A UHN-led clinical trial is making important waves in the fight against primary biliary cholangitis (PBC), offering hope to those living with this progressive and often debilitating condition with no known cure.
The lead author, Dr. Gideon Hirschfield, is Director of the Autoimmune Liver Disease Program at UHN’s Francis Family Liver Clinic and Toronto Centre for Liver Disease and holds the Lily and Terry Horner Chair in Autoimmune Liver Disease Research.
PBC, a rare autoimmune disease, wreaks havoc by damaging small bile ducts and causing bile acids to accumulate, leading to inflammation, fibrosis and potentially liver failure. It also can significantly impair patient quality of life.
Toronto General Hospital is home to one of the world’s leading autoimmune liver disease clinics. Dr. Hirschfield, who is also a principal investigator at UHN’s Schwartz Reisman Liver Research Centre and a clinician scientist at Toronto General Hospital Research Institute, was the lead author of this phase 3 international clinical trial that investigated the potential of a new drug, called Seladelpar, developed by CymaBay Therapeutics, as an option for PBC treatment.
The article was published in the New England Journal of Medicine on February 21, 2024, and has received worldwide attention due to the impressive results. Read the NEJM article.
One of the common and debilitating symptoms of PBC is pruritus, or severe itching. More than itching as if from a rash, sufferers describe it has a feeling under the skin, or like having insects crawling on you.
A key welcome result of the clinical trial was not only the impact on liver tests for participants, but also a high number of participants receiving the new therapy reported a notable decrease in the itching sensation, bringing better quality of life.
Currently, there are only two other approved drug therapies available to PBC patients, and one of them can at times make the itching worse. Nearly 40 per cent of patients do not fully respond to treatment, and these patients are seeking treatments that improve the disease and their quality of life.
Patients with PBC can face a lifelong struggle as their disease continues to progress with devastating effects on their quality of life. If PBC progresses too far, liver transplant is the only option for extending life.
“A new treatment option that can slow the progression of PBC, reduce the need for liver transplantation and also improve quality of life by mitigating PBC itch is exciting news that gives new hope to PBC patients,” says Gail Wright, who was diagnosed with PBC in 2012 and is President of the Canadian PBC Society.
Dr. Hirschfield agrees, adding, "this new treatment marks a pivotal moment in the fight against PBC.”
“Not only does it offer hope where options were once limited, but its safety and effectiveness over the course of the 12-month study bring newfound reassurance to patients and providers alike,” Dr. Hirschfield says. “It's a really exciting time for patients with hope that Seladelpar will soon become a new approved drug for patients.”
There is a long and distinguished history of treating PBC at UHN. In 1994, Dr. Jenny Heathcote, founder of the Francis Family Liver Clinic, worked on developing the first therapeutic option, which still works for many patients today.
In 2009, Dr. Hirschfield and colleagues described the gene variants associated with developing the disease, and in 2016 he also contributed to reporting the results of a therapy called obeticholic acid, which is used as a second line agent.
This new exciting work has potential for giving more choice for PBC therapies in the near future. “Research and medicine are about building on the work and discoveries that came before,” Dr. Hirschfield says. “It is genuinely wonderful to help carry on the tradition of finding new ways of slowing the progression of PBC and giving patients better quality of life.”
Dr. Gideon Hirschfield’s research program is generously supported by donors to UHN Foundation.
The RESPONSE study was funded by Cymabay Therapeutics.
Dr. Gideon Hirschfield has consulted ad hoc for Advanz, Cymabay, Escient, GSK, Intercept, Kowa, Mirum, and Pliant.
Gideon M. Hirschfield et al., A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis Biomolecules. 2024 Feb 21 doi: 10.1056/NEJMoa2312100
A study from Princess Margaret Cancer Centre (PM) has found a potential treatment for patients with relapsed or treatment-resistant acute myeloid leukemia (AML) and Myelodysplastic Syndromes (MDS), a group of disorders affecting bone marrow function.
AML is an aggressive cancer where immature white blood cells, called myeloblasts, multiply uncontrollably and disrupt the production of healthy blood cells. Outcomes vary based on the types of gene mutations a patient with AML carries. Although it can be cured in 35-40% of patients under the age of 60 and 5-15% of patients over 60, those with certain mutations, such as in the Tumour Protein p53 gene (TP53), have a median overall survival of 5-10 months. There is no standard treatment for patients with relapsed or treatment-resistant AML.
