IMS MAGAZINE Winter 2020

THINK. LEARN. DISCOVER.

NEPHROLOGY ACUTE RENAL INJURY

New Proteins May Be Key to Protecting Kidney Tissue

PEDIATRIC KIDNEY DISEASE Understanding How Kidneys Are Formed

GENDER PAY GAP IN MEDICINE Why Are Female Surgeons Paid Less?

WINTER 2020

RAW TALK PODCAST

58 Our Aging Population Dr. Morris Moskovitch University of Toronto

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IN THIS ISSUE Raw Talk Podcast....................................... 2 Letter from the Editors............................... 4 Director’s Message.................................... 5 Contributors’ Page .................................... 6 Infographic................................................. 8 Features .................................................. 10 Biomedical Communications .................. 18 Viewpoint................................................. 20 Faculty Spotlight...................................... 28 Student Spotlight..................................... 30 Alumni Spotlight...................................... 32 Past Events .............................................. 34 Travel Bite ............................................... 38 Book Review ........................................... 39

MAGAZINE STAFF EDITORS-IN-CHIEF:

Beatrice Ballarin Natalie Osborn EXECUTIVE EDITORS:

Jonathon Chio Krystal Jacques Mikaeel Valli DESIGN EDITORS:

Roxanne Ziman (Director) Hang Yu Lin Janell Lin Chloe Ng Su Min Suh PHOTOGRAPHERS:

Krystal Jacques (Director) Mikaeel Valli Kenya Costa-Dookhan Nathan Chan SOCIAL MEDIA TEAM:

Sandy Lee (Director) Serina Cheung Cindy Ha Stephanie Hulme

JOURNALISTS & EDITORS:

Mashal Ahmed Laura Best Nadia Boachie Stacey Butler Serina Cheung Kenya Costa-Dookhan Sumaya Dano Alexa Desimone Yekta Dowlati Sonja Elsaid Shahrzad Firouzian Melissa Miljanovski Diana Hamdan Rehnuma Islam Gaayathiri Jegatheeswaran Zahra Khan Jason Lau Darby Lowe Erika Opingari Cricia Rinchon Janannii Selvanathan Natalie Simonian Mathura Thiyagarajah Mirkamal Tolend Alaa Youssef Shenhab Zaig

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By Janell Lin MScBMC CANDIDATE

Copyright © 2020 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 Chloe Ng

MScBMC CANDIDATE

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LETTER FROM THE EDITORS

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he start of a new year always brings new resolutions to help become our better self. For most of us, getting enough sleep, exercise, healthy food, and drinking more water are definitely on our wish-list. What do those healthy habits have in common?! Well, the answer is simple: it involves kidney function!

Often we don’t think about our kidneys in our daily routine, however, they play the important role of filtering our body fluids and secrete important hormones. Keeping hydrated not only rejuvenates your skin but also helps the kidney to stay healthy. And so we proudly present the Nephology issue.

Letter from the

Editors

The Winter 2020 issue of the IMS Magazine set out to discover the latest research developments Photo credit: Krystal Jacques in the world of nephrology. Starting with Dr. Richard Gilbert, who has dedicated his career as a clinician and researcher to identifying therapeutic strategies to prevent and treat chronic kidney disease. He tells us about understanding the link between diabetes and kidney function on his journey until founding the biotech company Firbotech Therapeutics. Next, read how Dr. Norman Rosenblum and colleagues are growing kidney organoids from patients’ urine cells in a huge step forward for individualized kidney treatments. He and his team are studying how malformations in kidney development contribute to kidney failure in children and adolescents. Dr. Christoph Licht tackles the issue of rare kidney disease caused by genetic conditions. He studies how the kidney’s vast microvasculature system is affected by overactivation of the complement system - the “ancient biology” that helps our immune systems distinguish foreign tissue from our own. Finally, read about Dr. Lisa Robinson’s work revealing the mechanisms that regulate immune cell trafficking to inflamed tissue in acute kidney injury. She’s identified naturally occurring proteins whose anti-inflammatory effects could be harnessed as a novel therapeutic to limit injury.

IMS students continue the evolution of our previous issue on Women’s Health to advocate for gender equality with a viewpoint on the gender pay gap in medicine. Towards a healthier lifestyle, they discuss the impact of medical wearables and the effect of cannabinoids as an alternative medicine. Lastly, they discuss the effect of monosodium glutamate (MSG) as a food ingredient in light of prejudice towards the Chinese community.

In this issue we highlight several exciting past events including our Summer Undergraduate Research Program with SURP Research Day, and our annual Ori Rotstein Lecture in Translational Research. It’s exciting to shine a light on a new member of the IMS faculty, Dr. Zhon Ping Feng, who is opening the IMS doors to more international collaborations. And finally, we have featured one of our super-involved student and her story: senior PhD candidate Laura Best. Be sure to check out our fun section: this issue’s travel bite brought us to South Korea! Or if you are looking for a good read for these cold winter days, we got you covered with the review of Educated!

As Co-Editors in Chief we’d like to acknowledge the team of dedicated students who spent their Christmas holidays making this issue a reality, and our photo this year includes the entire Exec Editor team. As Director of Distribution, Jonathan Chio is continually working to expand the reach of IMS Magazine throughout the Toronto community. Look for Director of Photography Krystal Jacques-Smith’s photos throughout the issue –she’s also organizing a professional workshop to help students hone their camera skills. And the fascinating infographic on page 8? It was written by Feature Director Mikaeel Valli, who coordinates the feature articles that accompany each issue’s theme. See page 6 for the writers behind this issue, and page 18 to learn about the fantastic Biomedical Communications Program that produces our stellar design team. We hope you enjoy this issue, and we’d love to hear from you: you can email us at theimsmagazine@gmail.com and visit our website at imsmagazine.com.

Happy 2020 and happy reading!

Natalie Osborne

Beatrice Ballarin

Natalie is a 4th year PhD student using neuroimaging and sensory testing to understand chronic pain under the supervision of Dr. Karen Davis. Outside the lab she loves to write about science and true crime. @NatalieRaeOz

Beatrice is an international PhD candidate in the laboratory of Dr. Michael Tymianski at the Krembil Research Institute, working on strategies to promote stroke recovery. Outside the lab she is an avid reader of non-fiction books (check them out in our Book Review section) and loves running. @BBallarina

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Director’s Message

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DIRECTOR’S MESSAGE

he start of a new year is a time to reflect on improving ourselves and reaching our goals. Here at IMS, we are always aiming for excellency, and we are looking for ways to improve. This past year we reflected on what we are doing well, and what we can do to improve over the next five years. This past November, The Potential Group facilitated collaborative and engaging planning sessions among our staff, faculty, and students to develop a new strategic plan.

Together with our Director of International Development at IMS, Dr. Zhong-Ping Feng, who is featured in this issue, we are opening our doors to more international students.

The IMS has identified diversity as a strategic priority, and key to success. There is no better example of this than the cultural mosaic that is Canada itself. We are committed to raising the next generation of doctorates, and therefore we have been working toward improving scholarships that are solely dedicated to our PhD candidates.

The theme of this issue, Nephrology, showcases the innovative work of IMS faculty Drs. Richard Gilbert, Norman Rosenblum, Christoph Licht and Lisa Robinson. They are focusing on understanding the pathogenesis of kidney disease from the genes up, and finding novel therapeutic solutions to issues, such as inflammatory injury after kidney transplantation, kidney fibrosis in diabetic populations, and congenital kidney disease in children and adolescents.

This current issue also highlights one of our popular yearly events: the Ori Rotstein lecture. For the first time, the panel discussion featured one of our student leaders, Laura Best, who joined in on the conversation alongside IMS alumnus Dr. David Hackam, Dr. Ori Rotstein, Dr. Shelley Boyd, Dr. Samantha Anthony, and Dr. Sunit Das. This year’s theme centered on our panelists’ diverse journeys into science and provided stimulating conversation!

I am taking this opportunity to remind IMS Magazine readers of the most important event of the year: IMS Scientific Day 2020. This year’s event will be held on Tuesday, May 26th at the Rotman School of Management and coincides with the release of the magazine’s spring issue. I encourage all students to participate in one of the numerous initiatives to present your data and to leverage this opportunity to gain valuable skills in scientific communication! For important information and deadlines, please refer to the website, or download our memo. I look forward to seeing your excellent work on display at this year’s Scientific Day 2020!

New students were warmly welcomed to the IMS at this year’s orientation, fully coordinated and executed by current IMS student leaders. Once again, welcome to our January 2020 recruits– I sincerely hope your first few months have been rewarding and memorable thus far.

Finally, I would like to thank IMS Magazine’s Editors-in-Chief, Beatrice and Natalie, all the editors, journalists, photographers, social media team, and design team for their excellent production this semester. Join us as we enter a fresh start, toward the creation of new knowledge and innovation. I hope you all learn something new and inspiring in this Winter 2020 issue!

Sincerely, Dr. Mingyao Liu, MD, MSc Director, Institute of Medical Sciencev

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CONTRIBUTORS

Winter 2020 Contributors The IMS Magazine is a student-led publication. IMS students are responsible for writing, editing, and photography, while MSc in Biomedical Communications (BMC) students create the design. Meet some of the writers for this issue below!

Mashal Ahmed is a 2nd year MSc

Laura Best is currently a PhD

Nadia Boachie is a 2nd year MSc

student at IMS, studying under the supervision of Dr. Stefan Kloiber and Dr. Isabelle Boileau. Her research employs neuroimaging techniques to learn more about the neurobiological mechanisms associated with anxietyspectrum disorders. Mashal is doublejointed and can twist her arm 540 degrees!

student with Dr. Isabelle Boileau at CAMH. Her work uses neuroimaging to investigate the involvement of the endogenous cannabinoid system in alcohol use disorder. Check out this issue’s student spotlight to learn more about her work and time with IMS!

IMS student studying the effects of cannabis on the brain under the supervision of Dr. Isabelle Boileau.

Her research uses neuroimaging techniques to assess changes in the brain of chronic cannabis users after approximately 1-week cessation. In her free time Nadia is passionate about cooking, baking, and painting.

Serina Cheung is a 2nd year

Kenya Costa-Dookhan is a 2nd

Sonja Elsaid is a 2nd year IMS Ph.D.

MSc student at IMS investigating treatments for castration-resistant prostate cancer under the supervision of Dr. Marianne Koritzinsky. In her free time, she is either planning her next vacation or being an avid consumer of Korean pop music.

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year MSc student in the IMS. She is supervised by Dr. Margaret Hahn and her work focuses on the mechanisms of and treatment interventions for antipsychotic induced weight gain among patients with severe mental illnesses. In her spare time, Kenya loves cycling and trying new restaurants.

student investigating brain function and cannabis use in individuals with social anxiety. Prior to going back to school, Sonja was a clinical research and medical communications professional with nearly 20 years of experience.

CONTRIBUTORS

Diana Hamdan is a recent MSc

graduate continuing her work on molecular mechanisms of immune cell trafficking in vascular inflammation with Dr. Lisa Robinson at the Hospital for Sick Children. Outside the lab, Diana is involved in initiatives that promote sustainable practices in urban environments.

Krystal Jacques is a 2nd year

IMS PhD student using human embryonic stem cells and lineage tracing mouse models to study the origins of pancreatic stem cells under the supervision of Dr. Derek van der Kooy. Outside the lab she is passionate about fine art photography, writing fiction, painting and running.

Instagram: Krystaljacques_

Natalie Simonian is a 1st year MSc

student at IMS. She is working under the supervision of Dr. Harry Janssen investigating the pathology behind Non-Alcoholic Fatty Liver Disease (NAFLD). In her free time she likes to spend time with family and friends, write short stories, and travel.

Instagram: _nataliesim

Jason Lo Hog Tian is a 2nd year

MSc doctoral stream student at IMS investigating the barriers preventing people living with HIV from seeking treatment under the supervision of Dr. Sean Rourke. He is committed to developing his scientific communication skills through writing for the magazine.

Tweet @JasonLoTweets

Mikaeel Valli is currently completing his PhD with specialization in neuroscience at IMS. He is working with Dr. Antonio Strafella and his lab using neuroimaging techniques to ultimately better understand the underlying pathophysiology of Parkinson’s disease. Check out Mikaeel’s travel-bite article about his experience visiting South Korea!

The IMS Design Team 2020

is a group of 2nd year students in the MSc in Biomedical Communications (BMC) program. Turning scientific research into compelling visualizations is their shared passion, and they are thrilled to contribute to the IMS Magazine. From left to right: Chloe Ng (visualsbychloe.com) Hang Yu Lin (hlin-visuals.com) Roxanne Ziman (roxanneziman.com) Su Min Suh (su-visual.com) Janell Lin (janell-lin.format.com/) IMS MAGAZINE WINTER 2020 NEPHROLOGY |

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INFOGRAPHIC

Kidney Disease in Canada

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INFOGRAPHIC

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FEATURE

Accelerating the Discovery of

Anti-Fibrotic Therapies for Chronic Kidney Disease

By Alexa Desimone

F

Dr. Richard E. Gilbert, an endocrinologist at St. Michael’s Hospital in Toronto, has dedicated his professional career to identifying therapeutic strategies for the prevention and treatment of chronic fibrotic disorders, focussing predominantly on CKD and heart failure. He is particularly interested in these disorders in the diabetic setting given that diabetes is present in approximately 30-50% of all patients with either heart failure or CKD. Dr. Gilbert is a Tier 1 Canada Research Chair in Diabetes 10 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

Growing up in Adelaide, a small city in South Australia, Dr. Gilbert completed his medical training at Flinders University.

Excited by the prospect of continuing in clinical medicine while also pursuing his research interests, he accepted an offer as a one-year lecturer at London University in London, England. As Dr. Gilbert described, “The salary was barely enough to live on but the opportunity it afforded me in the academic, social and societal spheres was immeasurable”. This was a pivotal moment in Dr. Gilbert’s career. Rather than staying on a predictable and linear path, he made a bold choice that would enrich his academic and life experiences.

Returning to Australia, he completed his medical fellowship and doctoral studies in the clinical and molecular aspects of diabetic kidney disease and established a highly productive research laboratory at St. Vincent’s Hospital in Melbourne, Australia. But it was time for Dr. Gilbert to broaden his horizons once again by seeking to do a sabbatical in Toronto where his wife, Susan, was from. Rather than offers for his intended sabbatical, Dr. Gilbert was invited to apply for newly available clinician-scientist positions at two University of Toronto institutions.

“Coming to a city with such great research, collegiality, and collaboration made the decision easy” said Dr. Gilbert. So, in 2006 he set up his laboratory and took

up his post at St. Michael’s Hospital as a clinician-scientist.

