology came from a combination of her innate draw to this area of biology, in addition to strong mentors that guided her interests, including Dr. Mitchell Halperin in Toronto and Drs. John Foreman and

Del Wigfall at Duke. She reflects, “They really opened my eyes to the beauty of the kidney.” Dr. Robinson further explains what attracted her to nephrology stemmed from its logical and structured nature: “In nephrology, what I found is that, if you understand the physiology, then you don’t have to memorize very much. You can derive pretty much everything that you’re trying to measure and assess. [...] Those things really appealed to me, and putting together nephrology and pediatrics–that’s how I ended up doing what I do.”

Dr. Robinson is now a staff physician in the Division of Nephrology at The Hospital for Sick Children (SickKids), a senior scientist at SickKids Research Institute, and holds a Tier 1 Canada Research Chair in Vascular Inflammation and Kidney Injury. Her research interests focus on acute kidney injury and chronic kidney disease—a condition that, she emphasizes, “is one of the leading causes of illness and death worldwide.” As it pertains to optimizing and advancing how we treat chronic kidney disease, Dr. Robinson is interested in the role of the immune system. Her lab team investigates the mechanisms by which the immune system influences both the transition of acute kidney injury to chronic disease, and, conversely, the immune system’s role in repair. It is through these insights that her team has been able to identify candidate molecules to be used therapeutically.

This research has guided Dr. Robinson to reach translational heights over the

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past few decades in the field of kidney transplantation. Understanding the way in which key immune molecules (and other signalling molecules) function in repair after acute kidney injury can inform the approach to refine successful kidney transplantation, especially with injured donor grafts.

In collaboration with Dr. Markus Selzer, IMS faculty member and transplant surgeon at Toronto General Hospital, Dr. Robinson is leading a project with the ultimate goal of expanding the pool of human donor kidneys eligible for use in kidney transplantation. She describes an example of an ineligible donor kidney as one with prolonged acute ischemic injury.

Dr. Robinson’s team is exploring ways to revive such donor kidneys so they can be used for transplantation. To study this, they use Normothermic Ex Vivo Kidney Perfusion (NEVKP) in a pig model of transplantation.

“What we have found using this model,” Dr. Robinson explains, “is that [we can] take kidneys that are profoundly injured– and would never have been considered in the setting of transplant–and ‘buff them up’ so that they can work in transplant.”

The team aims to harness the molecular and cellular mechanisms involved in restoring kidney function and apply these in the context of preservation for damaged donor kidneys. Pathways of mitochondrial metabolism are of particular importance in preservation. AP39 is a mitochondrial stabilizer and enhancer in this pathway

DIVERSITY IN SCIENCE

Upon reflecting on the translational aspects of her research, Dr. Robinson emphasizes the significant role her patients play in helping to inform new directions for her work: “Sometimes the things that we think are the most relevant are actually not the most relevant things that patients and their families are thinking about. It’s really important that they be included in all aspects of our studies, from the conception to the execution, to the interpretation.”

Dr. Lisa Robinson MD, FRCPC, FASN, FCAHS Dean, Temerty Faculty of Medicine Professor, Institute of Medical Science Senior Scientist, SickKids Research Institute Staff Physician, Division of Nephrology, SickKids

Photo Credit: Erin Howe

that the team has explored. “We were able to use [AP39] in these models and take kidneys that were seriously injured and revive them, so they were suitable for transplant.” She highlights that one of the most exciting outcomes of this work was moving from bench to bedside. Recently, the team of Dr. Selzner and Robinson conducted a patient pilot study at Toronto General Hospital demonstrating the feasibility of NEVKP in the setting of kidney transplantation.

Graphic design by Bonnie Wang

In addition to the impact she makes on youth both in her clinic and through her research, over the past two decades, Dr. Robinson has founded two landmark scientific outreach programs: Kids Science and the Student Advancement in Research (StAR) Program. Based at SickKids, both programs aim to bring hands-on research experience to middle- and high-school students from priority neighbourhoods in Toronto and Northern Ontario. These programs have had far-reaching effects, with over 40,000 students participating in Kids Science since its founding in 2006, and more than 100 high school students completing the StAR Program’s fully funded six-week research internship since its founding in 2014. Beyond the numbers, Dr. Robinson reflects on the deeper impact these programs have made, stating that the students often form invaluable and lasting connections–the peers they meet become lasting friends, the graduate students they work with become enduring mentors, and the faculty with whom they interact

create the foundations of an important professional network.