MDS syndrome, where the bone marrow does not produce enough healthy blood cells, can vary widely in severity, ranging from mild cases that may not require treatment to more serious forms that can progress to AML. The only curative option for these patients is stem cell transplantation.
A protein called polo-like kinase 4 (PLK4) is dysregulated in several cancers, including AML. PLK4 plays a role in regulating cell division and high levels of this protein are associated with poor survival in AML.
“An inhibitor that targets PLK4, called CFI-400945, was discovered in a prior drug discovery program at UHN. Previous research in tumour samples and drug characteristics, such as selectivity, make it a promising candidate for cancer treatment,” says Dr. Karen Yee, Clinician Investigator at PM and senior author of the study. “To examine this candidate, CFI-400945 was tested in tumour models and we conducted a phase I clinical trial in high-risk patients with relapsed and untreatable AML.”
The tumour model studies indicated that CFI-400945 is effective, with a treatment response in cells with TP53 mutations, suggesting that PLK4 is a potential therapeutic target in TP53 mutant AML.
The clinical trial was then conducted with 13 individuals with relapsed and treatment-resistant AML. Gene mutation analysis was available for eight of these patients and indicated that four had mutations in TP53. Patients were treated with CFI-400945 at increasing doses from 64 mg/day to 128 mg/day.
“We found that three out of nine patients evaluated for efficacy saw complete remission. One other patient showed a greater than 50% improvement in white blood cell counts,” says Dr. Yee. “Additionally, of these four patients, three of them had TP53 mutations.”
This study underscores the promising role of CFI-400945 as a potential treatment for a typically challenging form of AML. Manageable side effects, such as enteritis/colitis (inflammation of the small or the large) were noted, indicating a reasonable safety profile. Moving forward, researchers are investigating CFI-400945's efficacy and safety in larger patient cohorts, as well as in combination with other therapies.
This work was supported by The Princess Margaret Cancer Foundation (PMCF). Dr. Karen Yee is an Associate Professor at the University of Toronto.
Dr. Karen Yee has been a consultant for Bristol Myers Squibb/Celgene, F. Hoffmann-La Roche, GSK, Jazz Pharmaceuticals, Novartis, Pfizer, Shattuck Labs, Taiho Oncology, and Takeda; Dr. Yee received research funding from Astex Pharmaceuticals, Forma Therapeutics, F. Hoffmann-La Roche, Forma Therapeutics, Genentech, Geron Corporation, Gilead Sciences, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Novartis, Shattuck Labs, and Treadwell Therapeutics, and received honoraria from AbbVie, TaiHo, and Novartis. For a full list of competing interests, see article.
Murphy T, Mason JM, Leber B, Bray MR, Chan SM, Gupta V, Khalaf D, Maze D, McNamara CJ, Schimmer AD, Schuh AC, Sibai H, Trus M, Valiquette D, Martin K, Nguyen L, Li X, Mak TW, Minden MD, Yee KWL. Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms. Leukemia. 2023 Dec 19. doi: 10.1038/s41375-023-02110-9.
Image showing red blood cells (red) and abnormal white blood cells (white). AML is a blood cancer that originates from cells in the bone marrow that turn into white blood cells. These abnormal cells grow and divide too fast, build up in the bone marrow, and spill out into the blood. (Getty images).
In celebration of the International Day of Women and Girls in Science, the Krembil Research Institute hosted a free educational livestream on Friday, February 9, 2024.
The event, which can be viewed here, attracted more than 4,500 people, including over 2,800 students from more than 100 classrooms, some as far as Ecuador, Columbia, Iceland and Australia!
The event was streamed live by middle and high school students from 14 Ontario school boards, including the Toronto District School Board and Durham District School Board, as well as students at international schools and universities.
Moderated by Dr. Chika Stacy Oriuwa, one of Time magazine’s 2021 Next Generational Leaders and an accomplished physician, spoken word poet and advocate, the livestream featured the following Krembil researchers and health care providers:
● Dr. Tina Felfeli, Donald K. Johnson Eye Institute
● Dr. Nikita Looby, Schroeder Arthritis Institute
● Dr. Nardin Samuel, Krembil Brain Institute
Each speaker gave a short, TED-style talk about what inspired them to pursue a career in science, how challenges and obstacles shaped their scientific journeys, and why they find their careers so rewarding.