The pathogenesis of diabetic kidney and heart disease, encompassing both glucose-dependent and glucoseindependent pathways, requires a multifaceted approach to establish therapeutic strategies.⁶ In the kidney, fibrosis impairs filtration and tubular cell function, whereas in the heart, it impairs both systolic and diastolic function with stiffening and impaired contractility of Photo sourced from St. Michael’s Hospital

ibrotic disorders are becoming increasingly prevalent; they take many forms and are often life threatening. It is estimated that fibrosis accounts for almost half the chronic diseases afflicting industrialised countries.1 Chronic kidney disease (CKD) is one of the most devastating and common examples of fibrotic disease.2,3 In the kidney, fibrosis is characterized by the accumulation of extracellular matrix proteins, typically in the glomerulus and tubulointerstitium, which inevitably infringes on nearby structures, resulting in hypoxia, tubular atrophy, and inflammatory cell infiltration.4 With time, the formation of fibrotic lesions leads to irreversible end-stage kidney failure.

Unfortunately, four million Canadians are currently living with CKD, with the majority requiring dialysis or kidney transplantation.5 Despite its prevalence, therapeutic strategies targeting profibrotic mechanisms in CKD are lacking.

Complications, Professor of Medicine at the University of Toronto, and Head of the Division of Endocrinology at St. Michael’s Hospital/Unity Health Toronto.

DR. RICHARD E. GILBERT MD, FRCPC, FRACP, FACP, FASN, PhD Professor of Medicine, University of Toronto Head of the Division of Endocrinology, St. Michael’s Hospital Canadian Research Chair in Diabetes Complications

FEATURE

It’s possible to be a dedicated academic and devoted clinician, but to also be cognisant of the need to engage with industry and the business community in order to progress your ideas towards the clinic.

the left ventricle.⁷ While investigating the pathogenesis of fibrosis is of great interest to Dr. Gilbert, his real desire was to develop new therapies that could be used to treat patients. With this in mind, he co-founded a biotechnology company called Fibrotech Therapeutics which attracted NIH funding to progress its lead compound, FT011, into early human studies. In pre-clinical studies, FT011 has demonstrated anti-fibrotic and antiinflammatory properties that have shown to be useful in treating chronic heart failure associated with diabetic kidney disease.⁸ After Fibrotech was sold to Shire, a large, multi-national pharmaceutical company, Dr. Gilbert, believing that a single drug was unlikely to cure a complex disease process such as fibrosis, continued to investigate novel approaches to combat fibrotic disease.

In 2016, Dr. Gilbert along with three other co-principal investigators were awarded a $1-million Transformational

Diabetes Team Research Grant from the University of Toronto’s Banting and Best Diabetes Centre. This funding was used as the foundation for another endeavor to develop new anti-fibrotic therapies. Along with funding from MaRS Innovation and an investment from another biotechnology company, Evotech, Fibrocor Therapeutics began utilizing archival kidney biopsy tissue to uncover transcriptomic changes that are linked to fibrosis. One of the very first analyses of the data uncovered the discoidin domain receptors (DDRs), unique tyrosine kinase receptors that signal in response to nondiffusible collagens and have been shown to be upregulated in fibrotic diseases.⁹ Their team identified DDRs as a close correlate of declining kidney function and the extent of fibrosis. With the help of Evotech, Fibrocor’s drug development partner, they hope to develop inhibitors of DDR to treat, prevent, and possibly reverse fibrotic disease.

Images provided by Dr. Gilbert

A normal glomerulus (left) and an enlarged fibrotic glomerulus (right).10

Dr. Gilbert embodies the concept of bench-to-bedside medicine in its truest sense. With a strong background in basic research, he knew that his findings could benefit innumerable patients with CKD. He took it upon himself to try and turn his discoveries into therapeutic agents that help patients. “It’s possible to be a dedicated academic and devoted clinician, but to also be cognisant of the need to engage with industry and the business community in order to progress your ideas towards the clinic”, says Dr. Gilbert. He hopes to inspire young clinician-scientists to always look for opportunities that enrich your life experience as well as your professional life.

References 1. Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest. 2007;117(3):524-529.

2. Hewitson TD. Fibrosis in the kidney: is a problem shared a problem halved? Fibrogenesis Tissue Repair, 2012;5, S1:S14.

3. Canadian Institute for Health Research. Annual Statistics on Organ Replacement in Canada Dialysis, Transplantation and Donation, 2008 to 2017. CIHI Snapshot, December 2018. Available from:https:// secure.cihi.ca/free_products/snapshot-corr-2018-en.pdf.

4. Gilbert RE, Zhang Y, Williams SJ, et al. A purpose-synthesised anti-fibrotic agent attenuates experimental kidney disease in the rat.

PLoS One, 2012:7(10), e47160.

5. Manns, B., McKenzie, S.Q., Au, F., et al. The financial impact of advanced kidnet disease on Canada pension plan and private disability insurance costs. Can J Kidney Health Dis, 2017:4, 1-11.

6. Kelly DJ, Zhang Y, Hepper C, et al. Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continues hypertension. Diabetes, 2003:52, 512-518.

7. Yuen DA, Connelly KA, Zhang Y, et al. Early outgrowth cells release soluble endocrine antifibrotic factors that reduce progressive organ fibrosis. Stem Cells, 2013:31(11), 2408-2419.

8. Zhang Y, Edgley AJ, Cox AJ, et al. FT011, a new anti-fibrotic drug, attenuates fibrosis and chronic heart failure in experimental diabetic cardiomyopathy. E J Heart Fail, 2012:14, 549-562.

9. Borza CM, Pozzi A. Discoidin domain receptors in disease. Matrix Biol, 2014:34, 185-192.

10. Zhang Y, Connelly KA, Thai K, Wu X, Kapus A, Kepecs D, Gilbert RE. Sirtuin 1 Activation Reduces Transforming Growth Factor-β1– Induced Fibrogenesis and Affords Organ Protection in a Model of Progressive, Experimental Kidney and Associated Cardiac Disease.

The American journal of pathology. 2017 Jan 1;187(1):80-90.

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FEATURE

From infancy to adulthood:

A molecular look at kidney malformations

By Nadia Boachie

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ongenital anomalies of the kidney and urinary tract (CAKUT) are the most common form of malformation at birth, identified in over 1% of overall live births and accounting for up to 23% of overall birth defects. CAKUT represent the cause of 40-50% of pediatric end-stage renal disease worldwide.1 While some CAKUT are treatable-albeit with long term health consequences-others are extremely life threatening.2 UofT researchers are using genetically modified mice and human kidney organoids grown from patients’ urine samples to understand the molecular mechanisms underlying kidney disease. Their goal is to one day develop individualized treatments that target these molecular pathways in pediatric patients.

The causes of kidney failure vary from infancy to adulthood. Before age five, congenital malformations of the kidney and urinary tract are the leading causes. From ages five to 14, it is most commonly caused by nephrotic syndrome, systemic diseases, and hereditary diseases such as autosomal dominant polycystic kidney disease. At around 15 years to early adulthood, diseases that affect the glomeruli—tiny ball-shaped structures in the kidney composed of capillary blood vessels that are involved in the filtration of the blood to form urine— become the leading cause of kidney failure.3 With so many different contributors and causes of kidney failure in the pediatric population, researchers are trying to better understand the molecular mechanisms of kidney development that occur prenatally and postnatally, with a goal to treat patients.

The IMS Magazine had the pleasure of sitting down with Pediatric Nephrologist and Senior Scientist at The Hospital for

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Sick Children, Dr. Norman Rosenblum. He completed his MD at Dalhousie University and postgraduate clinical and research training at Children’s Hospital and Harvard Medical School, and has been conducting research in nephrology for his entire career as a clinician-scientist. Dr. Rosenblum set up his lab in 1993 and his first graduate unit appointment in 1995 was with The Institute of Medical Sciences (IMS).

Dr. Rosenblum began using mouse models as well as other experimental methods to ask three important questions; ‘How is formation of the kidney accomplished?’, ‘What are the cellular and molecular mechanisms underlying kidney malformation?’, and ‘How can we use human genetics and experimental nephrology to inform our understanding of kidney development and human disease?’

To address these questions, Dr. Rosenblum’s lab “focuses on different signalling pathways, both alone and together during the development of the kidney in the mouse” he explained.

Specifically, the lab looks at pathways controlled by Bone Morphogenetic Proteins (BMPs), Hedgehogs (Hh), and Wnt proteins during normal kidney formation and renal malformation.4 Hedgehog signaling has been of particular interest, as hedgehog proteins are important for tissue patterning and cell differentiation.

They also transduce cellular signals via the GLI protein family of transcription factors. “Everything we seem to touch, from how progenitor cells are differentiated to specific kidney elements, variation in nephron number, or interactions between different tissue elements - in whatever we inquire about, there seems to be a story about how hedgehog signaling is involved” says Dr. Rosenblum.

Photo by Nadia Boachie

DR. NORMAN ROSENBLUM, MD Pediatric Nephrologist at The Hospital for Sick Children Senior Scientist at The Hospital for Sick Children Professor of Pediatrics, Physiology, and Laboratory Medicine and Pathobiology at the University of Toronto In a 2018 paper published in Journal of American Society for Nephrology, Dr. Rosenblum and his collaborators used patients’ specimens and mouse models to better understand the pathogenesis of ureteropelvic junction obstruction, the most common form of congenital urinary tract obstruction. The mice in this study were genetically modified to be deficient for the Hedgehog target, Ptch1.

Rosenblum and collaborators analyzed obstructive ureteric tissue obtained from children with congenital intrinsic ureteropelvic junction obstruction and discovered that molecularly, these human samples were similar to what

FEATURE we are using human organoids as a way to model these things and inquire further into mechanisms of human disease” he adds.

This is an image captured and stained by members of Dr. Rosenblum’s lab.

It is a stitched wholemount kidney organoid generated from blood-derived induced pluripotent stem cells. DAPI (blue) marks the nuclei of all cells, WT1 (red) marks renal podocytes, and ECAD (green) marks distal tubular epithelial cells. was observed in Ptch1-deficient mice.

Their results demonstrate a Hedgehogdependent mechanism underlying urinary tract blockage. In another recent 2018 publication in Development, they found a mechanism by which Hedgehog-GLI signaling in Foxd1-positive stromal cells, via TGFβ signaling, controls the number of nephrons formed in the kidney.5 “We keep working at [hedgehog] because the story continues to unfold, in a very interesting way” he explains.

Dr. Rosenblum clarifies that experiments in mice are vital but are not the entire picture. “There are important differences in what happens in mice and what happens in humans. Same gene, same mutation, doesn’t look the same in terms of what the phenotype is in humans versus mice” he explains, “We really wonder why that is. So,

Recently, the Rosenblum lab and collaborators were able to isolate human urine cells (UCs) from pediatric urine specimens. These urine samples were reprogrammed into urinary induced pluripotent stem cells from which human kidney organoids were generated.6 “When you take urine, even small amounts, and put it on a plate, epithelial cells grow. What you then can do is treat those cells with plasmids that contain four factors that were described in Nobel winning work7 to convert the cells from a differentiated cell to a pluripotent cell. Once you have that pluripotent cell, then you can direct that cell to differentiate in various ways using other factors” Dr. Rosenblum explained. He further elaborated that “even though [the organoid] is a very immature kidney tissue, it is human tissue, and [it is] from the very patients that we would be interested in.”

This is a big step in the right direction for individualized kidney treatments.

There are still major challenges in this field of research. A healthy and functioning kidney requires formation of a critical number of nephrons; they are necessary to drain urinary filtrate into the ureter towards the bladder. A large body of epidemiological studies have shown that the number of nephrons that you are born with varies tremendously in the population.8 There may be as much as a six-fold difference between individuals. Some may be born with 200,000 nephron elements, and others with about 1.8 million. “Clinically, we don’t even have a method to measure the number of nephrons elements an individual is born with” explains Dr. Rosenblum. This poses an issue when trying to identify infants that may have potential issues with kidney development in the future. Dr. Rosenblum’s lab is trying to find non-invasive ways to determine nephron number. “We are aiming to determine biomarkers that tell

us this information, for example, based on their number of nephrons we’ll be able to say ‘well this person may be at higher risk [for kidney disease/malfunction] so we should be aware of it,’” he explains.

Dr. Rosenblum’s impressive list of publications and his successful career as a clinician-scientist seems to be made possible because of his well-roundedness.

Outside of the lab, Dr. Rosenblum is a seasoned cello player, an instrument he has played since the age of 14. His passion for classical music drives him to continue to practice and play with other musicians to this day. He wants students and young researchers to know that in their professional careers, they should go after what they are passionate about. He also advised that researchers “find other things to do which cater to other parts of you,” and to spend time on that too. Lastly, he added that “the management of time and energy is a big skill and maybe one of the most important skills that people have. Just because you work long doesn’t mean you work well.” These pieces of advice seem to be how Dr. Rosenblum continues to thrive in his scientific endeavours.

References 1. Sanna-Cherchi, Simone, Pietro Ravani, Valentina Corbani, Stefano Parodi, Riccardo Haupt, Giorgio Piaggio, Maria L. Degli Innocenti et al. “Renal outcome in patients with congenital anomalies of the kidney and urinary tract.” Kidney international 76, no. 5 (2009): 528-533.

2. Kidney Disease in Children [homepage on the internet] National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Health and Human Services, 1 Mar. 2014, Available from: http//www.niddk.nih.gov/health-information/kidney-disease/ children.

3. National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. United States Renal Data System.

1993 Annual Data Report. 1993 Mar: 55-67.

4. Norman Rosenblum Lab [homepage on internet]” Rosenblum Lab, Available from: http//lab.research.sickkids.ca/rosenblum/.

5. Rowan CJ, Li W, Martirosyan H, Erwood S, Hu D, Kim YK, Sheybani-Deloui S, Mulder J, Blake J, Chen L, Rosenblum ND. Hedgehog-GLI signaling in Foxd1-positive stromal cells promotes murine nephrogenesis via TGFβ signaling. Development. 2018 Jul 1;145(13):dev159947.

6. Mulder J, Sharmin S, Chow T et al. Generation of infant-and pediatric-derived urinary induced pluripotent stem cells competent to form kidney organoids. Pediatric Research. 2019 Oct 19:1-0.

7. Takahashi K, Okita K, Nakagawa M, Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nature protocols. 2007 Dec;2(12):3081.

8. Wang X, Garrett MR. Nephron number, hypertension, and CKD: physiological and genetic insight from humans and animal models.

Physiological genomics. 2017 Jan 27;49(3):180-92.

Dr. Rosenblum’s lab characterizes how healthy kidneys develop in order to understand what can go wrong in patients with congenital anomalies. This is an image showing a mouse embryonic kidney histological section stained for DAPI (blue) which marks the nuclei of all cells, PBX1 (pink) which marks stromal progenitor cells, SALL1 (green) which marks both stromal, and nephrogenic progenitor cell and the orange cells in the periphery are both Sall1+ and Pbx1+.

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 13

FEATURE

Broad and Important Implications of a

Rare Kidney Disease

By Erika Opingari

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ith a growing list of diseases and conditions ailing humankind today, it is understandable that the most prevalent ones take precedence in our minds and in our healthcare systems.