Dr. Robinson finds grounding in her work at SickKids–whether in clinic, research, or outreach–as she takes on the responsibilities in her role as Dean. When asked what continues to drive her, she reflects “I’ve always been motivated by, how can I have impact, given my sphere of influence?” She adds, “I think your sphere of influence changes as your career progresses, too. Those opportunities for leadership positions and new challenges were pivotal moments because they showed me, in real time, that you can have a broad impact through these different systems and networks.”

For students at the Institute of Medical Science, these sentiments, and Dr. Robinson’s journey as a whole, exemplifies the power of mentorship and leadership— both personally and professionally—to expand our own spheres of influence. As our paths through IMS and beyond evolve, so do the ways in which we can lead, innovate, and drive meaningful change.

By passionately caring for and learning alongside her patients; by leading groundbreaking discovery and translational research in kidney transplantation; and by building up the next generation of scientists and clinicians, Dr. Robinson is a scientific and community trailblazer, and a true role model for all of us at the Temerty Faculty of Medicine.

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 39

DIVERSITY IN SCIENCE

From Vulnerability to Visibility:

The Pandemic’s Impact on Autoimmune Communities

By Mia Feldman

A

utoimmune diseases, such as Crohn’s disease, rheumatoid arthritis (RA), and lupus, are a class of conditions in which the body’s immune system mistakes its own healthy tissue for foreign invaders, leading to severe inflammatory reactions. It is well established that individuals with autoimmune diseases are at high risk of adverse response to infections; back in 1953, a landmark study found that among a cohort of RA patients who had passed away, infections were the cause of death in 25% of the cases.1 In 1976, the Union of the Physically Impaired Against Segregation and the Disability Alliance premised the social model of disability, distinguishing between impairment, the loss or abnormality of a physiological function, and disability, the restriction to perform tasks of activities the same way an able-bodied person can.2 For example, if a student uses a wheelchair and their school does not have a ramp, they cannot enter the building, resulting in a disability. The inability to climb stairs is an impairment, but it only becomes a disability when the environment prevents the student from accessing the building. Based on these definitions, it becomes clear that the extent and nature of one’s “disability” is contingent on their environment. The pandemic

drastically altered our environment, and the social model of disability can be used to understand the stories of our community members living with autoimmune conditions.

I heard the stories of three young adults living with autoimmune diseases during COVID19: Maryam Younis, Kiko Huang, and Mycala Casselman.

The early stages of the pandemic were terrifying for everyone. Little was known about how the virus was transmitted and what the early symptoms looked like, leaving many anxious and afraid.

Notably, these changes amplified barriers and challenges for individuals with autoimmune conditions. Maryam Younis, a recent University of Toronto (U of T) graduate, felt especially anxious when COVID-19 began. She explained that she was scared about how her body would react if she became sick and was constantly on high alert. Younis was also directly impacted by the spread of COVID-19 misinformation. Starting in March 2020, President Donald Trump made unsubstantiated claims at press conferences and on social media about how hydroxychloroquine may be used to treat COVID-19.3 Younis takes hydroxychloroquine to treat her condition and worried that panicked masses would have hoarded the drug she needs.

Thankfully, she was able to maintain access to her medication, but the uncertainty regarding the future of her access to care placed a significant burden on her mental health.

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Kiko Huang, a graduate student at U of T’s Institute of Medical Science, also expressed a change for the worse in her access to healthcare during the pandemic.

Huang has juvenile idiopathic arthritis and chronic inflammation throughout her body, including in her eye. This condition is called “uveitis” and is treated with glucocorticoids. A side effect of the treatment is increased ocular pressure, which must be monitored closely by an ophthalmologist. Prior to the pandemic, Huang would visit her ophthalmologist monthly. However, during the pandemic, she didn’t visit the specialist for nearly a year, and as a result, developed glaucoma in her right eye. Amazingly, Huang’s graduate research focuses on utilizing high-dimensional healthcare usage and billing data to guide health policy for the treatment of glaucoma. Her commitment to helping others is truly admirable.

The restricted access to care and widespread misinformation disproportionately impacted those with autoimmune diseases, which can be understood as a disabling consequence of the pandemic. However, that is only part of the story. Mycala Casselman is a recent graduate from Brescia University College with double honours in Psychology and Disability Studies. She is currently working at an early education centre focusing on artistic expression and sensory exploration.