The livestream also featured guest appearances from Canadian inventor Andini Makosinski and Canadian aerospace engineer Natalie Panek. These remarkable women shared inspiring messages about the importance of dreaming big and refusing to set limits for yourself.
Sharing her advice for young science-enthusiasts everywhere, Makosinski said, “Be bold in your passions and pursue them fearlessly.”
The event concluded with a lively panel discussion in which the speakers answered questions submitted by participating classrooms.
“As we celebrate the International Day of Women and Girls in Science, we recognize the transformative power of diversity in research," says Krembil Research Institute Director Dr. Jaideep Bains. "We hope that hearing from some of the incredible women on our team inspires young people of all genders and backgrounds to break barriers and apply their unique perspectives to answering pressing scientific questions.”
Want more inspiring stories about women researchers at UHN? Click here to read about some of the women who are advancing health research and innovation across the Institution.
According to the United Nations Educational, Scientific and Cultural Organization (UNESCO), women account for only one third of researchers worldwide, despite representing nearly half the population of undergraduate and graduate students. To address gender inequities in the fields of science, technology, engineering and math (STEM), the United Nations declared February 11 as the International Day of Women and Girls in Science.
On February 11, we celebrate the International Day of Women and Girls in Science—a day to recognize and honour all women at UHN who make invaluable contributions to advancing health research and innovation.
From leading scientists to postdoctoral researchers and administrators, our diverse community significantly contributes to our mission of excellence in discovery for A Healthier World.
Join us in honouring TeamUHN's incredible women who are making an indelible mark in science as we feature the inspiring stories of five remarkable individuals. Let's celebrate their achievements and contributions to advancing knowledge and innovation.
Dr. Jennifer Bell
Ethical issues arising in health care
Bertrand Russell, the founder of analytic philosophy, said: “Science is what you know, philosophy is what you don’t know.”
I took an undergraduate philosophy course on Immanuel Kant’s ethics. That summer I worked at the Joint Centre for Bioethics at the University of Toronto where I saw ethics applied to health practice. From then on, I was hooked.
Our team handles challenging ethical issues in rapidly evolving landscapes like genetics, precision medicine, and AI, collaborating to swiftly understand and apply ethical analyses—a process that proves both thrilling and enlightening. Through this work, we aim to embed ethics and equity across UHN's endeavours, fostering respectful relationships within our community.
As a philosophically trained ethicist, I am a bit on the periphery of the field of science, but I can appreciate the need to have women mentors to model a path for current and future generations of women scientists and to diversify to include other equity-deserving groups. The International Day of Women and Girls in Science is an important way to highlight the achievements of women in science and create opportunities for discussion about ways forward.
We can promote women in science by showcasing their achievements, supporting mentors dedicated to inclusivity, addressing socioeconomic barriers hindering women's access to STEM education (e.g., financial and relational pressures), and implementing equitable hiring and training practices to mitigate career interruptions.
I stand in allyship with women in science and others who are committed to diversifying STEM fields.
My favourite science fact is the Twin Paradox where there are twin sisters, and one travels to a distant star at nearly the speed of light. According to Einstein’s theory of relativity, time runs slower on her spacecraft than it does on Earth; therefore, when she returns to Earth, she will be younger than her twin sister.
I've always enjoyed problem-solving and was drawn to research because it allows me to gain a deep understanding of my work so I can think critically and solve problems.
It is extremely rewarding to know that the work I do is meaningful and could quite literally change lives. When I'm having a tough day or am frustrated that an experiment didn't work, I try and step back and appreciate that all the work that we do is moving us toward the goal of improving patients’ lives.
It means changing the perception of what a scientist is. I can be bubbly, funny, and feminine and still be a smart and capable scientist.
Putting more women in leadership positions is critical, especially for women of colour and from the LGBTQ+ community. Diversity and diversity of thought are so important for inclusion. If women can see themselves represented in leadership, it will help shape how people think about their identity and where they fit in society.