While rare diseases, also known as orphan diseases, have much lower incidence rates, they may also have a lower standard of medical care supporting patients and families afflicted by them. When it comes to research, rare diseases are untapped ground, presenting a rewarding opportunity for scientists and clinicians to make discoveries that have a profound impact on patient outcomes.

Trained in Germany, Dr. Christoph Licht is an expert nephrologist appointed at The Hospital for Sick Children and Toronto General Hospital, and full professor of paediatrics at the University of Toronto.

Actively involved in clinical and basic science research, Dr. Licht focuses his expertise and efforts on rare complementmediated kidney diseases, namely atypical hemolytic-uremic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN, or today: C3 glomerulopathy, C3G).

Most often caused by a genetic mutation or autoantibodies, aHUS can manifest anytime from childhood to senior life, with an annual incidence estimated to be about two cases per 1,000,000 people.1 The first report of a genetic defect in the complement system was published in 1998, a milestone which opened the doors for patient screening and gathering more data.2 Today, half a dozen mutations and anti-complement factor H (FH) autoantibodies have been identified that result in dysregulation, and more specifically, upregulation of the complement system.

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The complement system is a principle contributor to our innate immunity, which is constantly present and ubiquitously active. All tissues are covered with lowgrade active complement proteins that serve to identify and distinguish self from non-self-tissue. As Dr. Licht passionately describes, “It’s great biology, it’s ancient biology, which means it’s powerful biology.”

The microvasculature of the kidneys is particularly susceptible to complementmediated thrombotic microangiopathy.

Essentially, overactivation of the complement system causes endothelial damage and clot formation, leading to kidney failure and—in extreme cases— even death.

By manipulating endothelial cells to mimic the inside of a blood vessel, Dr. Licht’s lab aims to identify what occurs to tissues attacked by the complement system, with a recent focus on changes in energy consumption and mitochondrial function.

Historically, the teaching has been that once the complement system is activated, cells die, and the dead cell surface is the starting point for inflammation and coagulation. The truth however is likely more complex. Once activated on the cell surface, complement proteins form membrane attack complexes which create pores in the cell’s membrane. Dr. Licht’s lab has demonstrated that these pores result in a rapid and massive influx of calcium into the cells, which consequently impairs mitochondrial function and reduces adenosine triphosphate (ATP) reservoirs (the main energy currency of cells). In response, cells go into a state of hibernation, during which they use minimal energy and activate replacement mechanisms like autophagy (cellular degradation) and mitophagy

(mitochondrial degradation), as has been demonstrated by Dr. Licht’s lab.

Dr. Licht’s research indicates that while these cells are severely impacted by the complement attack, they also initiate survival mechanisms such as suspending certain functions like motility in attempts to conserve energy and survive. While being motile allows viable endothelial cells to minimize lesions in the monolayer, it is an energy-demanding process that the cells can no longer afford. Therefore, rather than a dichotomous outcome of life or death, endothelial cells have evasion strategies that allow them to survive a complement attack and avoid apoptosis. What remains unexplored is the extent to which these cells can survive under complement stress.

Dr. Licht aims to answer this question, with projects currently underway.

As a ubiquitous modulating system, the complement system likely has implications in many more contexts than we appreciate today. Looking outside the kidneys, Dr. Licht hypothesizes that complementmediated mitochondrial dysfunction is likely a common mechanism across various tissues, particularly impacting high turnover and energy sensitive tissues such as neuronal, retinal and muscle tissue.

Accordingly, Dr. Licht explains that the field is “in a period of transition from a very finite and limited number of welldefined complement-mediated diseases, to an increasing list of conditions in which the complement system plays a role.”

With a growing spectrum of conditions and broader applicability comes an opportunity for greater impact.

Furthermore, as the understanding of these diseases grows, there is a conceptual

FEATURE transition in how to manipulate and treat complement dysregulation. As Dr. Licht explains: “Smart treatment in the future will include tools to identify where [the complement] plays a role, assess its function and dysfunction, and then define the windows of opportunity for complement-modulating treatment. Rather than shutting down the entire system, the way forward may be modulating one effector arm or a few factors that are key players in some conditions, leaving the rest of the cascade alone.” The significance of this research is not only knowledge development, but it’s also translatability into improved patient outcomes.

The only treatment currently available for aHUS is the monoclonal anti-C5 antibody, eculizumab, a first-in-class drug that inhibits complement activation, thus effectively and safely treating aHUS.3,4 Since its approval in 2011 by the Food and Drug Administration and the European Medical Association, followed in 2013 by Health Canada, eculizumab has singlehandedly transformed the outcomes of patients and the epidemiology of the disease.3 Just a few doses of eculizumab can drastically change the health status of patients, allowing them to lead a normal life with regular treatment and monitoring. However, this treatment comes at a staggering cost of $500,000 to $700,000 per patient per year, making

it one of the most expensive drugs on the market.5 Thirteen years later, the sole company manufacturing this drug, Alexion, continues to hold a monopoly over the market. With their patent protection coming to an end soon, several new companies are emerging with similar drugs, hopefully improving accessibility for patients in the future.

that we must engage in more public conversations and change the concept around orphan diseases and drug development.

“The current system is unsustainable, unaffordable and exclusive to certain groups.

There is a big problem of lack of justice,” says Dr. Licht. He highlights that although drug development is costly, we need to find a way to improve accessibility for patients.

“There’s a major international sense of dissatisfaction, since entire countries are cut off access to this drug—China, India, most of Russia, and Africa. This is a treatment that’s currently available and accessible to First World countries only. And that is just not acceptable” says Dr. Licht.

“Overpriced drugs are prohibitive in terms of what physicians would naturally be doing and creates challenges for the field moving forward” Dr. Licht stated. With limited access to eculizumab, physicians cannot use it in conditions that would likely be responsive, thereby limiting the benefit of treatment and opportunities for learning and discovery. The financial barrier not only affects patients and their families, but the medical decisions of the physicians involved in their care.

The cost of treatment is understandably a major challenge in patient management.

The first time Dr. Licht applied for hospital coverage of treatment for a young patient with aHUS, he was turned down— “the cost of treatment for one patient would be the equivalent of keeping an obesity clinic open. Now we treat one patient and let down many more on the other side.” This exemplifies the problem experienced by health care systems around the world—with limited resources, what is the most ethical and sound choice?

“It also raises a point that there is a general problem regarding orphan diseases and related treatments.” Dr. Licht emphasizes

Research and development in complementmediated diseases clearly has a long way to go. By better understanding the mechanism of disease, we can develop better criteria and tools for detection, monitoring, and treatment of complement-mediated diseases. Although colloquially referred to as orphan diseases, patients and their families are not alone in their medical journey, thanks to the dedication and advocacy of clinicians and scientists, like Dr. Licht, around the world.

References

Photo by Krystal Jacques

DR. CHRISTOPH LICHT MD, FRCP(C), FASN Staff Physician, Division of Nephrology, The Hospital for Sick Children and Division of Nephrology, Toronto General Hospital Director, Dialysis and Apheresis Program Senior Scientist, Cell Biology Program, Peter Gilgan Centre for Research and Learning Professor, Department of Paediatrics, University of Toronto

1. Constantinescu AR, Bitzan M, Weiss LS, Christen E, Kaplan BS, Cnaan A, et al. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis. 2004 Jun;43(6):976–82.

2. Warwicker P, Goodship TH, Donne RL, Pirson Y, Nicholls A, Ward RM, et al. Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int. 1998 Apr;53(4):836–44.

3. FDA Approves Conversion of Soliris® (eculizumab) Accelerated Approval in aHUS to Regular Approval for the Treatment of Patients with aHUS | Alexion Pharmaceuticals, Inc [Internet]. [cited 2019 Dec 6]. Available from: https://news.alexion. com/press-release/product-news/fda-approves-conversionsoliris%C2%A0eculizumab-accelerated-approval-ahus-regu 4. Licht C, Greenbaum LA, Muus P, Babu S, Bedrosian CL, Cohen DJ, et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int. 2015 May;87(5):1061–73.

5. The Lancet Haematology. The rising cost of orphan drugs. The Lancet Haematology. 2015 Nov 1;2(11):e456.

6. Crowe K. How a pharmaceutical firm priced its life-saving drug at $500K a year | CBC News [Internet]. CBC. 2015. Available from: https://www.cbc.ca/news/health/how-pharmaceuticalcompany-alexion-set-the-price-of-the-world-s-most-expensivedrug-1.3125251 7. World’s most expensive drug — which costs up to $700,000 per year — too expensive, Canada says | National Post [Internet]. Available from: https://nationalpost.com/health/worlds-most-expensivedrug-prescription-that-costs-up-to-700000-per-year-too-expensivecanada-says

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 15

FEATURE

Tackling Inflammation and Equity

By Diana Hamdan

D

id you know that a person with kidney disease can lose more than 50% of their kidney function before any symptoms appear? One in ten Canadians lives with kidney disease1, an almost 35% increase since 2008.2 Patients with end-stage kidney disease are either treated with dialysis, or if deemed eligible, receive a kidney transplant. Following an initial series of tests, individuals are placed on a waiting list and may wait several years before receiving a transplant, depending on the availability and compatibility of donor kidneys. Kidney transplantation is further complicated by ischemiareperfusion injury (IRI), an inevitable consequence of organ transplantation. IRI is characterized by restricted blood supply to the organ followed by the restoration of blood flow and re-oxygenation. Renal IRI can trigger inflammatory molecular cascades, which puts the recipient at risk of developing acute kidney injury (AKI), ultimately leading to kidney failure.

“Despite our knowledge of the detailed biology of kidney disease, we have limited tools that effectively inhibit the progression of kidney disease, and the treatments available are mainly supportive,” says Paediatric Nephrologist and Senior Scientist, Dr. Lisa Robinson.

Clinical interventions that mitigate organ injury as well as signaling molecules involved in the migration of immune cells during inflammation have been the focus of her research over the last two decades.

Dr. Lisa Robinson is a University of Toronto Professor in the Department of Paediatrics, Head of the Division of Nephrology at the Hospital for Sick Children (SickKids), and a Senior 16 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

Scientist in the Cell Biology program at the SickKids Research Institute. She received her undergraduate and medical degrees at the University of Toronto. She completed an internal medicine internship at the Toronto General Hospital (TGH) followed by a Paediatrics residency at the University of Western Ontario. Following her residency, she held a fellowship in paediatric nephrology at Duke University in North Carolina, where she completed her research training in the Departments of Immunology and Medicine, as a part of the Pediatric Scientist Development Program. In 1991, she held a junior faculty position at the Duke University Medical Center before returning to Toronto in 2002, joining SickKids as a Nephrologist and Scientist.

Dr. Robinson’s primary research interests lie in inflammation in the context of acute kidney injury, kidney fibrosis, and atherosclerosis. One specific area of her research is aimed at understanding mechanisms that regulate immune cell trafficking to inflamed tissue. Her work and others have shown that a blood vessel wall protein, known as fractalkine, is highly expressed in inflamed tissues and plays a key role in transplant rejection and atherogenesis.3,4 Despite its wide involvement in inflammatory disease, little is known about the molecular mechanisms regulating the expression and activity of fractalkine. The Robinson Lab is actively studying molecular players and signaling pathways involved in the production of fractalkine.

Another aspect of Dr. Robinson’s research harnesses endogenous signaling cues that our bodies normally use to limit excessive inflammation as novel therapeutics for

renal and vascular injury. The highly conserved, secreted Slit proteins and their Robo receptors were initially characterized as neuronal migration repellents in the developing nervous system of Drosophila melanogaster (fruit flies). Recent reports have pointed to the role of Slit and Robo outside of development, particularly in inflammation. Dr. Robinson’s team found that a specific isoform of the Slit protein group, known as Slit2, inhibits migration of multiple subsets of white blood cells towards inflammatory mediators by binding to cell surface receptor, Robo-1.5-7 Using a mouse model of induced renal IRI, they also showed that exogenous administration of Slit2 markedly reduced acute kidney injury and curbed collagen deposition and fibrosis.7 Additionally,

Photo by Avideh Gharehgazlou

Lisa Robinson, MD, FRCPC Professor, Department of Paediatrics, Faculty of Medicine Division Head of Nephrology, The Hospital for Sick Children (SickKids) Senior Scientist, SickKids Research Institute Associate Dean, Inclusion and Diversity, Faculty of Medicine

FEATURE

Photo by Avideh Gharehgazlou

Slit2 has been shown to act as a potent anti-platelet agent in vivo and in vitro, an invention Dr. Robinson patented.8 “This is super exciting because Slit2 is naturally produced in the human body, making it a promising therapeutic tool in the clinic.”

Currently, Dr. Robinson and her team are working on determining the smallest portion of Slit2 required to exert its antiinflammatory functions.

As for her translational research, Dr. Robinson, in collaboration with Transplant Surgeon Scientist Dr. Markus Selzner at the University Health Network (UHN), has pioneered normothermic ex vivo kidney perfusion (NEVKP) as a novel approach for renal graft preservation.

Normothermic perfusion is a method of maintaining organ viability at physiologic temperatures (35-38°C), as opposed to the cold temperatures traditionally used in hypothermic perfusion (0-8°C). In a pig transplantation model, NEVKP was shown to minimize renal IRI damage and improve graft functional recovery compared to cold storage.9, 10 In late 2017, NEVKP was successfully used on a human kidney graft at TGH. Beyond her research interests, Dr. Robinson is an advocate for diversity and equitable access to science. Children in low-income neighbourhoods of Ontario have consistently scored lower in the compulsory grade ten literacy test compared to their more affluent counterparts. This has been linked to elevated levels of high school incompletion, lower post-secondary

matriculation, poorer health outcomes and a decreased level of wellbeing.11 Given the gravity of the disparity that exists in Ontario, Dr. Robinson founded the Manulife Kids Science & Technology program at SickKids in 2006, which provides at-risk middle and high school students in disadvantaged neighbourhoods with an equitable access to interactive science opportunities.

The program has reached over 20,000 students across Ontario by the spring of 2018. Additionally, Dr. Robinson also founded the Student Advancement Research (StAR) program at SickKids, which provides under-represented minority high school students with a six-week paid summer internship in research and clinical shadowing. Through these programs, Dr. Robinson hopes to broaden the youths’ perspective on Science, Technology, Engineering and Mathematics (STEM), and encourage them to attain higher education and employment in the STEM field.

