A Conversation with MoGen Postdoc Dr. Ugo Dionne

A Conversation with Postdoc Dr. Ugo Dionne

As the newly elected co-president of the MoGen Graduate Student Association, I had big dreams about how I wanted to contribute to reshaping our department. One of my key initiatives is a project aimed at strengthening the bond between postdocs and the department. This interview aims to highlight the achievements of postdocs and inspire graduate students to explore various career paths, broaden their perspectives, think outside the box, and strive for more. Additionally, I aim to emphasize the valuable insights and experiences that postdocs from diverse backgrounds bring to our department. Their perspectives can help us navigate through challenges and make informed career choices. In my experience, interacting with postdocs has been incredibly enriching, and I want to extend this opportunity to more students.

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This piece highlights the story of Dr. Ugo Dionne, a postdoctoral research fellow in Dr. Anne-Claude Gingras's lab at the Lunenfeld Tanenbaum Research Institute (LTRI). Growing up in Montreal, Dr. Dionne completed his undergraduate degree in biochemistry in Quebec City. He pursued his master's and PhD in cellular and molecular biology at Laval University, focusing on a specific type of protein domain called SRC Homology 3 (SH3) under the supervision of Drs. Nicolas Bison and Christian Landry. For his postdoctoral research, he decided to learn new approaches in proteomics with a focus on mass spectrometry. His current project centers on oncogenic fusions and cancer. Ugo moved to Toronto in 2021, aspiring to become a principal investigator and establish his own lab to mentor future generations of scientists. He is actively involved in committees at the LTRI and has directly mentored 6 graduate and undergraduate students throughout his early research career.

Ugo, could you share some insights into your scientific research and the project you're currently working on?

My project is centered on understanding the roles of kinases in cancer, particularly when they become dysregulated or altered. Kinases are master regulators in our cells, acting as switches that respond to specific signals and initiate cascades leading to changes in gene expression and cell behavior, such as migration or proliferation. Normally, kinases are tightly regulated and remain inactive until needed. They become active only in response to specific signals like growth hormones, insulin, or pathogen infections. In cancer, however, kinases are often mutated, leading to their constitutive activation and to cellular proliferation and migration, which in turn contributes to cancer formation. 

I’m particularly interested in a specific alteration called translocation, where chromosomes break and reattach incorrectly, creating fusion proteins. These fusions can sometimes provide a survival advantage to cells, leading to cancer. A well-known example is the Philadelphia chromosome in chronic myeloid leukemia, where the BCR-ABL1 tyrosine kinase fusion leads to increased proliferation. Targeting this fusion with kinase inhibitors has been a remarkable success story, with many patients achieving long-term remission since the FDA approval of the first kinase inhibitor in 2001 (Imatinib). Despite this success, there are over 1,000 different kinase fusions that have been identified in cancerous cells, many of which we know little about. 

While some kinase inhibitors show initial effectiveness, cancers often develop resistance because inhibiting one kinase can create selective pressure for cancer cells to activate other kinases, leading to relapse. The goal of my project is to better understand how these kinase fusions rewire signaling pathways to design more effective therapies. In our lab, we use a technique called BioID for proximity proteomics. We fuse a biotin ligase to the kinase fusion, which allows us to identify proteins in close proximity. We then use mass spectrometry to identify these proteins and determine which signalling pathways are affected. By building a collection of different kinase fusions using BioID and phosphoproteomics, I aim to map out the signalling rewiring caused by these fusions. Additionally, I test the effects of kinase inhibitors to see which proteins continue to interact with the fusion proteins once the kinase domain is inhibited. My research also involves microscopy to observe the localization dynamics of these proteins. Ultimately, the next step is to identify key scaffold and adaptor proteins that are consistently recruited by these fusions and test if targeting these proteins can inhibit the cancer-promoting activity of the kinase fusions. This approach could lead to more effective combination therapies that prevent the rapid development of resistance.

What motivates you every day? What drives you to pursue your work here beyond the pressure of publications?

Well, it depends on the day, but most of the time, it's the drive to continue my project and see it through to completion. In science, there are exciting moments between points A and B, but a lot of the work involves routine experiments. The excitement of discovering the final answer is very stimulating to me. Additionally, ensuring that experiments are done correctly to yield interpretable data is important, even if it involves tedious quality control steps.