Representation matters and I hope that girls are able to see themselves represented when they see me in the workplace. I hope that when future generations think about women in STEM they think "Duh!"
Dr. Lena Serghides
Maternal and child health within the context of HIV.
Did you know that primate placenta (my favourite organ!) development relies on retroviral proteins integrated into the germ line due to an ancient viral infection? It's my favorite science tidbit!
My earliest inspiration was my grandfather who was a chemist and an excellent storyteller. Later, I was lucky to have incredible mentors like Dr. Mary Ann Fields who taught me science is not a job but a lifestyle; Dr. Sharon Walmsley who taught me that anything worth doing is worth doing well; and Dr. Eleanor Fish who taught me to stand up for myself and not be afraid to ask for what I deserve. I strive to be such a mentor to other women!
My favourite part of my work is data analysis – the data are trying to tell me a story and my job is to figure out what that story is. I am really proud of the work my team has done over the years. We study HIV antiretroviral safety in pregnancy. Our data has helped make the treatment of HIV safer for both moms living with HIV and their babies.
I don't see myself as just a woman in science but as a passionate scientist creating nurturing spaces. I've faced challenges, especially balancing family and science, but I'm pushing for a more inclusive and understanding community.
Women face challenges in advancing in science due to the demanding nature of the field and family responsibilities, particularly during critical career phases. Supportive partners can alleviate this burden, but no woman should have to choose between motherhood and a scientific career. Recognizing and accommodating the time constraints of women with young children can help retain more talented women in science beyond just parental leave policies.
I share the thrill of discovery to ignite that spark in the next generation, especially the awesome girls out there. Science is not just a job; it's a journey full of excitement, and I'm here to make it contagious! On this special day, we express sincere gratitude to women scientists, clinician-researchers, and trainees for their exceptional leadership and unwavering commitment to science, inspiring us toward a healthier world.
Dr. Lingdi (Lydia) Nie
The longest-living cells in the body are neurons, which can live as long as your lifespan.
I was fascinated by the research process and the fact that you can continuously explore new ideas and topics throughout your career. I have a constant desire to expand my knowledge and expertise, so this appealed to me. I am also passionate about exploring unknown disease mechanisms and discovering potential treatments. Making these novel discoveries and guiding students toward research fulfills me and enables me to make a valuable contribution to society.
I'm thrilled by our latest venture: crafting 3D human brain tissue cultures in the lab using stem cells sourced directly from individuals with different neurological disorders. This approach promises a deep dive into the intricate workings of these disorders, unlocking insights into their underlying mechanisms. These models will help in the study of patient-specific approaches and personalized medicine and thus advance UHN’s vision of a healthier world.
It means I am working on the front line to empower women and promote gender equality in science. Although more women are now entering the sciences, efforts are still needed to increase the number of female professors and create a more inclusive and diverse global scientific community.
It is important that female scientists be included in providing mentorship and advice to younger generations, offering them the guidance and support they need to thrive in their scientific careers. One of the big obstacles that women in science face is navigating family planning, which can lead to missed opportunities, or even career pauses, making it challenging to compete in the highly demanding academic world. One strategy to solve this issue is to have flexible work structures, such as remote work, and increased maternity leaves to help women achieve better work-life balance.
I hope to lead by example and show the next generation of girls that we can do and achieve anything through determination. It is also my goal to provide mentorship to young girls in science by advising on professional and career development.
Dr. Mina Ogawa
Conducting research to generate liver-related tissues from human pluripotent stem cells.
In a culture dish, observing cells both multiplying and differentiating is tricky. Yet, the human body accomplishes this feat during development, showcasing the captivating dance of specialization and proliferation.
The transformative power of science to influence global health is what ignited my passion for a career in this field. I am also extremely inspired when I connect with great scientists worldwide and hear about their efforts that laid the foundation for their many discoveries.
It is most exciting when my research contributes to our understanding of disease etiology or therapeutic interventions. I am fortunate to be a part of UHN as it is one of the world leaders in translational research. My work aims to provide benefits to patients in the clinical setting by inventing cellular therapy.
Being a woman in science, to me, signifies resilience, perseverance, and endurance—an embodiment of qualities that not only drive personal success but also serve as an inspiration for others. For me, curiosity is the strongest motivation, and I have three amazing children who support me in this endeavour.