In 2016, Dr. Robinson was appointed the Chief of Diversity Officer, the first position of its kind in a Canadian medical school. “There was a growing recognition of the disparities in diversity between the Faculty of Medicine’s demographic and that of our multicultural Toronto community”, she explains. She helped establish the Diversity Advisory Council, which involves members across the Faculty of Medicine as well as external partners, such as the Toronto Academic Health Sciences Network (TAHSN), who share strategies to identify and break down the

barriers to inclusion and diversity. As a clinician scientist, Dr. Robinson believes in the importance of gathering data to drive our knowledge of the instances and patterns of discrimination, harassment and exclusion. By conducting surveys aimed at all members in the Faculty of Medicine, including medical students and residents, post-docs, graduate students, faculty and other staff members, the Office of Inclusion and Diversity is working on designing programs and policies that promote an inclusive learning and working environment. With her new title as Associate of Inclusion and Diversity, Dr. Robinson continues to promote equity, inclusion and diversity in admissions, education, and recruitment at the University of Toronto Faculty of Medicine.

“If we truly strive for excellence in training our future care providers and scientists, we have to embrace inclusivity.”

References

1. Manns B, McKenzie SQ, Au F, Gignac PM, Geller LI, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) Network. The financial impact of advanced kidney disease on Canada Pension Plan and private disability insurance costs. Canadian journal of kidney health and disease. 2017 Apr 13;4:2054358117703986.

2. Organ replacement in Canada: CORR annual statistics, 2018, https://www.cihi.ca/en/organ-replacement-in-canada-corr-annualstatistics-2018, supplemented with data collected by the Quebec Branch of The Kidney Foundation of Canada as provided by renal units. *Excludes Québec.

3. Robinson LA, Nataraj C, Thomas DW, Howell DN, Griffiths R, Bautch V, Patel DD, Feng L, Coffman TM. A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection. The Journal of Immunology. 2000 Dec 1;165(11):6067-72.

4. Fong AM, Robinson LA, Steeber DA, Tedder TF, Yoshie O, Imai T, Patel DD. Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. Journal of Experimental Medicine. 1998 Oct 19;188(8):1413-9.

5. Tole S, Mukovozov IM, Huang YW, Magalhaes MA, Yan M, Crow MR, Liu GY, Sun CX, Durocher Y, Glogauer M, Robinson LA. The axonal repellent, Slit2, inhibits directional migration of circulating neutrophils. Journal of leukocyte biology. 2009 Dec;86(6):1403-15.

6. Mukovozov I, Huang YW, Zhang Q, Liu GY, Siu A, Sokolskyy Y, Patel S, Hyduk SJ, Kutryk MJ, Cybulsky MI, Robinson LA. The neurorepellent slit2 inhibits postadhesion stabilization of monocytes tethered to vascular endothelial cells. The Journal of Immunology. 2015 Oct 1;195(7):3334-44.

7. Chaturvedi S, Yuen DA, Bajwa A, Huang YW, Sokollik C, Huang L, Lam GY, Tole S, Liu GY, Pan J, Chan L. Slit2 prevents neutrophil recruitment and renal ischemia-reperfusion injury. Journal of the American Society of Nephrology. 2013 Aug 1;24(8):1274-87.

8. Patel S, Huang YW, Reheman A, Pluthero FG, Chaturvedi S, Mukovozov IM, Tole S, Liu GY, Li L, Durocher Y, Ni H. The cell motility modulator Slit2 is a potent inhibitor of platelet function.

Circulation. 2012 Sep 11;126(11):1385-95.

9. Kaths JM, Echeverri J, Goldaracena N, Louis KS, Chun YM, Linares I, Wiebe A, Foltys DB, Yip PM, John R, Mucsi I. Eighthour continuous normothermic ex vivo kidney perfusion is a safe preservation technique for kidney transplantation: a new opportunity for the storage, assessment, and repair of kidney grafts.

Transplantation. 2016 Sep 1;100(9):1862-70.

10. Kaths JM, Hamar M, Echeverri J, Linares I, Urbanellis P, Cen JY, Ganesh S, Dingwell LS, Yip P, John R, Bagli D. Normothermic ex vivo kidney perfusion for graft quality assessment prior to transplantation. American Journal of Transplantation. 2018 Mar;18(3):580-9.

11. Alexander C, Bendiner J. Canada’s Literacy and Numeracy Challenge Worsens. TD Economics; 2013.

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 17

BMC FEATURE

Master of Science in

BIOMEDICAL COMMUNICATIONS Evelyn Lockhart

Graduating year: 2T0

Evelyn Lockhart is a pathologist and transfusion medicine physician currently completing her Master of Science in Biomedical Communication (MScBMC) at the University of Toronto. Evelyn earned her MD in 2001 from the University of North Carolina at Chapel Hill. Previously, she was the medical director of the Carolinas Region American Red Cross, associate medical director of transfusion at Duke University Hospital, and medical director of transfusion at the University of New Mexico Hospital. She is currently a Clinical Associate Professor of Pathology at the University of New Mexico Health Science Center. evelynlockhart.com

18 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

BMC FEATURE

BRITTANY CHEUNG

Graduating year: 2T1

I studied at the University of Toronto, where I majored in biology and psychology and took a special interest in animal diversity and evolution. During that time, I reconstructed the ancient invertebrate Amiskwia sagittiformis, a task that finally allowed me to combine my two great passions, art and biology. Seeing how much I enjoyed the project, my supervisor introduced me to the BMC program, and I knew immediately it was the program for me. I look forward to learning from my inspiring peers and teachers so I can better participate in a field that is my childhood dream come true.

katrina Hass

Graduating year: 2T1

My name is Katrina Hass and I’m a first year BMC student. I’m from a small mining town in Northern Ontario where the population is less than the population of U of T. As an undergraduate student, I studied Health Sciences at McMaster University. I would often seek out projects that allowed me to use my passion for art. I realized throughout my studies that I loved using art as a medium to promote an understanding of the sciences. I am thrilled to be able to fulfill my dream of becoming a medical illustrator and to be surrounded by such inspiring faculty and classmates. Instagram: artby.katrina

JENNIFER BAROLET

Graduating year: 2T1

My interest in illustration and graphic design started at an early age.

I always had a passion for art, however an interest in chemistry and mathematics led me to study engineering at the University of Toronto.

Most recently I have combined my career experience in science and technology with formal fine art academic training at the Academy of Realist Art in Toronto to successfully produce precise, detailed and accurate realistic visual art. Complimenting this with the graphic design and illustration skills learned at OCAD U reinforced my desire to explore avenues to design and develop visual media to advance the learning experience for those interested in science.

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 19

VIEWPOINT

Surface versus Structure: The longstanding issue of the gender pay gap in medicine

By Krystal Jacques

T

he issue of the gender pay gap is frequently forgotten by today’s society but is still pervasive across various fields of work today. A 2019 report

by StatsCan revealed that Canadian women earn 0.87 cents for every dollar earned by men.1 And the gap starts early, according to a new report that tracked the earnings of Canadian post-secondary graduates across 11 fields of study (including college, bachelors, masters, and doctoral degrees).

Women earned less than men in every field, with an average gap of $5,700 (12% less than men) in the 1st year after graduation, which increased to $17,000 (25% less than men) after 5 years.2 Ontario’s gender pay gap has narrowed significantly since 1987 when the provincial government first passed the Pay Equity Act. But according to a 2019 report

by Glassdoor, it will take 164 years to close the gender wage gap in Canada.3 At present , jobs that mirror traditional “women’s work” (e.g. administrative, early childhood educators) tend to be undervalued because they parallel domestic work

20 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

that women were (and are) expected to perform for free. Whether the gender pay gap exists in higher paying careers, such as medicine, is a contentious issue. According to a 2020 U.S. report, a pay gap between male and female physicians at the outset of their careers not only exists, but is actually growing.4 The starting salaries of female doctors were on average $36, 618 lower than male doctors from 1999 to 2017.4 Here, we will discuss the possible reasons for the gender pay gap in medicine-a field historically dominated by men that continues to be plagued by in-built institutional gender bias.

A recently published study in JAMA Neurosurgery analyzed 1.5 million surgical procedures from the start of 2014 through 2016; it found female surgeons in Ontario earn 24% less than their male counterparts, and the proportion of women performing an operation decreased as the pay per hour for that procedure increased.5 A similar article by the Association of American Medical Colleges (AAMC) summarizing gender-based pay disparities in medicine from several resources in the Unities States (U.S.) was published a few months earlier.

These articles bring into awareness the many possible reasons for why this gender pay gap is occurring: 1) women tend to have less aggressive billing behaviours than men, 2) men tend to refuse the less lucrative medical procedures, while women tend to say yes to any opportunity they can get, 3) female physicians tend not to self-promote or negotiate salary, and 4) women tend to choose the lower paying, less lucrative specialties after their training (i.e. Gynecology).5,6 Out of all female surgeons in Ontario included in the analysis, 49% of them practiced gynecology.7 In the U.S., the percentage of female surgeons working in gynecology versus the more lucrative urology is 54% and 8% respectively.6 According to AAMC specialty data, 63% of pediatricians in the U.S. are women, whereas 95% of orthopedic surgeons are men.

Also, the majority of neurosurgeons are men.5 On the surface, women tend to be less aggressive than men when it comes to self-promotion, negotiation for higher salary, getting the biggest bang for their hours, and choosing the highest paying specialties.

VIEWPOINT

“female

surgeons in Ontario earn 24% less than their male counterparts, and the proportion of women performing an operation decreased as the pay per hour for that procedure increased.

”

However, the 2020 study showing a gender gap in starting salaries for physicians found that work-life balance preferences (eg. predictable hours, length of the workday, frequency of being on-call overnight or on weekends) accounted for less than 1 percent of the pay gap, and had no effect on the differences in starting salary.4 Why are men paid more than women out of the gate? The authors say differences in specialty and the number of job offers received may explain some, but not all, of the gap.

RVU differences reflect a male-dominated structure in medicine, contending that, “The committee that establishes RVUs has 30 voting members. Only two are female.”5 Similarly, the Ontario study found that female surgeons receive fewer referrals overall.7 The reason behind this is suspected to be implicit bias.9 The authors of the Ontario study told the Globe and Mail that a possible solution to this is to pool all the referrals for each specialty and distribute them in an unbiased system.6

Some believe the gender-pay gap is attributable to a difference in skill-that male surgeons are just “more capable”. However, the recent Ontario study found that in almost all cases, female and male surgeons took the same amount of time to perform identical procedures, debunking the myth that females are just “less competent” or that they work less efficiently than men.

Although it may be the case that women value flexibility over lucrativeness when pursuing medicine (due to the increased demands of domestic, child and elder-care socially expected from women), the gaps also persist within speciality. Particularly in male dominated specialties. In a paper published in 2017, researchers compared Relative Value Unites (RVUs – a system of work compensation implemented primarily

by U.S. medicare) between gynecologic and urologic procedures performed in the U.S. They found that 84% of procedures were compensated at a higher rate for male-specific procedures. For example, a biopsy of the prostate is worth 4.61 RVUs while a biopsy of the endometrium is 1.53 RVUs.8

Besides the inherent male-bias in the structure of the medical system, research and personal experiences would suggest that differences in ambition and assertiveness is a reflection of a cultural and societal artifact.

It is well documented that in childhood, girls are typically taught to be less aggressive and less confident, while boys are taught the opposite.10,11 And what seems like incompetence in female surgeons could just be lack of confidence. So how can we address this gender-pay disparity in medicine?

Even more nefarious is the fact that the same procedure-a total urethrectomy-has different RVUs depending on whether it is performed on a man or a woman. For men, it is 16.85; for women, 13.72. Although we cannot completely rule out the possibility that the procedure is inherently more difficult when performed on men than on women (research on this is limited), Parangi, an MD at Harvard Medical School, and the main interviewee of the AAMC article, suspects that the real reason for these

First, we must address institutional bias by ensuring the real-world gender ratio of medical practitioners is reflected in the governing bodies and committees who make decisions. Another solution could be putting systems into place making it impossible for surgeons to refuse lower paying procedures.

But it also means we must teach all children, regardless of gender, to be confident in their skills and capabilities. Many women choose to reduce their hours to start a family, however new fathers are less likely to do so.

Fathers should also be encouraged by society to share the responsibilities of childcare equitably with their partner. Perhaps this would allow women to reduce their hours by a little less or return to work more quickly after maternal leave.

Last, it is important not to forget that there are many in our world that perceive women as lazy or incompetent. We see the term “lazy” also used to describe disparities in work compensation between races. Women of colour, Indigenous women, and women

with disabilities are even more worse off than white woman when it comes to the gender pay gap overall.12 For example, in the U.S, black male doctors make an average of $50,000 less per annum than white male doctors, while black female doctors make almost $100,000 less than black male doctors.13 It is pivotal that we also study the intersections between race and gender to address the gender pay gap issue more thoroughly and implement solutions that ensure all women are paid fairly.

References

1. Accenture. Accenture Study Finds Growing Demand for Digital Health Services Revolutionizing Delivery Models: Patients, Do [Internet]. Newsroom. Accenture; 2018 [cited 2019Nov7]. Available from: https://newsroom.accenture.com/news/accenture-studyfinds-growing-demand-for-digital-health-services-revolutionizingdelivery-models-patients-doctors-machines.htm.

2. Perez S. IDC: Apple led wearables market in 2018, with 46.2M of the total 172.2M devices shipped [Internet]. TechCrunch.

TechCrunch; 2019 [cited 2019Nov7]. Available from: https:// techcrunch.com/2019/03/05/idc-apple-led-wearables-market-in2018-with-46-2m-of-the-total-172-2m-devices-shipped/.

3. Apple. Apple announces three groundbreaking health studies [Internet]. Apple Newsroom. 2019 [cited 2019Nov7]. Available from: https://www.apple.com/ca/newsroom/2019/09/appleannounces-three-groundbreaking-health-studies/ 4. Fitbit. Fitbit to Be Acquired by Google [Internet]. Press Release Details. 2019 [cited 2019 Nov7]. Available from: https://investor.

Fitbit.com/press/press-releases/default.aspx 5. Cyrcadia Health. Core Technology [Internet]. Cyrcadia Health. [cited 2019Nov7]. Available from: http://cyrcadiahealth.com/ core-technology/ 6. Microsoft. Project Emma [Internet]. Microsoft Research. 2017 [cited 2019Nov7]. Available from: https://www.microsoft.com/ en-us/research/project/project-emma/ 7. Philips. Wireless Wearable Biosensor for Vital Signs Monitoring: Philips Healthcare [Internet]. Philips. [cited 2019Nov7]. Available from: https://www.usa.philips.com/healthcare/clinical-solutions/ early-warning-scoring/wireless-biosensor 8. Tran V-T, Riveros C, Ravaud P. Patients’ views of wearable devices and AI in healthcare: findings from the ComPaRe e-cohort. npj Digital Medicine [Internet]. 2019Jun14;2(1). Available from: https:// www.nature.com/articles/s41746-019-0132-y 9. Izmailova ES, Wagner JA, Perakslis ED. Wearable Devices in Clinical Trials: Hype and Hypothesis. Clinical Pharmacology & Therapeutics [Internet]. 2018Apr2;104(1):42–52. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032822/ 10. Center for Devices and Radiological Health. Consumers (Medical Devices) [Internet]. U.S. Food and Drug Administration.