Casselman explained to me that the pandemic has changed social consciousness about the spread of disease, shifting norms to create a more accessible environment for those with autoimmune conditions.

TRAVEL BITES

Those with autoimmune disease must be hypervigilant about contracting an infection. Casselman described that “weirdly, having an autoimmune disorder for my whole life prepared me for COVID-19.” Typically, the responsibility to prevent infection lies solely on those with autoimmune impairments, but this is changing. Both Huang and Casselman explained to me that at the height of the pandemic, their roommates went to great lengths to avoid breaching their “bubble” and increased masking and handwashing to limit the spread of COVID-19. It has become more commonplace to wear a mask on public transportation or to stay home from work if you are feeling sick.

These methods are not only to prevent oneself from becoming ill but to protect the health of those around us. There has been a reckoning in the public of a shared responsibility to keep each other safe. A shift in these norms creates a safer environment for everyone, including those with autoimmune conditions.

This social shift not only altered individual behaviour but also opened doors for accessibility opportunities via workplace policy changes. Reduced workplace accessibility poses a major barrier for individuals with impairments, as many employers fail to provide necessary accommodations. This inaccessibility becomes a disabling consequence, particularly for those with chronic conditions who face unequal access to employment opportunities. However, as Casselman put it, “COVID-19 offered Graphic design by Yu-Wen Jan

up so many accessibility opportunities,” including in the workplace. The mass adoption of remote and in-person hybrid models of work was initially put in place to encourage employees to stay home if they felt sick. But now, working from home is more commonplace. Younis explained that she has the option to work from home or to go into the downtown office, providing adaptability for days when she feels unwell.

Flexible work options show how inclusive policies can make workplaces more accessible for individuals with impairments.

The COVID-19 pandemic has had profound impacts on society, and we will feel its implications for generations to come. The long-term damage to our mental and physical health is undeniable.

However, a less expected outcome of the pandemic has been a change in public awareness of how infections spread and the shared responsibility we have to keep each other healthy. Even though the WHO declared the pandemic over in 2023,4 practices implemented during COVID19 to prevent the spread of infectious diseases are still in place today. From mask-wearing to enhanced sanitation protocols, many of these measures have become a lasting part of daily life to reduce the spread of the flu, colds, and other infections. These measures create a more accessible environment for those with autoimmune conditions, who must always be attentive to their health. The prevalence of autoimmune conditions has not changed as a product of COVID-19; however, changing social conditions that

favour accessibility means autoimmune impairments may become less disabling, and our world becomes more inclusive.

References 1. Cobb S, Anderson F, Bauer W. Length of life and cause of death in rheumatoid arthritis. N Engl J Med. 1953; 249(14):553-556.

2. Union of the Physically Impaired Against Segregation and the Disability Alliance. Policy statement [pamphlet]. London (UK); 1976.

3. Boseley, S. Hydroxychloroquine: Trump’s Covid-19 ‘cure’ increases deaths, global study finds. The Guardian. 2020. Medical Research. Available from https://www.theguardian.com/science/2020/may/22/hydroxychloroquine-trumps-covid-19-cureincreases-deaths-global-study-finds 4. UN News. WHO chief declares end to COVID-19 as a global health emergency; 2023 [cited 2025 February 4]. Available from https://news.un.org/en/story/2023/05/1136367

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 41

BOOK REVIEW

The Anxious Generation:

How the Great Rewiring of Childhood Is Causing an Epidemic of Mental Illness

By Rachel Lebovic A goal of mine for 2025 was to read more, which was driven by the intention to find some tech-free hobbies. As a member of Gen Z who grew up immersed in technology, I’ve decided my life needs more variety than what my computer, phone, and TV can offer, so I made a “to read” list for 2025. Not surprisingly, as a PhD student studying suicide prevention and youth mental health, The Anxious Generation by Jonathan Haidt made it to the top. I suspect that Haidt, a social psychologist at New York University (NYU), would be thrilled to learn this was the path I took to his book. Focusing on Gen Z, referred to as “the anxious generation,” Haidt tries to understand the dramatic rise of mental illness my generation has experienced. His suggested culprit: smartphones.