We need to establish mentorship programs to empower women in science, drawing from the impactful guidance of female researchers who have shaped my own journey and highlighted the importance of intergenerational support. This entails combatting gender biases, promoting work-life balance, and ensuring equitable opportunities and recognition in the field.
I have trained young scientists in my lab, many of whom are women, and have seen rising stars in the field. I strive to become a leader in my field whom the next generation of girls could look up to and be inspired by.
More from UHN on the International Day of Women and Girls in Science:
Dr. Kristin Hope is a pioneer in studying the role of RNA binding proteins in stem cell function and cancer initiation. She first became interested in stem cells while she was completing her PhD in the lab of Dr. John Dick, a world-renowned leukemia stem cell researcher and Senior Scientist at Princess Margaret Cancer Centre (PM).
At that time, Dr. Dick’s lab was the first to show that a rare population of leukemia stem cells is the root cause of blood cancer development.
“For me, it was the first introduction into the world of cancer stem cells, and I realized that studying them has incredible potential to bring transformative changes for human health,” says Kristin. During her PhD, Kristin focused on the behavior of leukemia stem cells to identify potential therapeutic insights.
Her postdoctoral work, supervised by Dr. Guy Sauvageau at the University of Montreal, delved into the inner workings of blood stem cell function.
“After studying leukemia stem cells and their behavior, I wanted to understand at a very granular level, how normal stem cells work, so that we can reverse engineer the disease process,” says Kristin. In Dr. Sauvageau's lab, Kristin designed high-throughput RNA interference screens to identify proteins of interest that govern stem cell fate and decision-making.
Kristin's passion for unraveling the biology of malignant and normal stem cells led her to establish her own lab, where she integrates the behavioral understanding of human cancer stem cells with the underlying cellular mechanisms.
Fascinated by this process, Kristin sought to determine whether certain proteins can decide the fate of daughter cells during cell division. In the screening experiment during her postdoctoral study (published in Cell Stem Cell), she found that one of the regulators of the asymmetric division process, Musashi2, is critical for maintaining blood stem cells. The daughter cell that does not receive Musashi2 loses its stemness and becomes differentiated.
Musashi2 also happens to be an RNA binding protein (RBP), which prompted Kristin to investigate this class of proteins more systematically when she started her own lab.
“It has been an interesting discovery that, quite a few of these RNA binding proteins, not just a couple, are overexpressed in leukemic stem cells,” says Kristin. “The focus on RNA regulation in the context of cancer stem cells has not been pronounced, but that is changing.”
The complexity of cancer-driving RBPs
To determine which RBPs might be therapeutic targets for anti-cancer treatment, Kristin’s team conducted a CRISPR screen (published in Blood Cancer Discovery) to identify RBPs that are vital for cancer cell survival but have a minimal impact on normal stem cells if inhibited.
“We have identified 32 RNA binding proteins that are really critical for in vivo leukemia growth,” says Kristin.
Among the 32 targets, one RNA binding protein, ELAVL1, was particularly noteworthy. ELAVL1 binds and stabilizes the RNA transcript that codes for a mitochondrial import protein. This particular protein plays a crucial role in supporting oxidative phosphorylation, a metabolic process that cancer cells depend heavily on for their function and survival.
When the team deleted ELAV1 in vivo, they detected a loss of the import protein and mitochondrial activity, which coincided with a reduction in leukemic stem cells. The study identified ELAV1 as a novel therapeutic target for leukemic stem cells in acute myeloid leukemia, through its regulation of mitochondrial metabolism.
Ana Vujovic, first author of the study and a PhD student at Hope Lab.
Apart from RNA stabilizers like ELAVL1, there is another subgroup of RBPs that can splice RNA, providing diverse instructions for protein production. Kristin’s team also discovered that certain RNA splicing proteins can be targeted to treat acute myeloid leukemia in a study published in Nature Communications.
According to Kristin, RBPs that are important in a full-blown leukemic stage are also found to be important in the early stages. A pre-leukemic condition called myeloid dysplastic syndrome, where 30% of cases progress to leukemia, is marked by disrupted RNA splicing.
“Advancing science is an incredibly creative process,” says Kristin. “Sometimes we need to approach the question from a few different angles.”