FDA; [cited 2019Nov25]. Available from: https://www.fda.gov/ medical-devices/resources-you-medical-devices/consumersmedical-devices#What_is_the_difference_between_Cleared_and_ Approved_ 11. PricewaterhouseCoopers. PwC Canada’s Consumer insights survey: The experience is pertinent to Canadian consumers [Internet].

PwC. 2019 [cited 2019Nov25]. Available from: https://www.pwc. com/ca/en/media/release/canada-consumer-insights-survey.html 12. Canada H. Government of Canada [Internet]. Canada.ca.

Government of Canada; 2018 [cited 2019Nov25]. Available from: https://www.canada.ca/en/health-canada/services/drugs-healthproducts/medical-devices/activities/announcements/notice-digitalhealth-technologies.html 13. Bowling A. Mode of questionnaire administration can have serious effects on data quality. Journal of Public Health.

2005May3;27(3):281–91.

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 21

VIEWPOINT

By Mashal Ahmed

C

annabidiol! The new magic elixir, the miracle drug, cure to every possible ailment you can think of. Whether you suffer from depression, anxiety, psychosis, epilepsy, arthritis, migraines, dry skin, insomnia, an opiate addiction or the unrelenting pain from high heels – this wonder drug can heal all, adherents claim. Over the past two years cannabidiol products have exploded into mainstream markets, with certain health enthusiasts and social media influencers treating the compound as the new “cure-all”.

Cannabidiol, or CBD, is a major cannabinoid constituent of Cannabis plants. However, unlike THC (tetrahydrocannabinol)—the primary psychoactive compound in many cannabis products—CBD does not produce any psychoactive or mind-altering symptoms.1 Whereas THC often induces anxiety and psychosis-like effects, CBD tends to reverse them. In fact, research suggests that CBD has the potential for multiple beneficial health improvements, including neuroprotective, anti-inflammatory, antiepileptic, antianxiety and antipsychotic effects.1 In 2018, the high-profile case of Billy Caldwell drew CBD into the media spotlight. Thirteen-year old Caldwell of Northern Ireland suffers from treatmentresistant epilepsy and relies on a CBD-based medication to control his seizures. He made 22 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

headlines last year when his imported medication was confiscated at a London airport; medicinal cannabis was illegal in the UK at the time. This case resulted in a fierce public debate on medicinal cannabis use and its health benefits.2 In November 2018, prescribed medicinal cannabis was finally legalized in the UK for patients with exceptional clinical needs. Caldwell’s medicine, Epidolex, is a purified CBD extract made specifically to treat individuals with severe forms of epilepsy. Two recent clinical trials showed that epileptic patients treated with Epidolex had significantly greater reduction in the frequency of atonic seizures compared to patients treated with placebo.3,⁴ CBD has also become a major drug of interest in the field of mental health,

that patients treated with CBD showed significant improvement in psychotic symptoms compared to those treated with placebo. The CBD-treated group also demonstrated a trend for cognitive improvement, with no major side effects from the drug.⁵ In an interview with The Guardian he called CBD “the hottest new medicine in mental health”. Although optimistic, Dr. McGuire is still cautious about the current findings, noting that larger scale and longer-term clinical trials are needed before CBD can be introduced as a formal antipsychotic.

Despite the need for further clinical investigation, CBD products have exploded beyond the clinical realm into the larger over-the-counter marketspace in the past two years. “CBD” and “hemp-based” have

...company and consumer claims all lack one important detail: empirical evidence. with studies suggesting mild to moderate improvements in anxiety and psychotic disorders.1 Dr. Philip McGuire, professor of psychiatry at King’s College London, has been studying CBD for over 15 years. His recent clinical trial investigated the effects of CBD on patients with schizophrenia.⁵ Results of this randomized, placebocontrolled, double-blinded study showed

become buzzwords, especially amongst upscale beauty brands. Product sales are now projected to reach $22 billion USD by 2022.⁷ This projected growth is largely due to CBD’s status as a health and wellness product; a quality highly desired by the growing body of health-conscious modern-day consumers looking for the “organic” option.

VIEWPOINT Latching on to shifting consumer trends, hemp-based health boutiques are popping up everywhere, offering a line-up of oils, lotions, and pastes to please the CBD craze. Danielle Blair, owner of Torontobased Calyx Wellness, offers an array of CBD products in addition to other holistic remedies such as crystal healing and reiki. Her business aims to create open, informative dialogue about CBD therapies and make such natural remedies more accessible in the Canadian health and wellness market.8 However, the CBD frenzy has expanded beyond small businesses to the mainstream market. You can now find CBD-infused into just about anything. Products range from CBD soaps, toothpastes, and chewing-gum to truffles, spring water, alcoholic beverages, and even CBD-infused pillowcases. While some companies claim their products provide a sense of calmness, others say their products help individuals become more focused and grounded.

The CBD hype only continues to grow; however, company and consumer claims all lack one important detail: empirical evidence. Since CBD is marketed as a nutraceutical rather than a pharmaceutical product, it is not subject to regulated randomized-controlled clinical trials.

Without such assessments there is no way to determine whether the effects of such products are due to CBD or placebo. In his interview with The Guardian, Dr. McGuire also notes that during the psychosis and epilepsy trials, patients were given about 1,000 to 2,000 mg of pure CBD tablets each day for a certain number of weeks.6 In comparison, a single CBD-infused coffee or pastry may only contain 5 mg of the compound. Thus, individuals must also consider how much of that compound is actually metabolized by their body. “Of that 5 mg, you might absorb 1 mg or less”, says Dr. McGuire. “A lot of what people may be taking in good faith may [have] absolutely no effect at all, other than a placebo effect”.6

Big name celebrities like Kim Kardashian West have also hopped on the bandwagon.

West regularly endorses CBD products through her social media platforms, showing off her CBD-themed parties and meditation sessions to her 150 million+ followers. In a recent interview with People, she talked about how CBD helps her stay relaxed and focused and how her use of CBD gummies has helped regulate her sleep.⁹ Businesswoman and lifestyle expert Martha Stewart has also become a strong CBD advocate. In March 2019, she announced her new partnership with Canopy Growth, through which she aims to produce a new line of CBD lifestyle products for consumers and their pets.10

Another concern with the current trend is that consumers may try an advertised CBD product and find that it does not have any effect. Or perhaps they experience side-effects from other ingredients in the mixture. Dr. McGuire worries this confusion may lead consumers to believe that CBD has no health benefits at all. In the long-run, these misconceptions could “damage the therapeutic potential of what could be a very useful new medicine”, Dr. McGuire explains.6

Photo: iStock

So, what is the bottom line? Clinical trials assessing the treatment potential of CBD show promising results in the area of neurological disorders and mental illness,

although further investigation is warranted for more conclusive evidence. However, the expansion of CBD into mainstream markets has given rise to products with unreliable and unmeasured health effects. Moreover, viral marketing fueled by health enthusiasts and social media support has propagated exaggerated and sometimes false claims about the effects of CBD-based products.

Thus, many ill-informed consumers may be indulging in products that produce little to no health benefits at all. Overall, conflicting consumer experiences may serve to damage the therapeutic potential of CBD, which is still being clinically investigated.

In order to mitigate the spread of false information and provide consumers with a more educated background on their product purchases, the CBD market requires urgent regulation. Setting standards for CBD product purity and dosing would help ensure safety and efficacy, clarify associated risks and benefits, and streamline processes for labelling and marketing. Most importantly, CBD regulation would allow us to hold companies accountable for the promises they make to their consumers.

References 1. Mandolini GM, Lazzaretti M, Pigoni A, et al. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. Epidemiology and psychiatric sciences. 2018 Aug;27(4):327-35.

2. Busby M. Billy Caldwell licensed for cannabis oil use in Northern Ireland. The Guardian [Interenet]. 2018 [cited 2019 Nov 3]. Available from: https://www.theguardian.com/society/2018/jul/05/billy-caldwe ll-heads-home-amid-doubts-over-cannabis-oil-access-northern-irleand-medication-epilepsy 3. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. New England Journal of Medicine. 2017 May 25;376(21):2011-20.

4. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox Gastaut syndrome. New England Journal of Medicine. 2018 May 17;378(20):1888-97.

5. McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. American Journal of Psychiatry. 2017 Dec 15;175(3):225-31.

6. Lewis T. CBD: a marijuana miracle or just another health fad?. The Guardian [Internet]. 2019 [cited 2019 Nov 3]. Available from: https://www.theguardian.com/society/2019/may/05/cbd-a-marijuana-miracle-or-another-health-fad-cannabidiol-anxiety-epilepsy 7. CBD worth $22 billion by 2022? That’s crazy, right? [Internet]. Brightfield Group. 2018 [cited 2019 Nov 3]. Available from: https://www. brightfieldgroup.com/post/cbd-worth-22-billion-by-2022 8. Scriver A. Meet Danielle Blair of Canada’s First CBD Boutique Calyx Wellness. Edit Seven [Internet]. 2018 [cited 2019 Nov 3]. Available from: https://editseven.ca/danielle-blair-canada-cbd-boutique-calyx-wellness/ 9. Frey K. Kim Kardashian Uses CBD to Help Her Fall Asleep, Says She Wouldn’t Take ‘Xanax or Ambien Again’. People [Internet]. 2019 [cited 2019 Nov 3]. Available from: https://people.com/style/kim-kardashian-uses-cbd-for-sleep/ 10. Owram K. Martha Stewart Developing Cannabis Pet Care, Cosmetics and Food. Bloomberg [Internet]. 2019 [cited 2019Nov3]. Available from: https://www.bloomberg.com/news/articles/2019-06-18/martha-stewart-developing-cannabis-pet-care-cosmetics-and-food

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 23

VIEWPOINT

By Serina Cheung

W

hile the 2010s will be known as the rise of the smartphone, the 2020s are poised as the rise of “wearables”. Electronic devices that consumers can wear, such as smartwatches, are considered “wearable technology”. The advancement of smartphones has allowed for technology to be intricately woven into many aspects of our daily lives. From asking Siri the weather to tracking our steps, mobile technology is a powerful tool to make everyday tasks easier. In recent years, wearable technology has found its place in society with a particular focus on health and fitness. Consumers are becoming increasingly health conscious with the desire to take ownership of their health. According to Accenture, the use of wearable technology in the U.S. jumped from 9% in 2014 to 33% in 2019.1 As the popularity of wearables surge, the 2020s look promising for the rise of wearable technology.

The first wearable technology to achieve mainstream success was the Fitbit, a simple wristband to track one’s steps throughout the day. Fitness smartwatches have now evolved into multi-functional 24 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

tools that can track heart rate and detect falls. As of 2018, Apple leads the wearables market with the Apple Watch.2 In the age of big data, the Apple Watch allows an unprecedented amount of data to be collected in real time in an accurate and non-invasive manner. Apple has partnered with top academic medical institutions to launch studies relating to women’s, cardiovascular, and hearing health.3 This innovative approach to data collection allows research institutions to take advantage of the prevalent use of wearables. With each iteration of the Apple Watch becoming more and more health and fitness focused, Apple is inevitably tapping into the vast market for wearables.

The massive success of the Apple Watch has not gone unnoticed, as Google recently acquired Fitbit as their venture into the wearables market.4 Smartwatches dominate the wearables market, however, there has also been an emergence of experimental health-focused wearables with promising applications: ▶The Cyrcadia Breast Monitor is a “smartpatch” for the breast that uses

digital temperature sensors to detect abnormal circadian temperature patterns in breast tissue. This data is submitted to healthcare providers to detect early signs of breast cancer.5 ▶Microsoft developed the Emma Watch, which uses small motors producing rhythmic vibrations to compensate for hand tremors. This technology is beneficial to those suffering from movement disorders such as Parkinson’s disease.6 ▶The Philips wearable biosensor is a medical-grade device that discretely and wirelessly fits on the patient’s chest. It monitors key vital signs such as heart rate and respiratory rate, allowing physicians to continuously monitor patients’ health and be notified when intervention is needed.7 As new wearable technology makes accurate real-time monitoring and data collection easier, several promising applications for the future of the healthcare industry emerge. The remote collection of large amounts of health data allows for the establishment of patterns to train machine learning models. Wearables

VIEWPOINT may have the ability to predict potential health problems before they fully manifest, allowing for early physician intervention and preventative measures. One of the most attractive features of wearables is the ability to collect physiological data in real time. The current routine of patients having their vitals taken at the doctor’s office represents a very narrow snapshot of a person’s physiology. Inferences can be made retroactively if these snapshots of a patient’s vitals are taken every few weeks, months, or years. However, frequent measurements may burden the healthcare system. Accurate and real-time measurements supplied by wearables produces denser datasets allowing for improved understanding of disease variability as well as characterisation of intra- and interpatient variability.

Real-time collection of data is also very useful for clinical and drug development trials. Most trials require patients to complete questionnaires at physical locations. However, if patients could electronically complete questionnaires using their wearables, this would improve compliance and timely collection of data, as well as reducing administrative burden.9 However, it is important to note that different modes of questionnaire administration, such as telephone-based, electronic, or paper-based self-report, introduces biases in the responses. Some of these biases include recall bias and social desirability bias and can have important implications for the validity of results.13 Physiological data collected during early stage clinical trials may identify early safety concerns allowing dosing adjustments to be quickly made.

Towards the end of clinical development, several self-reported measures are made to identify adverse effects. Perhaps wearables could provide objective biomarker measurements of traditionally subjective, self-reported attributes such as pain, fatigue, and nausea.

Although the promising applications of medical-grade wearable devices in the healthcare system have garnered lots of attention, many challenges present themselves before wide mainstream adoption. For example, a recent study in France used wearables to remotely track and analyze patients with chronic conditions in real time. This study

evaluated patients’ perception of the use of wearables and artificial intelligence (AI) in healthcare. Interestingly, only 50% of patients felt that the use of digital tools was beneficial, while 11% considered it a danger. There was distrust in using AI to help physicians predict outcomes and many felt that any decisions should remain a human task.8 Those who work on research and development in the pharmaceutical side may not be familiar with engineering devices. Conversely, the engineers working on the devices may not be familiar with the drug development process. The gap between the two industries may slow the progression of consumer friendly, health wearables. Notable non-medical grade wearables that have reached mainstream adoption include the Apple Watch and Fitbit. However, the Apple Watch is a consumer-grade, as opposed to a medicalgrade wearable. Consumer-grade devices are FDA cleared, as opposed to FDA approved. FDA clearance deems a product to be substantially similar to another marketed device. However, FDA approval requires a more rigorous review. In other words, while the Apple Watch can provide some insight to one’s vitals such as heart rate, it is not meant to replace a trip to the doctor’s office.

