Investigating the molecular mysteries of cancer

Each year on February 11, we celebrate the United Nations’ – a global recognition of contributions made by women and girls to scientific research and innovation across disciplines. The day also serves to highlight the persistent gender gap within science, technology, engineering, and mathematics (STEM), while encouraging more women and girls to pursue careers in these fields.

Anna Panchenko, who joined Queen’s Health Sciences in July 2019, is committed to advancing science and innovation to positively affect health and well-being. Holding the Tier 1 Canada Research Chair in Computational Biology and Biophysics her interdisciplinary work examines the intricate world of genetic and epigenetic factors—the nuanced interplay between our genes and the environmental conditions that influence them—that influence cancer progression. Specifically, her current research uses computational approaches to understand what causes ordinary cells to transform into cancerous ones.

The Queen’s Gazette spoke to Dr. Panchenko to learn more about her work.

Queen’s Gazette: Tell us about your current role as the Canada Research Chair in Computational Biology and Biophysics. What is the goal of your research program?

AP: In , we are trying to identify the molecular underpinnings of cancer mutations by looking at the processes that lead to their occurrence in DNA, and the impacts of these mutations on cellular function and what is known as “chromatin."

One of the major components of cancer is tightly linked to chromatin. Chromatin is comprised of DNA and proteins and contains instructions on how to regulate processes of gene expression, replication, and DNA damage repair. Errors in the form of mutations can occur either during these processes or due to various environmental factors and can be exploited by cancer cells. It’s important to note that not all mutations observed in patients lead to cancer – most of them are neutral. However, a few driver mutations may impact normal processes and lead to the development of cancer. Our research primarily centers on mutations that occur in sporadic cancers, which are not inherited.

Despite many experimental advancements and the accumulation of a considerable amount of cancer-related data, the field is still dealing with numerous unresolved questions and challenges. One key issue stems from the limited ability to directly evaluate the causal relationship between the presence of individual driver mutations and the clinical phenotype of patients. Another problem is having to distinguish a few drivers among the plethora of neutral mutations, especially since the same mutation may drive cancer under some circumstances and be neutral in another environment. More sophisticated interdisciplinary analytical approaches are needed to do this work.

Our team leverages innovative computational methods including molecular modeling and machine learning techniques. Our work is highly collaborative and interdisciplinary. It thrives on the interplay and synergy between computational methodologies and experimental data, each informing the other and strengthening the applicability of our research, allowing us to address complex questions about the molecular mechanisms of cancer.

Lab members from left to right in the clockwise order: Shuxiang Li, Anisur Rahman, Anna Panchenko, Christos Kapetanios, Yiru Sheng, Daria Ostroverkhova, Daniel Espiritu, Yosef Masoudi-Sobhanzadeh.

Queen’s Gazette: What motivated you to enter this field?

AP: There were two primary motivations driving my interest: Firstly, the dynamic nature of chromatin, which is essential for adapting to ever-changing environments and vital for cellular responses. Aristotle noted a long time ago that life requires movement, and it is fascinating to study how atoms and molecules move in time to perform their specific functions. Even more so – to study how these movements are affected by disease perturbations.

The second motivation stems from the pervasive impact of cancer on individuals and families. Now that we know many cancer alterations are primarily caused by environmental factors, it underscores the importance of exploring the link between chromatin and cancer so we can advance our understanding of this disease and allow for more precise treatment options

Queen’s Gazette: Could you explain the computational methods that you use in your research to analyze the causes of disease progression?

AP: Cancer mutations bring about changes involving just a few atoms. Despite their small scale, these alterations can have far-reaching effects on the extensive chromatin systems. However, conventional experimental techniques are not capable of tracking each individual atom in these systems over time. To bridge this gap and gain deeper insights into the effects of mutations and chemical modifications, we employ molecular dynamics simulations—a technique that allows us to map individual atoms in time.

Additionally, we adopt integrative approaches by combining experimental data with molecular dynamic simulations and machine learning algorithms. Our work builds upon the advancements made by numerous researchers in the field of molecular modeling and machine learning over the past decade. Breakthroughs in high-performance computing have also empowered us to simulate biological systems within biologically relevant timescales.

Queen’s Gazette: In terms of therapeutic strategies, how might your research inform the development of new treatment pathways for precision medicine?

AP: By gaining insights into how mutations disrupt normal cellular functions, we can identify potential therapeutic targets. If we predict driver mutations and their impact on new targets, we then can unveil novel avenues for therapeutic interventions.

Understanding why these mutations are occurring in a patient’s genome is crucial for cancer diagnosis. And, we can further explore how various environmental factors contribute to these mutations’ etiology at the level of DNA and chromatin. In our work, we hope to not only deepen our understanding of the molecular mechanisms of cancer, but also demonstrate the possibilities of driver mutations as biomarkers in personalized therapeutic approaches.

Image by Daria Ostroverkhova and Shuxiang Li. An illustration of hierarchical levels of chromatin starting with the cellular nucleus and zooming into individual building subunits, nucleosomes, and structures was taken from PDB 6HKT. Mutations occur in DNA and some of them lead to cancer.

Queen’s Gazette: As we celebrate The UN’s International Day of Women and Girls in Science, what further steps need to be taken to achieve gender equality in STEM?

AP: I think it’s important that we find ways to embrace diversity, which encompasses a broad range of perspectives and experiences. Focusing on creating an open environment where students and researchers can concentrate on their research endeavors is crucial to the advancement of science. I aim to foster inclusive environments where all individuals, regardless of gender, race, or ethnicity, can focus on their scientific pursuits unhindered. Such an approach not only benefits science but also contributes to a more equitable society.

Queen’s Gazette: What message would you like to convey to aspiring women and girls interested in pursuing a career in science, particularly in computational biology and biophysics?

AP: Maintaining a sense of wonder and awe towards scientific discoveries was crucial for sustaining my motivation. Also, patience, perseverance, and challenging the stereotypes. This is particularly relevant for women and other minority groups, who often confront challenges due to unconscious biases that can influence judgment, even in scientific fields.

Securing support in early career is extremely important, not only from a scientific standpoint but also on a personal level. It often takes the form of mentorship and guidance. Mentors, like captains, can steer our ships in the uncharted waters of the research journey. Engaging in networking activities, going to conferences, and meeting new people are equally important.

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