Kristin advocates for a working environment that is supportive, collaborative, and inclusive.
Having had kids while running a lab herself, she recognizes that being a scientist has traditionally been a challenging career choice for women. On the International Day of Women and Girls in Science, Kristin speaks to the importance of supporting young parents while they are pursuing a career in science.
“I remember having conversations with young women over the years, who have sat across the desk and said, ‘I don’t know if I should try to be a principal investigator because then I won’t be able to have a family,’” Kristin recalls.
“We should be supporting young parents so that they can thrive in the lab and have a family at the same time. The unique challenge that a woman principal investigator can face is when she is on parental leave with a very young child and at the same time trying to manage a lab on top of everything else. Creative solutions to support them during their leave can be a huge game-changer. Likewise, we should also recognize and support men who take parental leave to care for their children.”
“Being cognizant of people's personal lives, whether they are men or women, a parent or not a parent is important. I think that we need to do more in terms of setting boundaries and allowing people to have and enjoy their personal time.”
“I hope as a research community we can foster an environment where people don’t have the ‘scientist or family’ conversations anymore. There shouldn't be a question about whether you can have a family while doing this job. You can.”
Meet PMResearch is a story series that features Princess Margaret researchers. It showcases the research of world-class scientists, as well as their passions and interests in career and life—from hobbies and avocations to career trajectories and life philosophies. The researchers that we select are relevant to advocacy/awareness initiatives or have recently received awards or published papers. We are also showcasing the diversity of our staff in keeping with UHN themes and priorities.
Researchers at UHN’s Princess Margaret Cancer Centre (PM) have revealed that a protein called Topoisomerase 1 (TOP1) — a regulator of DNA organization — can be used as a target for treating cancers involving the MYC protein.
MYC is a regulator of gene expression, which is a process where genes are encoded into proteins. MYC is known to be dysregulated in most human cancers and drive aggressive disease. “Although the inhibition of MYC can block tumour growth in lab settings, targeting it directly in humans has proven to be a challenge with no small molecule inhibitors of MYC advancing to patient care,” says Dr. Linda Penn, Senior Scientist at PM and senior author of the study.
“To effectively target MYC and inhibit its function, we decided to employ an alternate strategy and identify specific proteins or processes required for MYC to function as a potent cancer driver,” says Peter Lin, Doctoral Candidate at the University of Toronto and co-first author of the study.
The researchers used a gene-editing tool called CRISPR to systematically disable the function of different genes in breast cancer cell models where MYC is dysregulated. They then observed which genes were critical for the survival and growth of these tumour cells.
“We identified several genes that encode proteins responsible for proper DNA organization, called R-loop regulators,” said Dr. Corey Lourenco, former Postdoctoral Researcher in Dr. Penn’s lab and co-first author of the study. “We focused on one of these, TOP1, due to the availability of FDA-approved TOP1 inhibitors that are currently used as cancer treatments.”
R-loops are DNA structures that can occur during gene expression, playing crucial roles in gene regulation and maintaining genome stability. Regulatory proteins like TOP1 are important in controlling the initiation or resolution of R-loops, thereby averting potential issues that could lead to DNA damage.
“Upon further investigation, we confirmed that TOP1 was necessary for MYC-driven tumour growth in breast cancer cell models. One way we did this was by inhibiting TOP1 genetically and through the use of medications,” says Dr. Penn. “We were able to show that inhibiting TOP1 reduced tumour growth in our MYC-driven breast cancer models.”
In addition, by examining publicly available datasets, the team found that cancer cells with elevated MYC gene activity were the most vulnerable to TOP1 inhibitors (e.g., topotecan) and this discovery was further validated using patient-derived samples.
Motivated by the prevalent nature of MYC in driving cancer, the researchers propose a model where TOP1 is needed for MYC to drive tumour formation. This suggests that breast cancer cells with high MYC activity rely on TOP1 to resolve R-loop structures and are thereby vulnerable to treatments that block TOP1 and potentially other R-loop regulators. As several TOP1 inhibitors are clinically available, these findings open new potential therapeutic strategies for these types of cancers.