The electronic collection of health data also raises concerns of privacy. More than one third of Canadians use health or fitness related applications on their phone, smart watch or tablet.11 Canada is lagging in defining the governance of health data collection by medical devices and consumer-grade wearables.12 However, in the US, consumer-grade and medical devices are under different sets of regulations. Data obtained by medical devices require patient consent for collection and sharing. However, the data obtained by consumer-grade devices such as the Fitbit can be shared in a deidentified manner to third parties.9 Health data is worth billions of dollars to pharmaceutical companies. As such, companies need to attract consumers to consent to data collection to be sold to third parties. Technology companies need to be transparent with the type of data being collected and the option to opt out of third-party access to data. Currently, targeted marketing ads are becoming

increasingly specific and personalized.

Health data is another facet that marketing companies are using to further refine and reach their target audience.

Today, the idea of a smartwatch having the capabilities of a full-scale electrocardiogram is difficult to imagine.

However, as these consumer-grade and medical-grade wearable technologies mature, remote patient monitoring using wearables alone may become a very real possibility. The potential of wearables has inevitably caught the attention of tech giants and pharma companies. With some of the world’s largest companies backing the R&D of wearables, a future of wearables reaching mainstream usage may be even closer than we thought.

References

1. Accenture. Accenture Study Finds Growing Demand for Digital Health Services Revolutionizing Delivery Models: Patients, Do [Internet]. Newsroom. Accenture; 2018 [cited 2019Nov7]. Available from: https://newsroom.accenture.com/news/accenture-studyfinds-growing-demand-for-digital-health-services-revolutionizingdelivery-models-patients-doctors-machines.htm.

2. Perez S. IDC: Apple led wearables market in 2018, with 46.2M of the total 172.2M devices shipped [Internet]. TechCrunch.

TechCrunch; 2019 [cited 2019Nov7]. Available from: https:// techcrunch.com/2019/03/05/idc-apple-led-wearables-market-in2018-with-46-2m-of-the-total-172-2m-devices-shipped/.

3. Apple. Apple announces three groundbreaking health studies [Internet]. Apple Newsroom. 2019 [cited 2019Nov7]. Available from: https://www.apple.com/ca/newsroom/2019/09/appleannounces-three-groundbreaking-health-studies/ 4. Fitbit. Fitbit to Be Acquired by Google [Internet]. Press Release Details. 2019 [cited 2019 Nov7]. Available from: https://investor.

Fitbit.com/press/press-releases/default.aspx 5. Cyrcadia Health. Core Technology [Internet]. Cyrcadia Health. [cited 2019Nov7]. Available from: http://cyrcadiahealth.com/ core-technology/ 6. Microsoft. Project Emma [Internet]. Microsoft Research. 2017 [cited 2019Nov7]. Available from: https://www.microsoft.com/ en-us/research/project/project-emma/ 7. Philips. Wireless Wearable Biosensor for Vital Signs Monitoring: Philips Healthcare [Internet]. Philips. [cited 2019Nov7]. Available from: https://www.usa.philips.com/healthcare/clinical-solutions/ early-warning-scoring/wireless-biosensor 8. Tran V-T, Riveros C, Ravaud P. Patients’ views of wearable devices and AI in healthcare: findings from the ComPaRe e-cohort. npj Digital Medicine [Internet]. 2019Jun14;2(1). Available from: https:// www.nature.com/articles/s41746-019-0132-y 9. Izmailova ES, Wagner JA, Perakslis ED. Wearable Devices in Clinical Trials: Hype and Hypothesis. Clinical Pharmacology & Therapeutics [Internet]. 2018Apr2;104(1):42–52. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032822/ 10. Center for Devices and Radiological Health. Consumers (Medical Devices) [Internet]. U.S. Food and Drug Administration.

FDA; [cited 2019Nov25]. Available from: https://www.fda.gov/ medical-devices/resources-you-medical-devices/consumersmedical-devices#What_is_the_difference_between_Cleared_and_ Approved_ 11. PricewaterhouseCoopers. PwC Canada’s Consumer insights survey: The experience is pertinent to Canadian consumers [Internet].

PwC. 2019 [cited 2019Nov25]. Available from: https://www.pwc. com/ca/en/media/release/canada-consumer-insights-survey.html 12. Canada H. Government of Canada [Internet]. Canada.ca.

Government of Canada; 2018 [cited 2019Nov25]. Available from: https://www.canada.ca/en/health-canada/services/drugs-healthproducts/medical-devices/activities/announcements/notice-digitalhealth-technologies.html 13. Bowling A. Mode of questionnaire administration can have serious effects on data quality. Journal of Public Health.

2005May3;27(3):281–91.

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 25

VIEWPOINT VIEWPOINT

By Jason Lo Hog Tian

M

onosodium glutamate (MSG) is a powerful flavour enhancer that has been a staple in cooking for decades. However, if you have spent any amount of time in a Western country, you are probably aware of the negative reputation of MSG. In fact, many of you may actively avoid MSG after hearing about the negative effects of using the mysterious powder to transform any food from dull to delicious. A deeper dive into the history of MSG reveals that fears are based less in science and more around racialized attitudes that developed after mass immigration to America.

MSG is the salt of glutamic acid, an abundant and naturally occurring amino acid, and was first discovered in 1908 by chemist Ikeda Kikunae in Japan. MSG was isolated from sea kelp-which gives it the signature umami flavour, meaning “tasty” in Japanese. The product was initially brought to market in Japan under the brand name Ajinomoto, meaning “essence of taste”. It quickly spread around the world, ending up in restaurants throughout the United States by the 1930’s and becoming an integral food staple in the American war effort.1 However, following its initial rise to popularity, the flavour enhancer would soon come under fire due to a phenomenon that remains prevalent to this day—consumer fear.

26 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

In the 1960’s, consumer trust in industry products collapsed and fear around the dangers of chemicals such as pesticides, additives, and sweeteners rose to an alltime high. MSG would soon be added to the quickly growing “do not use” list after a letter published in the New England Journal of Medicine in 1968 by Dr. Robert Ho Man Kwok describing what he called “Chinese Restaurant Syndrome” (CRS)

Vintage MSG ad from Ajinomoto kabushiki gaisha shashi [Company History of Ajinomoto Incorporated] (Ajinomoto kabushiki gaisha, 1971), volume 1

after eating at a Chinese restaurant.

Symptoms included numbness in the neck and arms, weakness, and heart palpitations.2 The letter resonated with readers and soon there were countless responses flooding in from individuals claiming to have experienced similar symptoms following the consumption of Chinese food. Subsequent scientific studies appeared shortly after this initial finding that “confirmed” the role of MSG in the development of CRS.3 One such study appeared in 1977 from Harvard Medical School which claimed that 25% of people experienced CRS. By this time, the evidence against MSG was damning and public opinion of the flavour enhancer had turned sour.⁴ Despite the growing evidence of the negative impacts of MSG, many scientists remained skeptical and upon further investigation, the seemingly ironclad evidence started to unravel. The first study to demonstrate the effect of MSG using a variety of delivery methods was not blinded and had a sample size of only six.5 The study conducted at Harvard included leading questions such as “Do you think you get Chinese restaurant syndrome?” and listed the potential symptoms, creating recall bias.4 Another study conducted on individuals claiming MSG sensitivity found that when given more than 2.5 grams of MSG, participants began to experience headache and flushing.6 However, this is a

VIEWPOINT rather large dose—equivalent to about 200 grams of Parmesan cheese—and was given on an empty stomach, making the scenario rather unrealistic. So, while there are many studies condemning the use of MSG, there are clearly some holes in the narrative and more rigorous evaluation was required.

In 2000, a combined team of Boston University, Harvard University, Northwestern University, and UCLA scientists conducted a double-blind, placebo-controlled study aimed at understanding the true nature of MSG and its side effects. The study recruited individuals with a self-proclaimed MSG hypersensitivity and administered either MSG or a placebo dissolved in a drink.

Subjects were instructed to fast for 8 hours and were given a breakfast after consuming the drink.7 Throughout all research sites, there were no reproducible effects of MSG exposure—individuals reporting MSG sensitivity could not tell when they had MSG or the placebo.

While it is plausible that MSG could cause adverse reactions at high doses and with certain delivery methods, there is no evidence to date supporting the idea of MSG causing CRS, especially when used under reasonably normal conditions.

The U.S. Food and Drug Administration (FDA) has classified MSG as generally recognized as safe (GRAS) since 1958, and despite the overwhelming negative public opinion about the compound, the FDA has never changed its position.8 However, while the scientific community and governmental organizations have come to a consensus that MSG is not harmful, the general public has been slower to change their opinion. Figure 1 shows the results of a survey conducted in 2018 by the International Food Information Council (IFIC), an industry-funded non-profit organization. The survey shows that over 40% of U.S. consumers still actively avoid MSG, demonstrating that MSG is still a greatly feared product, right behind artificial additives, preservatives, sodium, and sugars.⁹ With science defending the effects of MSG, why is the general public maintaining such a strong stance?

The nocebo effect—negative expectations causing more negative effect than would otherwise occur—is likely the main culprit for individuals claiming MSG

hypersensitivity. The same survey from the IFIC shows that consumers no longer trust traditional authorities regarding nutrition and safety, choosing to rely more on personal experience, anecdotes from friends or family, and health blogs.9 Food companies now proudly place “No MSG Added” stickers on their products to hold on to their share of the market which further exacerbates the stigma against MSG. Understanding the reason behind the unmoving public opinion may require a deep dive into the origins of CRS and where the MSG aversion came from—stigmatizing attitudes towards Asian immigrants.

If it was the MSG causing CRS, why were symptoms appearing only after eating Chinese food? MSG has been used for decades in Asia and even in Western cuisine following World War II, yet CRS reports remained isolated to Chinese food specifically. The initial popularization of CRS came at a time of high Chinese immigration rates in the U.S., and Americans were concerned about “exotic, bizarre, and excessive practices” associated with Chinese culture.1⁰ When news broke about a sickness coming from Chinese restaurants, people did not question its plausibility and their deep seeded suspicions about Chinese practices were confirmed. Scientists and laypeople alike were blinded by the narrative of a decidedly Chinese illness caused by MSG and failed to explore why other MSG products didn’t show the same effects. While racist laws barring Chinese immigration to America were removed over 50 years ago, remnants of old stigmatizing attitudes may persist and will likely take more time to completely disappear.

If any of you have actively avoided MSG, you may feel like you have been “fooled” by this misinformation. However, negative attitudes towards MSG have been so pervasive in culture and media that it is hard not to internalize some of those beliefs. Overall, this is a lesson to remain ever skeptical. The claims around CRS seemed credible – studies “confirming” the syndrome were conducted at prestigious institutions and published in influential journals, media sources relentlessly reinforced the idea, and most of the public were adamant in their belief. Like with any form of misinformation, a large part of changing public opinion is raising

awareness around the knowledge gap and educating the public about best practices.

We, as citizens of the world, must always question where ideas come from and the rationality behind those claims, even if it seems like the entire world is behind it.

While CRS may have its roots in racial prejudice, the fear of MSG grew into a health-related consumer fear until it permeated Western culture—something we still feel today over 50 years later.

Consumers still avoid MSG, 50 years later MSG still ranks among the top ingredients that Americans try not to eat, behind artificial additives, sodium and added sugars 0

10

20 30

40 50 60

Added sugars Sodium Preservatives Artificial flavours Artificial colours MSG Caffeine GMOs Gluten Source: International Food Information Council References 1. Sand J. A short history of MSG: Good science, bad science, and taste cultures. Gastronomica. 2005;5(4):38-49.

2. Kwok R. Chinese-restaurant syndrome. The New England journal of medicine. 1968;278(14):796-.

3. Freeman M. Reconsidering the effects of monosodium glutamate: a literature review. Journal of the American Academy of Nurse Practitioners. 2006;18(10):482-6.

4. Reif-Lehrer L. A questionnaire study of the prevalence of Chinese restaurant syndrome. Federation proceedings. 1977;36(5):1617.

5. Schaumburg HH, Byck R, Gerstl R, Mashman JH. Monosodium L-glutamate: its pharmacology and role in the Chinese restaurant syndrome. Science. 1969;163(3869):826-8.

6. Yang WH, Drouin MA, Herbert M, Mao Y, Karsh J. The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study. Journal of Allergy and Clinical Immunology. 1997;99(6):757-62.

7. Geha RS, Beiser A, Ren C, Patterson R, Greenberger PA, Grammer LC, et al. Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate. Journal of allergy and clinical immunology.

2000;106(5):973-80.

8. Meadows M. MSG: a common flavor enhancer. FDA Consumer magazine. 2003.

9. Dewey C. Why Americans still avoid MSG, even though its ‘health effects’ have been debunked. The Washington Post. 2018.

10. Mosby I. ‘That Won-Ton Soup Headache’: The Chinese Restaurant Syndrome, MSG and the Making of American Food, 1968–1980.

Social History of Medicine. 2009;22(1):133-51.

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 27

FACULTY SPOTLIGHT

From China to Canada and beyond:

An inside scoop to Dr. Zhong-Ping Feng’s career, collaborations, and contributions

By Kenya Costa-Dookhan

W

hile her twitter bio states she is a lover of nature and philosophy, Dr. Zhong-Ping Feng’s passions extend far beyond these and into the realms of teaching, researching, and leading. Dr. Feng is a tenured full professor at the University of Toronto, and basic science researcher, and was a medical doctor prior to her career in academia. Within her pre-clinical laboratory at the Department of Physiology, her research, funded by CIHR and NSERC, has focused on ion channels and their roles in neurodevelopmental and neurodegenerative disorders, thus identifying new drug targets for neuroprotection.

Dr. Feng first completed her MD at ZhongShan Medical College in 28 | IMS MAGAZINE WINTER 2020 NEPHROLOGY

Guangzhou followed by a residency in Ophthalmology at Peking Union Hospital at Beijing, in China. During her time as a resident and throughout her fulltime practice, she came to appreciate the disparity for cures to various eye disorders. The lack of therapeutic options available inspired her to pursue exploring new approaches through basic science research and led her to Canada to begin her training as a medical researcher.

She received an MSc in Cardiovascular Pharmacology from the University of Alberta followed by a PhD and postdoctoral training in Neuroscience from the University of Calgary. One aspect which has been central to her success and the success of those surrounding her has been her commitment to mentorship.

From her experiences transitioning

from a mentee to mentor, she stresses the essential components of building a strong relationship between the two are enthusiasm, passion, effective communication, and collaboration, noting that many of these are also key characteristics to being a good scientist.