Haidt begins the book by presenting data from multiple countries demonstrating the youth mental health crisis, highlighting 2010-2015 as the critical period. In these years, rates of mental illness–specifically depression and anxiety–rose dramatically for young people. While this surge appears stark, Haidt proposes that it was the consequence of years of a changing landscape ignited by an inciting event.

This changing landscape, which Haidt refers to as “the great rewiring” is the result of the transition from a playbased to a phone-based childhood, altering how youth develop socially and emotionally. Hadit describes how society experienced a shift towards fear, which

led to the overprotection of kids in the physical world around the turn of the new millennium. He describes children as “inherently antifragile,” meaning they need to face failure and challenges to grow and develop resilience. The overprotection of kids in the physical world, which can include not allowing kids to walk to school alone or play contact sports, deprives children of the opportunity to experience adversity vital to the development of their antifragility. Instead, the belief that they are incapable is instilled, which can lead to an anxious disposition. Simultaneously, they are being introduced to the virtual world where they are, ironically, often under-protected. In the late 1990s and early 2000s as technology became widespread, there was little understanding of its impact on the developing mind, and consequently, little regulation.

The rise in mental illness is undeniable.

I see it in my research, and as a member of “the anxious generation,” I see it in my peers. Haidt presents a thought-provoking and convincing explanation for this rise.

While his solutions seem promising, I question their feasibility. Perhaps we can meet in the middle. If you are looking for a push to change your technology use or want insight on how to prevent your children from falling into the same problem, this is an interesting book for you.

References 1. Haidt J. The Anxious Generation: How the Great Rewiring of Childhood Is Causing an Epidemic of Mental Illness. Penguin; 2024.

Yet, as these societal changes were happening, rates of mental illness remained stable. It wasn’t until 2009 when the catalyst was introduced, the smartphone. This invention allows youth to have technology with them at all times, enabling constant access to social media and video games. This ushered in the full transition away from a play-based childhood to a phone-based childhood.

It was at this time a rise in mental illness became apparent. In the last section of the book, Haidt shares his proposed solutions including no phones until high school, no social media until 16, and increased independence for youth.

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Graphic design by Anaiah Reyes

TRAVEL BITES

By Kowsar Teymouri packed my days with unique learning.

ISPG is special as it provides an excellent avenue for scientists to collaborate through Psychiatric Genetics Consortium groups and combine their data to conduct genome-wide association studies with impressive numbers of samples, allowing for novel insights with strong statistical power to be made.

The Jewel at the Changi International Airport Photo Credit: Kowsar Teymouri

I

t was a mid-July afternoon, and I was busy wrapping up my week when I received an email from the International Society of Psychiatric Genetics (ISPG) with the subject’s first word reading “Congratulations”! My heart skipped a beat–I had received the Early Career Investigator Program award to attend the World Congress of Psychiatric Genetics (WCPG) in Singapore! This was an absolute dream come true.

My husband and I made sure to plan for a few extra days beyond the conference so we would have time to explore Singapore together. We spent one day wandering through the vibrant neighbourhoods of the city, admiring its stunning architecture.

Chinatown, with its bustling street market and irresistible tropical fruit stands, was a unique experience–it has a rich cultural heritage and is home to the famous Buddha Tooth Relic Temple, as well as the beautiful Sri Mariamman Temple, the oldest Hindu temple in Singapore.

Graphic design by Yu-Wen Jan

Photo Credit: Kowsar Teymouri

breathtaking nature trails. Matching the genetic theme of the conference, we walked through the double helix bridge to get to Marina Bay, which gives you a perfect angle to see the best that Singapore has to offer: the famous Marina Bay Sands, the Gardens by the Bay, the ArtScience museum, and the Merlion statue–the halflion, half-fish symbol of Singapore.

One thing that surprised me about Singapore was the language. Singaporeans speak “Singlish”–a unique local dialect that combines English with words and phrases from Malay, Mandarin, and Tamil.

It sounds Chinese, but if you pay close attention, you can catch the English!

Singapore was everything I had always imagined and more. Once I stepped into the Changi International Airport, I was blown away. The airport is home to the Jewel, an entertainment complex with the world’s tallest indoor waterfall surrounded by lush greenery and botanical terraces. I was mesmerized by its magic!