Another significant motivation is my aspiration to become a PI and lead my own lab. There is pressure to publish impactful research in major journals, and timing is critical. I can't delay this process indefinitely.

On a more personal note, there's the aspect of starting a family. While there's no perfect time to have kids, some moments are more convenient than others. Balancing postdoctoral work with the goal of starting a family is challenging. So, part of my motivation is to complete my work efficiently so I can also focus on family life.

Can you share an example of a particularly challenging moment during your PhD when you almost felt like giving up but managed to push through?

That's a good question. I faced many difficult times during my PhD, but I never really had a moment where I wanted to change my mind. Part of this resilience might be because, doing a PhD in Quebec City, there are fewer opportunities to transition into industry or biotechs compared to places like Toronto or the US.

Most of my challenging experiences were related to publishing. Trying to get papers published and dealing with rejections from multiple journals was tough. The reviews could be extremely demanding, requiring months of intense work to address. This pressure was compounded by the need for timely publications for grants and other academic requirements.I remember one particularly difficult time with my second paper. We felt it was a significant finding, but it was 2020, and the focus was, understandably, on COVID-19 research. Our work seemed to be sidelined with rejections piling up. 

Despite these challenges, my desire to have my own lab and mentor younger scientists kept me going. I enjoy generating ideas, testing them, and training new scientists, which is hard to do outside of academia. So, even though the publication process was gruelling, my passion for research and teaching helped me push through those tough moments.

How did you manage feelings of imposter syndrome, if you experienced them, during your PhD?

I believe it's actually important to experience imposter syndrome sometimes. I still have it, and I think I will until the end of my career. It pushes us to strive for improvement and prevents overconfidence. However, it's a slippery slope because if you get too caught up in imposter syndrome, it can erode your confidence and affect you negatively. The key is to balance it. While it's necessary to be humble and not be overly confident about everything in your project, it's equally important not to let imposter syndrome overwhelm you. It’s about maintaining a sense of humility, which keeps you on your toes, but not letting it hinder your confidence and progress.

What qualities do you believe make a great mentor, and what kind of mentor do you aspire to be in academia?

Being a good mentor is challenging, especially in academia, where there are additional difficulties due to the competitive nature of our field. Graduate students and postdocs are often underpaid, and managing a lab with limited funds adds to the stress. You need to be super productive despite financial constraints, and your lab's success depends heavily on your mentees. Balancing the demands of running a lab with the needs of students requires careful thinking, as the pressures of academia can sometimes overshadow the personal development of the students.

I believe the key to being a great mentor is understanding and empathy. Many PIs seem to forget what it's like to be a grad student. They focus on their own pressures and inadvertently pass that stress onto their students. It's important to remember that experiments take time, especially for students who are learning new methods for the first time. A mentor should be patient and acknowledge the learning curve that comes with new techniques. This patience can make a significant difference in the confidence and competence of the mentees.

Additionally, it's crucial to stay up to date with changing norms. For instance, the acceptance of working from home has increased, which wasn't the case during my graduate studies. Allowing flexibility for students to work from home when needed, and being considerate of their personal lives and mental health, is essential. Adapting to these new norms shows that you respect the evolving work environment and care about the well-being of your mentees. Encouraging a healthy work-life balance can lead to more productive and happier students.

Providing opportunities for mentees to take initiative and make their own decisions is also important. They should have the chance to fail and learn from their mistakes without constant hand-holding. This autonomy fosters growth and confidence. Encouraging independent thinking and problem-solving skills is crucial for their development as scientists. Mentors should create an environment where students feel safe to explore their ideas and learn from their experiences.

I think a great mentor should be understanding, adaptable, supportive, and provide opportunities for independent growth. It’s about guiding them to become not just competent scientists, but also confident and resilient individuals.

We are all very interested in issues of Equity, Diversity, and Inclusion (EDI). As a white man, have you experienced any specific benefits or privileges that you are aware of? Could you share your perspective and experiences regarding EDI?

I was fortunate to do my graduate studies in labs with a lot of international students and a good diversity of women, men, and people from different ethnic backgrounds. This diversity was particularly beneficial for me, especially in Quebec City, where the academic environment is quite different from the predominantly white and francophone city. Having this exposure to a diverse group of colleagues enriched my academic experience and broadened my perspective.

