Mapping out a better way to treat colon cancer

Q & A with Cancer Research Institute of Northern Alberta member Kristi Baker

ROSS NEITZ - 3 May 2019

Kristi Baker is a rising star in the field of colon cancer research. An assistant professor of oncology, and a member of both the Cancer Research Institute of Northern Alberta (CRINA) and the Women and Children's Health Research Institute (WCHRI), Baker and her team are working to open new avenues of treatment for people diagnosed with colon cancer.


Baker's lab studies the association between the failure of a cancer cell to maintain healthy DNA and how easily it can be detected by the immune system. Their aim is to gain a better understanding of why the immune system is blind to most colorectal cancer cells and to develop new treatments that can boost natural cancer detection without harming healthy cells.


Q: What brought you to the U of A and what has been your career trajectory?


I've been here four years as of April 1st. I'm originally from the Montreal area and I did my graduate studies in a lab in the pathology department at McGill. I was studying colon cancer with my supervisor who was very interested in a particular subset of colon cancer called "MSI" that happens to have a really good immune response associated with it. But nobody really knew why that was or what it meant for the patient. So I really became intrigued by this and wanted to learn more about what happens in the intestine in terms of the immune system, because it turns out the intestine has a very specialized immune system.


In 2008, I decided to do my postdoc at Harvard with Rick Blumberg, an expert in the specialized intestinal immune system. I spent my postdoc years studying inflammatory bowel disease and the processes by which inflammation and immune responses are really activated in the intestine. I went to Boston not having any intentions of doing cancer research but my project at some point naturally turned in that direction.


I was also fortunate in that my specific project in Boston was looking at how antibodies regulate immune responses in the intestine. This ended up being really fortuitous because just as I was leaving Boston and starting up my own lab here at U of A, it was found that the MSI colon cancer I'm interested in is the only one that responds to new antibody-based immunotherapies called "checkpoint inhibitors". So it turns out I have this niche expertise where I've learned both about the immune biology of the intestine and how antibodies, such as those in the new immunotherapies, control this.


Q: What's the focus of your lab now?


I'm trying to bring all of what I've learned together and study what lets colon cancers grow in the intestine in the first place. Why is the immune system not detecting them? Also, in patients with MSI cancer, why is it naturally being detected better than in others and responding to immune therapies? We hope that by answering these questions we'll be able to figure out new therapies that we can use to treat a greater number of patients with colon cancer.


The MSI colon cancers that I study makes up only about 15 per cent of colon cancers. About 85 per cent of colon cancers are not responding to these new therapies and still have a pretty dismal prognosis. So by studying one type of cancer that responds well to immunotherapy, I'm trying to learn how to train a patient's own immune system to be able to better target the tumour.


Q: What was exciting about the opportunity at the U of A?


I always wanted to come back to Canada. That was always my intention. I also love doing research. It gets me up in the morning. But I also find it really enriching to instruct, develop and work with trainees. The position at the U of A really gave me the opportunity to do it all.


In addition to the research that I do, I teach a cancer biology class. The opportunity really gave me the chance to build this class from the ground up which is targeted towards second year undergraduates. So the nice thing is that they've taken all these prerequisite courses in their first year. In their brain there's one box that's cell biology and one box that's genetics and one box that's metabolism. And with cancer it integrates that and brings it all together. So it's a really good platform for integrating the pieces of knowledge that you're exposed to as an undergrad and I think it's a really unique opportunity to be able to teach these students-because everybody's life is touched by cancer in some way or another. It's relevant in everybody's life.


In addition to that opportunity, the facilities here and the programs are really great. I'm very fortunate that I work with a number of colleagues who have a lot of expertise. One of the things that defines MSI cancer is that it's very prone to mutations because it doesn't take care of its DNA very well. It turns out that the group I work with at the Cross Cancer Institute in the oncology department are specialized in this DNA maintenance. So I have a huge body of expertise here that I can tap into as I need it.


Q: Why is it important for you to share your work with others?


I really enjoy interacting with people and getting them to think about cancers in a way that they can understand. My family asks all the time, 'Why haven't you cured cancer yet?' And the answer is because it's really hard. I wish I had cured cancer by now. I have two grandparents who have died of cancer and I really wish that we had a cure. We don't, and it really takes a lot of time to get there. But I find that if you sit down and have a conversation with people about this, they really can get it. They might not understand the details, but they certainly can understand the concepts that you're talking about. I really enjoy seeing that light come on for people.


Q: How does your affiliation with the Cancer Research Institute of Northern Alberta (CRINA) help further your work?


Cancer research touches so many disciplines. I'm part of the oncology department at the U of A that consists of about 20 professors and we're labeled as the oncology research group. But there are so many people who are doing work related to oncology scattered throughout the university.


Having an organization like CRINA makes us visible to each other and creates a network where we can lean on each other if we run into a problem and need expertise. As an example, I got a phone call one day from a person in the biomedical engineering department asking how silver nanoparticles could be targeted specifically toward a tumour. We ended up having an hour long conversation about our research and how we could work together and share knowledge. CRINA facilitates that collaboration because it makes us very visible to each other.


Q: What's next in your research?


We're really trying to understand how MSI cancer is interfacing with the immune system. Once we know that, we want to use what we've learned as a training set for other cancers. Once we get a sense of what cells are being activated by MSI cancer and how it's activating them, we want to figure out how can we activate similar populations of cells in the rest of the colon cancers.


Everybody wants to see a cure for cancer, but we're not going to get there unless we're getting the funding for the basic research that underlies all of our work. Basic science helps us build the foundation for what will be the next wave of therapies and that work takes a long time. We know it's slow, but we're trying to be safe and we're trying to be correct.