WCPG is one of my favourite conferences, as it closely aligns with my research on the genetics of schizophrenia. It gathered psychiatric geneticists from around the world to share the most recent advancements in methodologies and exciting findings in the field, which

The Sri Mariamman Temple, the oldest Hindu temple in Singapore

The Marina Bay Sands and ArtScience Museum Photo Credit: Kowsar Teymouri

The next day, we hopped on the famous Hello Kitty cable cars to visit Sentosa Island, where we walked through the

This was one of the most unforgettable trips of my life. I received valuable career advice from a remarkable mentor at WCPG and connected with top researchers in my field. And, of course, Singapore was the perfect content opportunity for my travel blog!

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 43

PAST EVENTS

IMS Winter Party – A Night to Remember

By Sara Corvinelli

O

n December 13th, the IMS Winter Party took a step back in time at the Centre for Social Innovation (CSI) Annex. IMS students ditched their lab coats and embraced the nostalgic vibe of Old Hollywood, with students walking the red carpet and claiming their star on the Institute of Medical Science Student Association (IMSSA) Walk of Fame!

The Winter Party is a beloved year-end tradition, hosted by the IMSSA Vice Presidents and the IMSSA party planning committee. This year’s organizers, Elsa Salvant and Megana Thamilselvan, dedicated themselves to making an evening to remember. The committee’s hard work was shown in the details, from the dazzling decor to activities that kept guests entertained the entire night.

The evening was made to feel extra glamourous with special guests, including IMS Associate Director, Dr. Lucy Osborne, who joined in on the festivities of the night. Faculty presence reinforced the sense of community that IMS brings about to make it a celebration for all.

The party offered something for everyone.

From blackjack tables for guests to try their luck, to the relaxing ambience of live music by Hart House Jazz, there was surely no shortage of entertainment. I had fun competing in the trivia game, where we were able to test our knowledge of Old Hollywood films and stars. I couldn’t get on the podium this time around, but lucky for me, a PhD takes a few years, and I will be back to claim my prize in the years to come.

Food, the best part of any celebration, did not disappoint. Smokin’ Bones caterers provided a spread of gourmet appetizers and finger foods, allowing guests to enjoy delicious treats while socializing with friends and colleagues. As we all know, grad students love their food!

An exciting part of the evening for guests were the contests for best-dressed and celebrity impressions. Guests showed off their Old Hollywood-inspired fashion, and some of my peers revealed they have secret comedic talents worthy of Saturday Night Live. The winners received special recognition, but I like to believe everyone walked away feeling like a star.

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One of the most touching moments of the evening was the IMSSA Wellness Committee’s Holiday Card Making station.

Guests were able to take a break from the busy festivities to craft personalized holiday cards for residents at local longterm care homes. The activity was both fun and heartfelt, reminding us of the true spirit of the season in the joy of giving.

It was a quiet moment of reflection apart from the celebration, to which I felt truly grateful to be a member of this sweet and generous IMS family.

As the curtains closed for the night, it was clear the Winter Party was once again a hit!

IMS students were able to set aside their lab responsibilities and deadlines, and just take time to enjoy the company of great friends and colleagues. The event was a true testament to the dedication of those who organized it, and to the joy that comes from bringing the IMS community together.

I want to personally send a heartfelt thank you to Elsa, Megana, my fellow team of planners, and all those who assisted in making the night feel so special. Your efforts did not go unnoticed and are deeply appreciated. The memories we created will stay with us for years to come.

As we eagerly anticipate to the next big party, stay tuned for the exciting reveal of next year’s theme. If this year’s Winter Party was any hint to the future, it will surely be yet another night to remember!

Graphic design by Nichole Zhou

RAW TALK AD Follow us @rawtalkpodcast for updates, photos, and videos

Listen wherever you get your

New episodes available every other Wednesday

podcasts or at rawtalkpodcast.com

RAW TALK PODCAST Get started with some of our favourite episodes: EP 126

EP 103

EP 53

Lungs on Ice, Robots, and Harnessing AI

Raw Talk Roundtables: Underrepresentation in STEM

EP 99

EP 97

EP 102

Surgical Innovations:

Refugee Healthcare in Canada

Let’s Talk Grad School

Indigenous Perspectives on Health

Healthcare Behind Bars

IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 45

RAW TALK PODCAST

Closing the Gap: Addressing Barriers & Disparities in Access to Surgery

RAWTALK PODCAST

By Tiffany Chien

W

hen thinking about international public health, there is often emphasis on vaccinations, nutrition, and maternal and child health while overlooking surgery.