As for privileges, being a man in academia does come with certain advantages. There are more male PIs, which can create a sense of camaraderie or a "boys' club" mentality. This can make it easier to form connections and build relationships with male PIs, potentially leading to opportunities such as being selected for talks or receiving recommendations. I can see how female PIs might feel excluded in such environments, especially at conferences, where informal networking can play a significant role in career advancement. Being part of these networks often provides advantages without one even realizing it. For example, friendly interactions at events can lead to beneficial relationships, which might not be as accessible to others. These connections can result in invitations to collaborate on research projects, participate in high-profile conferences, or receive insider information about funding opportunities. Moreover, these advantages can accumulate over time, creating a significant impact on one's career trajectory. Recognizing these privileges is crucial for fostering a more inclusive and equitable academic environment. It's important for those of us who benefit from these privileges to be aware of them and to support initiatives that promote diversity and inclusion. 

In a hypothetical scenario where you are magically in charge of the entire academic system, what changes would you implement to improve academia?

I think that there are many things that could be better, primarily related to grants, scholarships, and the publication process. These are the main areas that need reform. When it comes to publications, the entire system could be improved, which ultimately ties back to funding. For publications, the peer review system is crucial, yet it is flawed. Peer reviews are conducted by scientists who aren't compensated for their time, leading to inconsistency in the quality of reviews. This can result in scenarios where subpar or even fake papers slip through the cracks because the editors or reviewers are overburdened and unable to thoroughly vet every submission.

In my experience, the quality of reviews can vary drastically. Some reviewers provide excellent feedback and insights, while others barely skim the abstract and give a superficial assessment. This inconsistency often arises because reviews are done in the reviewers' free time, usually without any additional pay. As a result, the peer review process can become a lottery, where the quality of feedback depends on who happens to review your paper.Some journals are experimenting with new methods to make the peer review process more equitable. For instance, the rise of preprints allows the broader scientific community to review and comment on papers before formal publication. While this is a step in the right direction, it still has its own set of challenges. The intensity and quality of reviews can vary depending on the community’s engagement with the preprint.

The root of these issues is the lack of funding in academia. With more financial resources, we could, for example, pay reviewers, which would incentivize them to take the time to provide thorough and high-quality reviews. Additionally, providing compensation could attract more qualified individuals to participate in the review process, ensuring a more consistent and equitable evaluation of research. Grant/scholarship reviews face similar issues. Scientists, including postdocs and sometimes even PhD students, review grant/scholarship applications without any compensation. This practice is often justified as good experience for the reviewers, but it essentially exploits their time and expertise. For PIs, reviewing grants can be considered a moral obligation to give back to the community, but it adds to their already heavy workload. To improve these systems increased funding for fundamental research is needed. With more resources, we could provide proper compensation for peer reviewers and grant reviewers, ensuring they have the time and motivation to conduct thorough evaluations. This could lead to more consistent and reliable reviews, benefiting the entire academic community.

What advice would you give to younger graduate students who are just starting their academic journey?

There's advice on the science side, and there's advice on the life side. One of the most important pieces of advice, which I often see people not following, is to maintain good communication with your PI. Take the initiative to communicate with your PI about your project to ensure that you're on the same wavelength regarding both the project itself and your mutual expectations. This is crucial for the quality of your everyday life as a grad student.

A lot of distress among students stems from uncertainty about what their PI might think, rather than from direct communication. This can lead to unnecessary anxiety. Don’t wait for your PI to come to you; take the initiative to approach them, even though they are busy. While it is ideal for PIs to regularly check in with their students, students can alleviate a lot of stress by taking the first step in communication. Effective communication can significantly reduce misunderstandings and anxiety in the lab.

On the science side, it's critical to find a project that you are passionate about. This is especially important when you are choosing your lab. Being passionate about your project can make the challenges of research more bearable and enjoyable. Remember that science is a slow process. Despite the pressure to produce results quickly, experiments take time. The period between having an idea and obtaining results can span weeks or even months.

It's also important to understand that failures in experiments are a natural part of the scientific process. An experiment failing or an hypothesis not being supported by the data doesn't necessarily mean it's the student's fault. Accepting that experiments may fail and that hypotheses might be disproven is crucial for maintaining perspective and resilience in research. Keeping this in mind from the beginning can help you navigate the inevitable setbacks with a healthier mindset.

 If you are a post-doc affiliated with any of the nodes within the MoGen department and interested in being featured in our interview series please send an email to: Saya.Sedighi@mail.utoronto.ca