This work was supported by the Canadian Institutes of Health Research, the U.S. Department of Defense, Instituto de Salud Carlos III, Generalitat de Catalunya, CERCA Program to IDIBELL, and The Princess Margaret Cancer Foundation. Dr. Linda Penn is a Professor at the Department of Medical Biophysics, University of Toronto.
Co-author David W. Cescon is a consultant, on the advisory board of, and/or reports funding to AstraZeneca, Exact Sciences, Eisai, Gildead, GlaxoSmithKline, Inflex, Inivata, Merck, Novartis, Pfizer, Roche, Saga, Guardant Health and Knight. Dr. Cescon also reports a patent for methods of treating cancers characterized by a high expression level of spindle and kinetochore-associated complex subunit 3 (ska3) gene.
Lin P*, Lourenco C*, Cruickshank J, Palomero L, van Leeuwen JE, Tong AHY, Chan K, El Ghamrasni S, Pujana MA, Cescon DW, Moffat J, Penn LZ. Topoisomerase 1 Inhibition in MYC-Driven Cancer Promotes Aberrant R-Loop Accumulation to Induce Synthetic Lethality. Cancer Res. 2023 Dec 15;83(24):4015-4029. doi: 10.1158/0008-5472.CAN-22-2948. PMID: 37987734; PMCID: PMC10722143.
* Contributed equally to this article.
Topoisomerases manage the structure of DNA (e.g., the twisting and unwinding of DNA strands) and are important for many biological processes such as DNA replication, gene expression, and DNA organization. (Getty images)
At the end of 2023, UHN held its inaugural Pride in STEM (Science, Technology, Engineering, and Math) event: a panel to celebrate the life and sciences of 2SLGBTQIA+ people in STEM.
Hosted by Dr. Brian Hodges, Executive Vice President, Education & Chief Medical Officer at UHN, the virtual panel provided the opportunity for members of UHN and the public to learn from panelists about what it is like being a queer person in the sciences.
The panel was organized by UHN’s Research IDEA committee (Inclusion, Diversity, Equity, and Accessibility) and included the following panelists:
One major topic of discussion was how the identities of being a scientist and a member of the queer community intersect. Speakers shared what makes their research meaningful to them and to the 2SLGBTQIA+ community and discussed what it feels like to be a part of both the queer and science communities.
“As scientists, the work we do can have ethical and social meaning, especially within the 2SLGTBQIA+ community. This can particularly ring true when researching diseases that may be marginalized because of the communities they are associated with,” noted Dr. Hodges.
Discussions also touched upon coming out in professional settings, such as institutional, university, or lab environments, and how this is complex for many individuals.
While Dr. Gerd Prehna spoke about the importance of being open and visible as a faculty member to enhance representation, panelists also brought up the specific burden for queer people of needing to repeatedly come out in new social spaces. Panelists emphasized that levels of comfort with disclosure vary between different situations such as sharing with friends, colleagues, and the public.
Additionally, panelists acknowledged that despite their comfort and certainty in being “out”, fear and nervousness can persist regarding speaking publicly about one’s identity, even for prominent members of the 2SLGBTQIA+ community and in seemingly progressive times. One panelist noted an inner moment of hesitation when being invited to the panel and being a visible part of the 2SLGBTQIA+ –focused event, highlighting the ongoing challenges of having a marginalized identity.
Panelists agreed that events like Pride in STEM are important in making sure that everyone is welcome within the science community. “Science is for everyone, and it is crucial to have events within the science community where you can be open about who you are and however you identify,” said Dr. Siriwardena.
In addition to events like these, the panel discussed other ways the science community can create an inclusive space such as visibly identifying your environment as a safe space, welcoming people into the lab to express all parts of who they are, and actively addressing hurtful or discriminatory comments.
Improvements are also still needed in other areas. “Resources on campuses are sometimes mainly geared towards undergraduates, leaving other employee groups in need of more support,” noted Sydney O’Brien. In addition, there are currently no awards and/or fellowships that specifically recognize queer scientists. Lobbying funding agencies and universities for this type of acknowledgment is a necessary next step.
To learn more about these topics watch the full panel discussion, click here.
The IDEA committee is also planning an Accessibility in STEM panel for spring 2024. Stay tuned for more details when they become available.
For more information about IDEA at UHN please contact firstname.lastname@example.org.
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