Tragically, nearly five billion people worldwide lack access to safe, affordable, and timely surgical care, a substantial increase from earlier estimates of two billion.1,2 This discrepancy arises from differing definitions of surgical access: the previous estimate is based on the total distribution of operating theatres, while The Lancet Commission on Global Surgery advocates for a more inclusive approach including high-quality, timely, and financially supported surgical and anesthesia care for all.1 Despite progress in global health, mortality and morbidity rates in Low- and MiddleIncome Countries (LMICs) continue to rise due to limited resources in surgical care. In many African nations, one person dies of surgically-treatable disease every two seconds.3 The challenges to surgical access are multifactorial, with structural,

“

cultural, and financial barriers being the primary hurdles patients face.4 Structural barriers include lack of trained personnel and equipment, with ~67% of households citing these as primary obstacles.4 Cultural barriers mainly involve distrust in medical systems and poor treatment quality.

Financial obstacles include treatment costs, lack of savings, and travel expenses.4 For instance, in regions like sub-Saharan Africa and Southeast Asia, travel costs prevent many patients from receiving cleft lip and palate surgeries.5 LMICS often lack adequate services such as essential equipment, infrastructure, and specialized expertise. Even with available resources, a shortage of trained personnel hinders appropriate and timely diagnoses.

To further complicate things, those that receive referrals still struggle with access to motorized transport, with many patients travelling more than 10 km to reach emergency care.6 Furthermore, many congenital conditions like cleft lip, palate, and craniosynostosis—a birth defect involving the premature fusion of the

[...] shifting to a decentralized patient recruitment strategy which targets rural populations with limited surgical access.

“

46 | IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY

skull—require timely surgical intervention.

Cleft lip and palate surgeries are typically performed on children from 3 months to 1.5 years of age to optimize feeding and speech development. Meanwhile, craniosynostosis repairs are best done before 4 months after birth to improve surgical outcomes and prevent pressurerelated long-term neuropsychological impairments.5-8 Unfortunately, in LMICs, the average age for a child’s first cleft surgery is 3.24 years, and those in economically disadvantaged areas tend to receive craniosynostosis consultation later, leading to delays in surgical intervention and poorer developmental outcomes.7,8 Financial catastrophe occurs when health expenditures exceed 10% of total household spending or surpass more than 40% of non-food spending, heavily impacting already vulnerable populations.9 Astonishingly, 33 million individuals globally experience financial catastrophe from surgery costs alone, while 48 million struggle with additional nonmedical costs, including transportation, lodging, food, and informal payments.9 While financial hardship is a concern for all income levels, LMICs are at particularly high risk due to the disproportionate inflation of surgical costs relative to household income. Patients in these areas are forced to make the trade-off between receiving treatment at the hospital, or, alternatively, facing impoverishment. Moreover, outof-pocket payments remain the primary means of financing healthcare in many

RAW TALK PODCAST

LMICs, and while health insurance programs have been introduced to reduce this burden, coverage remains limited and inconsistent.9,10 As such, access to surgical care remains severely restricted, leaving many unable to afford appropriate, and oftentimes, life-saving procedures.

What is being done to change the surgical landscape in LMICs in particular?

Non-governmental organizations (NGOs) play a vital role in addressing these gaps, providing over 50% of surgical services in some LMICs.11 Mercy Ships, for example, works in partnership with host LMIC nations to deliver free surgeries and offer training on hospital ships in sub-Saharan Africa.11 Many of the common types of surgeries performed are life-changing, including cleft lip and palate surgeries, tumour removals from the head and neck, surgery after burns, and correction of neglected limb deformities.11 Nevertheless, ship-based care is temporary, with limited long-term healthcare development, continuity of expertise, and sustainable post-operative support. Additionally, travel time and non-medical costs remain obstacles for patients in rural areas.

One way of addressing these challenges is shifting to a decentralized patient recruitment strategy which targets rural populations with limited surgical access.

For instance, a study in Madagascar found that decentralized recruitment Graphic design by Stefanie Jinyin Wang

reached poorer patients in remote areas who faced financial and logistical difficulties, ensuring care reached the most underserved populations.11 Global surgery is a vital component of a strong global health system and should be given higher priority for attention and resources. To do so, we need to actively address barriers and provide comprehensive systemic and patientcentred solutions. In addition to offering free services, developing country-specific selection strategies, such as actively seeking patients in rural areas, are integral for ensuring surgical care is accessible and available. Additionally, local communities, NGOs, and leaders should collaborate to identify those most in need, using routinely collected patient demographic information and economic status to assess progress in improving surgical care access.11 Hopefully, a better understanding of surgical need through research, policy, and advocacy will train the current generation of surgeons to adopt a more holistic, patient-focused approach, paving the way for more inclusive and sustainable surgical care worldwide.