While collaboration within a university is powerful, what can often be more impactful is collaboration among different universities, especially on the international level. Along with joining the IMS this year, Dr. Feng has also taken on the role of Director of International Development for the IMS, with the goal in mind being to improve the international community of the IMS. She especially understands both the importance and untapped potential of initiatives aimed to

FACULTY SPOTLIGHT

Photo by Kenya Costa-Dookhan

DR. ZHONG-PING FENG, MD, MSc, PhD Professor, Department of Physiology Collaborative Program in Neuroscience Director Director of International Development, Institute of Medical Science

increase the opportunity for international training programs and life experiences, having been both an immigrant to Canada and an international student, and receiving training across two nations: Canada and China. Through her role, she strives to build partnerships with the top universities worldwide and bring new opportunities for graduate students, post-docs, and principle investigators in the IMS to academically explore outside of Canada. The International Development program will also attract international students and faculty to the IMS; ultimately providing cultural diversity and awareness

in an academic setting. Dr. Feng’s next steps are to work towards building international relationships for the IMS with partner schools, as well as potentially establishing an international exchange program. This will help in creating good scientists and mentors, globally.

Dr. Feng is an exceptional mentor, scientist, and professor. Her work thus far illustrates great passions for education, collaboration, and research. When asked how she can make a lasting impact on her field and in the scientific community, Dr. Feng again referred to the importance

of prioritizing students. She described providing students with opportunities to develop their leadership, communication, and research skills as what she viewed as important building blocks for impact in the scientific field and academic community. Dr. Feng’s work, as well as future contributions, will undeniably leave this impact, as her focus lies in connecting students and educators locally here at UofT and on an international level.

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 29

STUDENT SPOTLIGHT

By Natalie Simonian

W

e are living in a time when we are so pre-occupied with checking phone notifications that we forget to pause and enjoy the moment.

From this perspective, practicing mindfulness can be a breath of fresh air. This is how PhD candidate Laura Best chooses to live her life.

Laura Best is an excellent example for enjoying the journey not the destination, seizing emerging opportunities, and helping others where she can. She began her career in research conducting her undergraduate thesis in the lab of Dr. Paul Clarke. It was in Dr. Clarke’s lab where she became interested in translational science which involves using lay language to make science accessible to all. Laura continued her journey into academia at the Institute of Medical Sciences (IMS) where she conducted her masters which transformed into her current PhD project in the lab of Dr. Isabelle Boileau at the Centre for Addiction and Mental Health (CAMH).

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Her PhD thesis focuses on the involvement of the endogenous cannabinoid system in both the risk of developing Alcohol Use Disorder, and the response to treatment.

In the study, Laura runs a neuroimaging clinical trial conducting Positron Emission Tomography (PET) scans of patients at early abstinence from alcohol. The treatment varies per individual, and the study runs concurrently with the participants treatment. While conducting her PhD Laura was also involved in the IMS Student Association (IMSSA) as 2018/2019 Co-President and 2017/2018 Director of Community Outreach. She has also been student lead of the IMS annual events titled “U of T Talks” and the 2019 Ori Rostein Lecture.

Laura’s daily life involves balancing her research with her extracurricular commitments. While the life of a PhD student can be stressful, Laura says her “key to success” is mindful living. As a certified yoga instructor, much of Laura’s methods of stress management come from yoga, meditation, and mindfulness. The

exercises Laura teaches during yoga classes encourage one to take a breath and enjoy the present moment. This can involve practices such as getting off the subway one stop early to take a walk to work, or scheduling time with friends to have a coffee break in between lab meetings.

As an advocate of mindful living, Laura believes it is important to have a positive outlook on life. Laura mentions that sometimes research may not pan out as expected but instead of focusing on the potential downsides of research, she decides to be optimistic and uses obstacles as motivation to succeed.

In her research career Laura attended conferences, received presentation awards, as well as the Canada Graduate Studies CIHR Doctoral Award. She is thankful for all her opportunities but maintains that she would not be where she is if she didn’t prioritize her physical as well as her mental health. Laura states the importance of living in the moment and de-stressing after a particularly busy day.

De-stressing can range from hanging

STUDENT SPOTLIGHT out with friends, getting involved with extracurricular activities, or exercise. For Laura, opportunities to de-stress involve spending time with loved ones and her rescue dog named Riley.

Laura’s mindfulness practices also inform her research. As Laura works with a vulnerable population, a special set of skills are required to be able to conduct research while respecting individual autonomy.

While Laura did receive training to work with vulnerable patients, she explains that when conducting her research, she takes a step back and assesses how the information she wants to convey will be received by each person. “You have to be aware and mindful of how you are coming across and respect each individual” Laura says.

When I asked Laura what her plans were post-graduate school, she told me that she was open to multiple possibilities.

She knows that she wants to apply to a clinical program (medical school, nursing school, or occupational therapy) to eventually become a clinician-scientist; melding her love of interacting with people and her desire to understand human motivations behind behavior.

However, she maintains that wants to be open-minded about her future.

For Laura, graduate school has been some of the most memorable years of her life and she is proud of who she has grown to become in this program. Being involved with IMSSA has allowed her to connect with and form strong relationships in

the IMS grad community, helping and receiving help from other students along the way. Laura left me with these words for present/future IMS students “Remember to breathe. You will get it all done, and you will enjoy the journey.” She mentions that she initially entered graduate school with the mentality that work/extracurricular activities were a checklist of things she “should” be doing. Laura now exits graduate school with a new mentality centered on enjoying the journey, not rushing to get to the destination, and remembering that humans thrive in community and are stronger together.

Photo by Mikaeel Valli

LAURA BEST Institute of Medical Science PhD student

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 31

ALUMNI SPOTLIGHT

Marrying Science and Business

By Rehnuma Islam

Photo by Krystal Jacques

Dr. Rebecca Ruddy (PhD) Business Intelligence Associate at GSK

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ALUMNI SPOTLIGHT

G

laxosmithkline (GSK) is a United Kingdom pharmaceutical company comprised of separate entities that are involved in vaccines, pharmaceuticals, and consumer healthcare. Currently, GSK holds 4% of the pharmaceutical market share, having a significant impact on our everyday life.1 Modern pharmaceutical companies determine in part the direction of health care, provides society with therapeutics, and promises a healthier future. A key factor contributing to the company’s success is its ability to predict the future of healthcare and provide care in fields that have the most promise for therapies. So what guides a company in strategizing products for healthcare?

Dr. Rebecca Ruddy plays a crucial role in forecasting the outcomes of company products based on previous trends and current market variables. Her ability to make assumptions and make predictions about the market relies heavily on the skills developed during her doctoral studies at the Institute of Medical Science (IMS).

Rebecca grew up in Ottawa as the middle child of a family of 5 siblings. Her parents instilled in their kids the importance of higher education. In school, she excelled in the sciences and continued her postsecondary education at McGill University studying Biochemistry. Rebecca knew she wanted to pursue graduate school and for her Masters, she focused on translational research. “I found what I thought was the interesting research and that kind of just naturally led me into neuroscience”. Her quest for good mentorship, laboratory environment, and interesting research topics led her to complete her Master of Science degree in the laboratory of Dr. Amy Ramsey. Rebecca researched the effect of ketamine on alterations in dendritic spine density in different regions of the mouse brain. “My Masters at (the) Ramsay lab was a great experience. I really learned a lot and wanted to stay in neuroscience, but I wanted to explore a different area of it”. She subsequently completed her PhD within the laboratory

of Dr. Cindi Morshead, where she studied, “how to repair and activate stem cells in the brain to improve cognition”. Under the support of “very strong female supervisors”, -a growing field of influential women in science, technology, engineering and mathematics- Rebecca herself took on multiple responsibilities and leadership roles.

While completing her PhD, she became the Co-Editor-in-Chief for the IMS magazine, where her communication and writing skills flourished. She also volunteered for a volunteer consulting agency that allowed her to discover the intricacies of writing a business proposal and developing strategies for project management. To further her business communication skills, she also completed a course called “Healthcare Consulting” at the Rotman School of Management.

Having learned client communication and presented a consulting project during the course, helped during the interview process at GSK. Defending a PhD is daunting, however Rebecca completed her PhD while working for GSK. She applied the skills developed during her PhD to launch her career at one of the largest pharmaceutical companies.

Data is everywhere, from collecting data as a PhD student to making datadriven decisions in the workplace. Thus, it is very important to discern how applicable the data is, when interpreting and utilizing the information to answer pertinent research and societal questions.

At GSK, Rebecca performs this role as a Business Intelligence Associate where she works to answer questions involving various topics such as market share and forecasting drug sales. For example, “How is this brand performing compared to the targets?” This requires gathering the right information from the company’s database and presenting it in a concise and easily understandable fashion. Rebecca’s ability to interpret and communicate data to people from a business background, stems from her experience as a PhD student; where

she developed skills in communicating science towards the general public. This experience was on display when her PhD thesis was featured on BBC World Service’s Newshour programme. Decisions rely heavily on data. The power of reaching the proper conclusions from the data can have gross impact on a company and society. Rebecca’s role as a PhD student has allowed her to approach data interpretation and transformation with integrity. The value from gaining a business background has allowed her to marry business to science and generate data-driven decisions at GSK. Teamwork is important within a large corporation. For her PhD, Rebecca worked alongside lab members in completing projects within the lab. In her current role at GSK, teamwork has become an integral component. Her team at the Mississaugabased division of the company includes an 8-member team, 5 of whom are females, support one another by ensuring unbiased data interpretation and reporting -similar to peer-review. Looking back, Rebecca notes, “I didn’t find that you get lost in the shuffle in a large corporation. I feel very supported in my role and on my team, and you do have a voice which I think might surprise some people when you think about a big corporation”. Her schedule includes many meetings, presentations, and data communication. Outside of work, her friends, and family support her as she grows into her new shoes at GSK. As Rebecca continues in her career, we look forward to seeing Rebecca lead data science towards promising therapies.

References

1. Verdict Media Ltd. The top ten pharmaceutical companies by market share in 2018. https://www.pharmaceutical-technology.com/ features/top-pharmaceutical-companies/

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PAST EVENTS

SURP Research Day 2019 A Great Day of Learning and Discovery

By Sonja Elsaid

T

he 36th Institute of Medical Science (IMS) Annual SURP (Summer Undergraduate Research Program) Research Day was held on August 14, 2019, at Hart House. SURP Research Day was the concluding event of a 12–week summer research program, bringing together undergraduate students from around the globe. This excellent program has been led for almost a decade by Dr. Vasundara Venkateswaran, Professor at the Department of Surgery and Graduate Coordinator and Director (SURP) at the IMS, University of Toronto (U of T).

I had an opportunity to interview Dr. Venkateswaran about the aims and benefits of the program and how the program has evolved over the years under Dr. Venkateswaran’s guidance.

According to Dr. Venkateswaran, the primary aim of SURP is to give undergraduate science and medical students firsthand experience working at the bench and within clinical research at the U of T and its affiliated hospitals. This year nearly 100 students enrolled in the program to conduct research in the number of diverse fields of medical science, including neuroscience, cardiology, infectious diseases, rheumatology, audiology, cancer, ophthalmology, transplant medicine, and pain management. Students attending the program, benefit from the opportunity to test whether medical research is what they want to pursue before committing to a long-term graduate program. For some students, there is also an opportunity to obtain their graduate training from IMS faculty supervising their SURP project.

One of the main advantages of being in the program is the opportunity to

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participate in weekly SURP seminars, journal clubs, and workshops. The seminars are not only rendered by IMS faculty, but by IMS graduate students who readily share their experiences with undergrads regarding graduate research, interaction with supervisors, and the skills and mindset needed to navigate both.

In order to receive the SURP certificate of completion, each student is required to present either a poster or a podium presentation at the SURP Research Day. These presentations are judged by a group of IMS faculty members as well as the IMS graduate students.

Under the leadership of Dr. Venkateswaran’s the number of SURP awards that were presented at the Research Day increased 10 fold. Initially there were only 2 awards, one for the first place and a second for the honorable mention. However, Dr. Venkateswaran’s has in place 2 awards for each group of 10-12 students. Her aim of increasing the number of awards is to motivate the students to pursue research and encourage a healthy competition among the students. Furthermore, at each SURP Research Day many excellent posters and presentations are regularly delivered, so it is difficult to select 2 winners among nearly 100 students. The winners are presented books that are personally selected by Dr. Venkateswaran. These new implementations to SURP are a reflection of Dr. Venkateswaran’s generous nature and her dedication in educating both undergraduate and graduate students.

This year’s SURP Research Day commenced with a welcome note from Dr. Mingyao Liu—Director of the IMS and Professor of Surgery, Medicine, and Physiology at the Faculty of Medicine,

U of T, followed by introduction of the Keynote speaker by Dr. Venkateswaran.

Michelle Dubinsky, Ph.D. student at the IMS, was the Master of Ceremonies and helped coordinate the research day.

Dr. Alan Kaplan delivered an excellent keynote presentation titled: “Genes or Jeans? The Etiology and Treatment of Anorexia Nervosa”. Dr. Kaplan is the Vice-Dean of the IMS, Senior Clinician/ Scientist, Chief of Research at the Center for Addiction and Mental Health, ViceChair for Research and Professor in the Department of Psychiatry at the U of T. His presentation described the latest research findings on genetic predispositions to Anorexia Nervosa and how these predispositions, in combination with psychological, socio-cultural, and environmental factors, contributed to the pathogenesis of the disorder. Dr. Kaplan’s presentation was followed by six podium presentations by students on the topics of brain injury, psoriatic arthritis, clinical trials, Chinese medicine, acute myeloid leukemia, and diabetic retinopathy.

The afternoon session included excellent poster presentations by the remaining 94 undergraduate students. I spoke to a few students about their experiences in the program. Ming Mao—a thirdyear medical student from Shandong University in China—joined the program because he was specifically interested in U of T’s cutting-edge research in epilepsy and neurodegenerative disorders. Ming enjoyed his summer research experience so much that he expressed an interest in pursuing his graduate training at the IMS after completing his medical degree. Ming’s project was on histological verification of a novel non-lesioned seizure mouse model, which he conducted under the supervision of Dr. Liang Zhang—the

PAST EVENTS Photos by Nathan Chan

Associate Professor of Neurology and an Affiliate Scientist at the Krembil Research Institute. Sandra Vijayan—a first-year medical student from Dublin, Ireland— joined the program because she wanted to get her firsthand experience in research.

She worked under the supervision of Dr. Nigil Haroon—the Assistant Professor of Medicine and Rheumatology and Clinician-scientist at the Toronto Western Hospital and Krembil Research Institute.

Her summer research was on ossification in ankylosing spondylitis under hypoxic conditions. Sandra described her experience as “revelational” and she was very much inspired being mentored by senior graduate students in Dr. Haroon’s lab. I also interviewed Karen Arevalo—a third-year undergraduate student from McMaster University—enrolled in the Integrated Science program. During the interview, Karen shared her struggles with getting a summer research job due to the large number of applicants interested, while there is only a limited number of summer research positions available.

Being previously unsuccessful in getting the summer research position, Karen spent her summers working as a waitress.

