Interview with Dr. Esther Verheyen

Professor, Department of Molecular Biology & Biochemistry

Drosophila developmental genetics

Our cells contain proteins that regulate how often a cell divides and when to stop dividing. Cell division is highly regulated and if it becomes uncontrolled, cancer can develop. Dr. Verheyen’s research group studies how cells are directed toward a particular fate, becoming a specific type of tissue. As much as Dr. Verheyen is interested in what causes cancer, her foremost concern is understanding the fundamental processes behind it, the mechanisms that drive organ growth and cell proliferation, the process of making more cells. This knowledge will position us to understand how dysfunction of normal processes leads to cancer.

What is the most satisfying part of the work you do?
It’s very satisfying when you discover a new role for a gene that you've been studying, when you discover how that gene works. Progress is incremental, but the small results give information that makes you think about the bigger picture, and how to design another experiment to learn more.

Your group studies the role of Hipk in tumorigenesis, as well as the Wnt signaling pathway – how does research in those two areas pertain to cancer?
When you develop cancer, a mutation has occurred that causes the cell to divide uncontrollably. These same cellular mechanisms function in normal development, but in cancer they are not as tightly controlled.

Dysfunction of the Wnt signaling pathway is associated with cancer. When Wnt signaling is abnormally active it causes colon cancer and other problems. We know that the homeodomain interacting protein kinase (Hipk) helps the Wnt pathway do its job in the cell to promote growth. We speculate that if we could block Hipk in cancer cells, then we could minimize the severity of the cancerous growth.

How do you use flies to study the role of these pathways in cancer?
Our research aims to link what Hipk and other proteins are doing normally during development with what happens in cancer. We have found that Hipk contributes to tumor formation. We use the fruit fly (Drosophila melanogaster), which has many of the same genes that when mutated, cause cancer in humans. We have mutant flies that form tumors and in the future, we plan to test different chemicals, drugs and small molecules to ask whether we can reverse tumor formation in the flies – that would be a first step.

As a fundamental research group, we would establish collaborations with cancer labs to test our compounds on cancer tissue samples to identify molecules with therapeutic potential. That is a long process; first we need to understand the basic biology. Our findings that alterations in Hipk can modify the tumors is novel, and our next step is to learn how to control Hipk protein, when and how it acts.

Which project in your lab is advancing most quickly right now?
We are learning a lot about how the Hipk protein is regulated. We are studying where this protein is in the cell and are interested in whether it plays different roles within the nucleus or in the cytoplasm. We are trying to identify other proteins that may control when Hipk can act and how much Hipk protein is present in the cell at any one time. Given that it is a very potent promoter of cell division and organ growth, it seems important to regulate it so that it doesn't go haywire and cause defects and disease.

We are also making progress on understanding regulation of the Wnt signaling pathway. We are looking at how cells establish their fate, their identity within a tissue or organ, and are trying to understand how cellular tension can feed into that. For example, we have found that if a cell is constricting, it has an effect on the Wnt pathway that is different than when the cells are more relaxed. This is a novel observation and we are getting very positive feedback from the scientific community on these findings. Right now we want to understand that connection mechanistically, that is, identify which proteins act together to make this happen.

What research obstacle keeps you awake at night?
The funding situation in Canada right now is very dire. When you are trying to secure funding for your research program, the idea of potentially laying off your staff keeps you up at night. The current emphasis of funding agencies is to have a translational aspect to research, meaning that it should have an immediate health impact. This is short-sighted because most medical breakthroughs arise as a result of decades of basic research that lays the groundwork for the discoveries.

How has the funding landscape for your field changed in the last 5-10 years?
I have maintained pretty stable funding, but many researchers have not and as a result, morale is very low. Attendance at conferences has dropped; everyone is holding onto their money because they need it for salaries and supplies. The grant funding success rates are now extremely low because agencies have canceled competitions and there is a backlog of really talented people who are unfunded. Investments have been made to support new faculty positions and infrastructure at Canadian universities – we are ready to move forward, yet so many struggle to get a grant.

Congratulations on the Society for Molecular Biosciences award that you received recently – what led to this award?
I feel strongly about my commitment to teaching and training young scientists. Those who have trained with me have been highly successful in their careers, as well as in winning fellowships from the Natural Sciences and Engineering Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR) during their studies. The Grant and Moens Award for Excellence in Genetics was given in recognition of my contributions to genetics in Canada, both in the training of my students as well as the genetics research we carry out in my lab. I feel very honoured to be among this group of awardees, which includes SFU’s David Baillie, Professor Emeritus from my Department.

What sort of educational backgrounds and personal strengths do you look for in prospective group members?
In terms of education, they typically have a broad-based biology/biochemistry background. Academic strength is important, but that doesn't necessarily mean straight A students. Most importantly I look for people who are motivated and intellectually curious.   

What contemporary scientific issue concerns you most and needs more attention?
As a whole, we scientists are really awful at communicating what we do to the lay public. I try to teach students how to consider the audience and how to modify their communication accordingly, and how to distill knowledge in a way that is accessible to everyone.

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Read more: Dr. Verheyen’s profile on the Molecular Biology and Biochemistry website, the Verheyen lab site and the Featured Researchers page

Interview by Jacqueline Watson with Theresa Kitos