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Lisa Coussens: Cancer breakthroughs a ‘true testament’ to basic research

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Lisa Coussens

The start of 2019 came with news that deaths from cancer have dropped sharply in the past three decades.

Lisa Coussens wants to keep kicking the disease while it’s down.

Coussens has done pioneering work on what’s now a burgeoning body of cancer research: How to harness the body’s immune system as a tool against the disease. From her laboratory at Oregon Health and Science University in Portland, she studies how cancerous tissue interacts with the cells around it -- and why sometimes, a tumor can flip disease-fighting immune cells from foe to friend. She’s also the associate director for basic research at the university’s Knight Cancer Institute.

Coussens was one of 416 elected Fellows named in November – the latest in a series of awards in an academic career that had its unlikely roots in the art world. But by the time she started working on a PhD, “It was clear to me that I wanted to study some aspect of cancer,” she said.

Coussens said it has been “remarkably gratifying” to see the basic research move increasingly into the hands of physicians – “and a fabulous opportunity for the trainees that are coming up out the lab to think about basic mechanisms but also then to be able to apply those principles and hypotheses to the clinic to do what we all want to do and that is impact patients, hopefully.”

She plans to attend the AAAS Annual Meeting in February, where the new Fellows will be recognized.

 

How’s it feel to be named a fellow? What went through your mind when you got the news? 

It made me really proud of my lab, and our accomplishments and our contributions to the field. Being recognized by one’s peers is the ultimate honor … it’s heartwarming. But ultimately, all we want to do in science is make a difference. Accolades to laboratories like this really say “Good job, guys, your work has made difference, and we think differently now because of the work you have contributed.” That’s just all good, and certainly motivating for the trainees in the labs.

 

Your field has gotten a lot of attention lately. What do you think of the progress made against cancer, and where do you think the fight may be headed next?

With checkpoint inhibitors targeting just three molecules, we as a field have changed cancer medicine forever, for the better. The patients that respond are having better responses to these therapies than they have ever had before. And then if you add the therapeutics in with CAR-T for the hemo malignancies, it engenders remarkable optimism over the next few years to forever impact outcomes for patients with cancer.

In the solid tumor area, we’re targeting three “checkpoint molecules.” Those three represent only three in a family of modifiers of T-cell responses, where in clinical trials we’re looking at an expanded repertoire within the family.  Not all tumors respond to therapeutics targeting those three molecules, so our hope is that by understanding the biology of all of the other checkpoint proteins, we’ll be able to make an impact in the 70-80 percent of patients that aren’t responding thus far.

Basic discoveries coming out of labs like mine and all my colleagues’ lead to translation, to understand all of these other mechanisms and pathways that tumors use to shut down T-cell responses. I think it’s really a testament to the science. The impact that immune therapies are making is a true testament to the contribution of basic science.

 

What drew you to your work? Were you interested in science as a kid, or did that come later?

I went to college with the goal of pursuing a career in art. I had a small arts scholarship for my undergraduate. What became quickly apparent to me was that I was probably never going to be able to support myself as an artist. And my other passion in life had always been biology. I’d always taken science classes as a young person, and so my undergraduate work was in marine biology.

I was lucky, because I lived in the Bay Area, and Genentech had been born a few years prior. I got a job washing dishes in Genentech because I had a bachelor’s in biological sciences, and I washed dishes there for about six months. Then I got picked up as a technician in one of the world’s premier molecular biology labs with a scientist whose name was Axel Ullrich. He had done pivotal work as a post-doc and as a young scientist in cloning the human insulin genes and some other really notable early targets that revolutionized recombinant DNA methodologies.

As a technician in his lab, he taught me molecular biology. His lab focused on identifying the receptors for ligands like EGF, epidermal growth factor and NGF, nerve growth factors.

The projects he gave me in his lab were to clone cDNAs for those receptors, and I was really good at it, I guess. I was productive with the team I had in place in the lab … It was a very productive period and very good for Genentech at the time. I was there for eight years, and I recognized that if I didn’t pursue an advanced degree, I would be a technician forever. That didn’t sit well with me. So, I left Genentech and did a PhD at UCLA.

 

You’ve written that researchers should “embrace the biology of the tumor” and how it interacts with other cells. How is that advice being put into practice?

I think at this point in our evolution, that tumors are dysfunctional tissues is generally accepted as dogma. That certainly wasn’t the case when I started my career. My mentors have been pushing that concept for quite some time, but the experimental models weren’t in place to provide compelling data for the field to recognize the important contributions of microenvironment. With the advent of better tools and better models, you can’t argue that the microenvironment controls cancer development in addition to the genomic events that happen within neoplastic cells. It’s the combination of the two. This is broadly embraced at this time, and I think being nominated and then accepted as a AAAS Fellow is a testament to that. I think it’s the research that my laboratory has pushed from the beginning along with an entire community of labs like mine. This is what we have been doing.

 

What advice would you give someone considering a career in your field today?

Science is hard in all fields. Especially given that in academic science, we’re also burdened with writing grants and funding. What I say to trainees is that if this is your passion, then be true to yourself and pursue it, recognizing it’s going to be hard and there are easier ways to make a living. But if this is your passion, absolutely -- go for it. And be willing to be brave, recognizing that you’re not always going to be right and you have to have the personal fortitude to stick with it through hard times and adapt to what the data’s telling you. You can’t be stuck with dogma. You have to be willing to challenge it, so leaps can be made and fields can move forward.

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Matt Smith