This year, Karen decided to test her luck and reach out to all potential supervisors

working in the scientific research at the U of T—near her home residence in Vaughan. She was fortunate to be recruited by Dr. Aaron Schimmer—Senior Scientist and the Director of Research Institute at the Princess Margaret Cancer Centre. Karen’s firsthand experience working in Dr. Schimmer’s lab with the animal model of acute myeloid leukemia was transformational, as after completing the 12-week program, Karen decided to pursue academic research as her longlife career. While attending the SURP program, Karen mostly enjoyed the weekly speaker seminars, interacting with the IMS graduate students and learning “the art of presenting research,” which she learned quite well, since Karen was the podium presentation winner.

students received honorable mentions, as they were runner-up winners in each competition category. For the first time this year, Jasmine Quigley Memorial Award was given at the SURP. The award was created to support the excellent work of an undergraduate summer student whose project was related to the topic of biotechnology as applied to neuroscience/ mental health field.

Aside from Karen Arevalo’s first prize podium presentation, during the award ceremony, 11 other undergraduate students received first prizes for their excellent poster presentations. The first prize poster winners were: Roshanak Asgariroozbehani, Leon Chi, Tiffany Got, Sae Hoon (Dave) Gwun, Seung Heyck Lee, Benjamin Liu, Michael Peng, Jared Riviere, Joelle Soriano, Sandra Vijayan, and Qin Yi (Teresa) Zhu. Also, 12 other

After yet another successful SURP Research Day, Dr. Venkateswaran congratulated all the students on successfully completing their projects and thanked the IMS administrative staff, graduate students, judges, and sponsors who contributed to making the event possible. Overall, SURP Research Day 2019 was a great day of learning and discovery.

The first recipient of this award was Lara Murphy, who presented a poster titled: “Gene-drug pairing for antidepressants and antipsychotics: A review of the level of evidence using expert consensus recommendations.” The Quigley family presented the award shortly before the conclusion of the event.

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SECTION TITLE HERE PAST EVENTS

By Laura Best and Alexa Desimone

I

t was summer 2019. Across the desk sat Vasu Venkateswaran, smiling after catching me up on the current status of the Ori Rotstein Lecture in Translational Research. She looked at me and asked “Ok, given the title of the lecture, what do you want the panel discussion to be about?”

The lecture title was long, daunting even, and clinically specific, but what stood out to us were the first two words: “my journey”.

One of the most cliché phrases my mother imparted on me was that life is not about the destination, but the journey. As a child who followed the common progression from elementary to university, this wisdom had very little meaning. My academic life existed separately from my personal life, serving the sole purpose of getting me to my future career. Life used to function more like a checklist than a journey. Yet, somewhere along the way this changed.

Unexpected obstacles and opinions made me rethink previous decisions, predetermined timelines extended and shrank, priorities shifted as new people and opportunities presented themselves.

However, this is common and rarely do students embark on a linear track that leads them to their predetermined finish line without turns or hurdles. These twists and hurdles often make one stronger and more innovative. I learned that this is the journey, and that is what we wanted to be the focal theme of this year’s Ori Rotstein Lecture.

On October 4th, 2019, the Institute of Medical Science (IMS) held their annual

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Ori Rotstein Lecture in Translational Research, and for the first time, us as students were involved in the planning.

We had the pleasure of hosting surgeonscientist and IMS alumnus Dr. David Hackam as our keynote speaker, followed by a panel discussion highlighting journeys through research. Dr. Hackam is the Chief of Paediatric Surgery and Paediatric Surgeon-in-Chief at Johns Hopkins Children’s Centre, but truthfully, he should consider a side career in comedy.

“In this business we are invited to give talks often, but it is rare that you get to speak with family, in front of those who played a huge role in getting me to where I am today” - Dr. David J. Hackam Surrounded by a number of mentors, the talk began with a full-circle story. A quote from Dr. Rotstein, “I’ll make you famous, come and work for me”, initiated Dr. Hackam’s journey from a struggling graduate student to a surgeon-scientist working at a world-renowned hospital.

After completing his residency and doctoral studies, Dr. Hackam began his paediatric fellowship at the University of Pittsburgh.

It was there, where he met a family whose son, Freddy, was diagnosed with necrotizing enterocolitis (NEC). This clinical encounter inspired his life’s research focus: a cure for this devastating disease.

In 2014, Dr. Hackam was recruited to Johns Hopkins Hospital as Chief of Paediatric Surgery and Co-Director of

the Children’s Centre and began to dive deeper into his research focus. NEC is one of the most common fatal diseases of the gastrointestinal tract, affecting 2-15% of premature infants. Originally, scientists thought NEC was caused by immune system dysfunction secondary to prematurity. However, Dr. Hackam and his surgical colleagues focused on the intestines and the bacteria-endothelium interaction. After the discovery of toll-like receptor 4 (TLR4) on the endothelium of premature babies, they hypothesized that this immune receptor, when exposed to bacteria, overreacts, leading to cell death and the decay of the intestines.

Dr. Hackam considered why the developing gut would have a receptor that had such devastating impacts if it didn’t function properly. The answer lies in the fact that the premature baby is exposed to an abnormal environment. In-utero, TLR4 acts as a critical gut development regulator, but when TLR4 continues to be expressed postnatally it becomes a destructive inflammatory receptor. Fortunately, breast milk is known to be protective against NEC development; various molecules within breast milk are able to reverse NEC through inhibition of TLR4, which prompted Dr. Hackam to explore if medications could do the same. A TLR4 inhibitor was the first approach, and him and his team identified a molecular compound, C34, which effectively inhibits TLR4 in NEC animal models.

PAST EVENTS

Photos by the IMS Office

“In this business we do get to give talks, but it is rare that you speak with family, in front of those who played a huge role in getting me to where I am today.” - Dr. David J. Hackam

When patients survive NEC, they are typically left with long-term cognitive deficits. Dr. Hackam has identified the underlying mechanism demonstrating TLR4’s control of these deficits. He has shown that TLR4 in the gut leads to the release of molecules that activate microglia in the brain, leading to cell death and demyelination. A novel formulation which contains complexes to directly distribute TLR4 antagonists to the brain is a therapeutic strategy that he is currently pursuing.

Ultimately, being in an institution such as Johns Hopkins, with an abundance of resources available, Dr. Hackam had the opportunity to carry out his research to its full potential. Dr. Rotstein said, “You take the first job, to get the second job”, and this rang true for Dr. Hackam as pivotal advice in his career trajectory. If it wasn’t for Pittsburgh and meeting Freddy, Johns Hopkins would not have recruited him, and he would not have, over 20 years, developed five possible therapies for the treatment of NEC. Following the keynote, the panel discussion was moderated by Dr. Ori Rotstein himself, and featured Dr. Shelley Boyd, Dr. Samantha Anthony, Dr. Sunit Das, Laura Best and Dr. David Hackam. Diversity of experience was the intention behind panelist selection, yet a commonality between panelists and audience members alike was a passion for science and research. This common ground led to an inclusive environment

and dynamic conversation between panelists and students.

The discussion began with an invitation for each panelist to talk about their own journey including a hurdle or pivotal moment. Dr. Boyd, an entrepreneur and ophthalmologist at St. Michael’s Hospital, is the founder of biotech company Translatum Medicus Inc, and previously worked in the pharmaceutical industry at Novartis. Dr. Anthony, an IMS alumnus and clinician-scientist at SickKids, shared her experience forging the path as Canada’s first clinician-scientist with training in social work. Dr. Das, a neurosurgeon at St. Michael’s Hospital, shared the benefits of innovative thinking and cross-disciplinary training with his degrees in english literature and philosophy. Laura Best, a current PhD student in IMS, has held numerous leadership positions, sits on the board of a charity for women’s brain health, and is striving to learn all she can during her time in IMS.

noses to see what worked for them. (3) You have to like what you do because life is long. (4) Work hard, but balance is important. (5) Finding the right role model or mentor can be a game changer.

As graduate students ourselves, we are still in the process of learning and exploring our fields. Our experiences differ as we consider our unique perspectives and circumstances.

What is common, though, is the existence of unpredictable influences on these experiences and that our unique strengths help us navigate our own journeys. For us, one thing we know is that planning the Ori Rotstein Lecture was not in the original plan, but it was definitely an impactful chapter in our journey here at IMS.

Students in the audience asked a variety of questions to the panelists, ranging from advice for navigating an early career in science to the panelists’ favourite books.

When the discussion reluctantly came to an end, Dr. Rotstein shared some of the commonalities he heard amongst the journeys: (1) Incredible optimism and persistence are essential characteristics to success. (2) To a certain extent, many of the panelists’ experiences were not preplanned, instead they followed their IMS MAGAZINE SEASON YEAR ISSUE THEME | 37

TRAVEL BITES

Photos by Mikaeel Valli

By Mikaeel Valli

O

n Tuesday April 4th, 2019 at 1:17 pm, an email appeared in my inbox titled “IBRO Award Notification.” I quickly opened the email to discover that I was selected to receive the 2019 World Congress Travel Award.

This helped to fund my attendance at the International Brain Research Organization (IBRO)’s 10th conference held in Daegu, South Korea happening in September 2019! Words cannot describe how ecstatic and honoured I was to receive this email.

I applied to this funding opportunity thinking there was nothing to lose, but I did not think I would be selected for this award.

Five months passed since the nomination email and I was on my way to South Korea.

After a grueling 14-hour flight, I took a three-hour bullet train ride from Seoul to Daegu; which is located south-east of the country. It was literally a 24-hour journey from leaving my home in Toronto to entering my Airbnb in Daegu.

The next day was the start of the fourday conference, which was rich with keynote speakers who were sharing the latest updates of their research, many

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informative symposiums and thousands of posters. I appreciated how IBRO provided a platform for attendees to access the wide-ranging topics in neuroscience beyond our research focus. Topics ranged from the cellular level to macroscopic whole brain level to brain disease impact on the population level. Through conversations with a diverse community of neuroscientists from many continents around the world, I realized that despite the far distance that lay between us, we share similar difficulties, challenges and experiences in neuroscience research.

I appreciated the efforts made by the conference organizers to share both science and the Korean culture. During their banquet reception, they had a fashion show displaying the beautiful traditional Hanbok outfits—traditional Korean clothing—and Korean musical performances for everyone to experience.

In addition, IBRO also partnered with the Korea Tourism Organization to provide guided tours to many must-see destinations. I visited two United Nations Educational, Scientific and Cultural Organization World Heritage Sites near

Daegu. In Gyeongju, it contained the beautiful and colorful Bulgaksa temple while in Hapcheon, it had the Haeinsa Temple. This location is home to the entire Buddha Scripture carved onto 81,350 wooden printing blocks. Following the conference, I dedicated an extra ten days to explore the main sites in South Korea.

I took the bullet train to Busan to visit the large coastal city and smelt the saltwater of the Pacific Ocean. Another highlight was visiting the Haedong Yonggungsa Temple that was intricately built on a cliff by the ocean. Last but not least, my trip ended by travelling back up north to Seoul.

This bustling city with many modern skyscrapers was seamlessly entrenched with historical palaces and temples.

The opportunity to meet diverse neuroscientists around the world at the IBRO conference and to visit the beautiful historical, modern and natural landmarks has made my first trip to Asia a memorable one. I cannot wait to visit Korea again!

BOOK REVIEW

Educated

Beatrice’s Pick

A MEMOIR

By Beatrice Ballarin

T

his year I picked Educated by Tara Westover for my summer readings by the Venetian beaches. I have heard a lot about this book, although I do not usually read memoirs, I decided to see for myself why this book became so popular.

From an Italian perspective, I barely knew anything about the obscure faction of Mormon Survivalists the author was born into- to me, all of this has always been far away on the other side of the ocean. Nevertheless, the stereotypical image that I had of the US is of a land full of opportunities, jobs, prosperity, and big universities. How little did I know that what I was about to read was going to shock me deeply and change my perspective on the States.

There once was a little girl from the remote mountains of Idaho that had never been in a classroom. Born in a poor family of rural Mormon survivalists, she spent most of her childhood preparing for the “end of the world” by canning peaches. Tara was the youngest of seven children being raised outside of modern society-neither her nor her siblings even had birth certificates.

She spent her summers organizing medicinal herbs for her mother, who was a healer and an experienced-but unlicensedmidwife. During the winters, she worked a precarious job in her father’s junkyard, without the use of protective equipment.

Although there were innumerable accidents and injuries, the father’s mistrust for western medicine prohibited access to hospitals and instead relied on home remedies. Thus, the Westover family had never seen a nurse or a doctor before.

Shockingly, car crashes and even major burns from explosions were treated at home through the use of herbs. As the reader, the father’s strict rules and extremist beliefs about the coming “End Times” are difficult to comprehend, but for Tara, it was all she ever knew. Until she started asking questions.

Besides mistrust of mainstream medicine, including hospitals, there was also a fear of the federal government and public education. This led the Westover family to become extremely isolated from mainstream Mormon society, with no one to intervene when Tara was constantly abused and beaten up by her older brother.

There was no one to support her—not even her parents. Only as an adult, and far removed from her homeland, did Tara start to realize that her father might be suffering from bipolar disorder. This tragic combination of events pushed Tara to rebel against her parents’ view of the world and actively seek to educate herself. She started by teaching herself enough math to pass the GRE and get herself admitted to college, where she studied history for the first time.

She recalled an episode during modern history class during her first year at the university, where the professor showed pictures of bony people, looking sad, and wearing what looked like striped pyjamas.

She recounts with embarrassment that she failed to recognize the holocaust in that picture- she’d never even heard of it before.

When she asked publicly in the classroom what was going on in the picture, her cheeks quickly burned with shame for not knowing. In that moment she made a promise to herself to study all that she could about the world that had been kept hidden from her.

And study she did, though not without struggles, she eventually enrolled into a PhD program at the prestigious Cambridge University, all without the support of her family. Her desire to learn changed her; she started to see how the world worked outside the walls of her home in Idaho. Now, she often wonders if she has traveled too far from her family, and if a way home is still possible. It is of no question that her education saved her, literally. Although, to the reader, it appears as if Tara is not quite ready to fully step into this new world and she often feels insecure and even discouraged about her new, “enlightened” self.

Educated is a book about struggle and self-invention. It is about family loyalty and the grief that comes when abandoning it. It describes the background of the rural US, where besides the metropolitan cities like New York or San Francisco, this is still a reality that some face and struggle to escape. It describes, with the heartbreaking emotional distance of a self-emancipated daughter, the people Tara loved but who also wronged her or failed her. It is almost as if she is talking about the past of someone else, as if she fears her memories to be true, because they are terrifying. It describes the power that education has to offer, allowing a person’s to revisit her life through new eyes.

Maybe with this book Tara tried to put all the pieces of her life together, attempting to better understand what happened to her. And to, with respect, ultimately forgive and be able to break away from the umbilical cord tying her to her past and be free. As she puts it, in the last line of the book: “You could call this selfhood many things. Transformation. Metamorphosis.

Falsity. Betrayal. I call it an education”.

“Curiosity is a luxury for the financially secure.”

IMS MAGAZINE WINTER 2020 NEPHROLOGY | 39

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