Acknowledgements: To learn more about reconstructive surgery and access to surgery in a global context, we invite you to listen to the upcoming episode of Raw Talk Podcast on Reconstructive Surgery. Also, check out some interesting resources the team has compiled in the episode’s show notes on the

Raw Talk Podcast website. We would like to acknowledge the efforts and ideas of the rest of the episode team: Avni and Bellinda were Show Hosts on the episode. Anisa and Selina were our Content Creator and Promo respectively; Raina was our Audio Engineer; and Noor was our Executive Producer.

References 1. Meara JG, Leather AJM, Hagander L, et al. The Lancet Commission on Global Surgery Global surgery 2030: Evidence and solutions for achieving health, welfare and economic development. Lancet Commissions. 2015;386(9993):569-624.

2. Alkire BC, Raykar NP, Shrime MG, et al. Global access to surgical care: a modelling study. Lancet Glob Health. 2015;3(6): 316-23. doi:10.1016/S2214-109X(15)70115-4.

3. 2024: Mercy Ships doubles down efforts to bring surgical care and training to sub-Saharan Africa as studies pinpoint critical gaps in surgical, obstetric, and anesthetic care - Mercy Ships Africa [Internet]. Mercy Ships. [cited 2025 Feb 28]. Available from: https:// mercyships.africa/2024-mercy-ships-doubles-down-efforts-tobring-surgical-care-and-training-to-sub-saharan-africa-as-studiespinpoint-critical-gaps-in-surgical-obstetric-and-anesthetic-care/ 4. Yao CA, Swanson J, Chanson D, Taro TB, Gura B, Figueiredo JC, et al. Barriers to Reconstructive Surgery in low- and middle-Income Countries: A Cross-Sectional Study of 453 Cleft Lip and Cleft Palate Patients in Vietnam. Plast Reconstr Surg. 2016; 138(5):887e-95e. doi:10.1097/PRS.0000000000002656.

5. O’Brien PF, Teti SA, Dewar C, et al. Optimal timing of endoscopic sagittal suturectomy. J Neurosurg Pediatr. Published online February 21, 2025. doi:10.3171/2024.11.PEDS24272 6. Porto Junior S, Meira DA, da Cunha BLB, et al. Endoscopic surgery for craniosynostosis: A systematic review and single-arm meta analysis. Clin Neurol Neurosurg. 2024;242:108296. doi:10.1016/j. clineuro.2024.108296 7. Jolibois MI, Roohani I, Moshal T, et al. Sociodemographic Factors Associated with Delayed Presentation in Craniosynostosis Surgery at a Tertiary Children’s Hospital. Plast Reconstr Surg. 2024;12(8):18. doi:10.1097/GOX.0000000000006035.

8. Grimes CE, Bowman KG, Dodgion CM, et al. Systematic Review of Barriers to Surgical Care in Low-Income and Middle-Income Countries. World J Surg. 2011;35:941-50. doi:10.1007/s00268-011-1010-1.

9. Shrime MG, Dare AJ, Alkire BC, et al. Catastrophic expenditure to pay for surgery worldwide: a modelling study. Lancet Glob Health.

2015; 3 Suppl 2(0 2):S38–S44. doi:10.1016/S2214-109X(15)70085-9.

10. Hooley B, Afriyie DO, Fink G, et al. Health insurance coverage in low-income and middle-income countries: progress made to date and related changes in private and public health expenditure. BMJ Glob Health. 2022; 7(5): e008722. doi:10.1136/bmjgh-2022-008722.

11. White MC, Hamer M, Biddell J, et al. Facilitating access to surgical care through a decentralised case-finding strategy: experience in Madagascar. BMJ global health. 2017;2(3):1-6. doi:10.1136/bmjgh-2017-000427.

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IMSSA POSTER

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COMICS

The Serious Matter Author: Kiko Huang Illustrator: Emily Huang IMS MAGAZINE SPRING 2025 INFLAMMATION AND ALLERGY | 49

IMS RESEARCH ROUNDS AD

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