An Early Love of Nature’s Biodiversity Leads to a Career in Cancer Research for Lisa Coussens, PhD
Lisa Coussens, PhD
Founded in 1887, the Oregon Health Sciences University (OHSU) is located in Portland, Oregon, and is home to the cutting-edge Coussens Lab, which focuses on the role of immune cells and their mediators as critical regulators of cancer development. The lab’s eponymous Director, Lisa Coussens, PhD, was born in Eureka, a small town in northern California into a middle-class family.
“My father had broken his back when I was a young child, and even though he worked his entire life, my mother was the family’s breadwinner,” commented Dr. Coussens. “I was strongly influenced by the women in my family, my mother being the youngest of 12 with 9 sisters. My grandmother was the matriarch of a female-dominated family, where we gave each other a lot of support.”
The Outdoors and a Chemistry Set
When Asked if she had an early interest in science that might have sparked her later desire to pursue a career in research, Dr. Coussens replied: “I grew up with a keen interest in the outdoors, the ocean, and all of my various biologic surroundings. My dad always encouraged trips out to the ocean, where I spent significant time exploring tidal pools, fishing with my dad, and just soaking up nature. It was a great way to grow up.”
About being inspired at an early age, Dr. Coussens continued: “I had a fabulous sixth-grade teacher, Clare Johnson, who had a science center at the front of the classroom, where she introduced us to chemistry and biology—it was captivating and triggered a keen interest in natural science. That was furthered in high school biology where my teacher, Mr. Summer invited students to grow and experiment with plants on his local farm. My interests in science were complimented by interests in art, particularly sculpture. I was awarded a local art scholarship and thus started college at San Francisco State University in 1976 as an art major, but quickly came to realize that making a living as an artist was unlikely, so I turned back to biology and never swayed from that path.”
Washing Dishes at Genentech
Dr. Coussens earned a BA in marine biology in 1980, but found it difficult to find work in her field. Fortuitously, the emerging biotech industry in the San Francisco Bay Area provided opportunity. “My first job out of college was at Genentech, Inc, in their glassware and buffer kitchens where I worked for 6 months. With my BA in marine biology, I was promoted to a technician, and I harvested oocytes from -Xenopus frogs to assay interferon clones. The emergence of biotech service companies selling assay kits ended the need for oocytes.
As luck would have it, my position was moved to Dr. Axel Ullrich’s laboratory. The lab was pushing the envelope with cDNA cloning of growth factors and their receptor. We cloned EGFR, HER2, c-KIT, and other receptor tyrosine kinases. It was a remarkable place to work, filled with bright, passionate colleagues. I was bitten by the research bug. We worked around the clock, and I missed a lot of holidays with my family but was happy to do so because the work was so thrilling. I didn’t appreciate the full implications of the research at the time, but I knew that if Axel was right, our research could potentially impact the lives of people with cancer. And he was right.” Earlier this year, Dr. Ullrich was awarded a Lasker Prize for his part in the development of trastuzumab.
Growing Pains and Collaborating With Mentors
Despite the growing excitement at Genentech, Dr. Coussens wanted more than being a technician in someone else’s lab. In 1988, along with her partner, she moved to Los Angeles, where she earned her PhD in biological chemistry at the University of California, Los Angeles, studying signal transduction pathways.
“Once again, I had several spectacular mentors, Drs. Harvey Herschman and Judith Gasson, who had a passion for education and mentoring. They were influential in helping me merge my bench and theoretic knowledge. When I finished my PhD, the utility of transgenic mouse models of human cancer captivated me; so, I applied for a postdoctoral position in 1993 to Dr. Doug Hanahan’s lab at the University of California, San Francisco (UCSF), as he was pioneering the use of transgenic models to study cancer development.”
“Doug had just developed a mouse model using human papillomavirus (HPV) oncoproteins, but it had not been fully characterized, so I took it on. I really didn’t know anything about pathology or how to use mice, so I spent a year teaching myself epidermal pathology and characterizing histopathologic changes as the mice developed cancers. It was an experience that had a profound effect on me.”
Mentoring is critical, and I think many scientists fail to appreciate that while their research may impact understanding of a problem, their main legacy will be in the next generation of scientists they train and impact.— Lisa Coussens, PhD
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Dr. Coussens’ postdoctoral research fueled her interest in tumor development and rational targeting for therapy. “What fascinated me in the transgenic mouse model of cancer was that the tissues became inundated with various flavors of leukocytes before cancer was apparent. Having no background in immunology, I sought out mentors at UCSF who could help me investigate what they were doing; there I met Dr. Zena Werb, who got me thinking about the biology of immune cells and how they might participate in cancer development. It was a remarkably powerful and productive time because several of our early collaborative papers served as a foundation for current thinking on the protumor role of immune cells and supported the hypothesis that therapeutically targeting inflammation could significantly impact cancer progression.”
Another Career Move
In 1999, Dr. Coussens was recruited to the UCSF Cancer Center by Frank McCormick, PhD, when he became the center’s Director. “My independent research program was geared toward dissecting inflammatory pathways to identify therapeutically actionable vulnerabilities in cancer development. And from that, we recognized that macrophages were not only profoundly important protumorigenic drivers, but also important factors in T-cell suppression.”
Dr. Coussens progressed through the ranks at UCSF, becoming a tenured Full Professor in Pathology. “With many stellar postdoctoral fellows in my lab, we were remarkably successful and produced several paradigm-shifting papers that have now participated in fueling emerging therapies targeting myeloid cells in tumors to quell their protumorigenic activities, in parallel with blocking their T cell–suppressive functions. After I turned 50, I began thinking about how I could have a broader impact than just on the research within my own laboratory.”
Brian Druker, PhD, Director of the OHSU Knight Cancer Institute, asked Dr. Coussens whether she would be interested in building a cancer biology program at OHSU. “He was looking for a basic science program with translational implications, which was exciting to me based on my own desires to translate research discoveries from my own laboratory. I accepted Brian’s offer, and in 2011, my laboratory and I moved to Oregon, where I became the Hildegard Lamfrom Endowed Chair in Basic Research, Chairwoman of the Cell, Development and Cancer Biology (CDCB) Department, and Associate Director for Basis Research in the Knight Cancer Institute. Thus far, we have recruited 15 faculty into CDCB, mostly junior but also some senior faculty, to stand as the cornerstone of basic science focused on the tumor microenvironment in the Knight Cancer Institute.”
Mentoring Is Essential
Dr. Coussens still runs her lab, but she’s hired more senior people to help with guiding postdoctoral researchers and students in the lab. “I’ve had to learn a new management style in running my lab, based on how time-consuming building a new department has been, as well as then learning how to mentor and equip new faculty so that they are successful and can realize their dreams and research goals. Institutionally, we are committed to developing new strategies for early detection of cancer, as well as precision oncology approaches that include therapies targeting the tumor microenvironment, and incorporating prospective in situ assays to monitor response and resistance in patients.”
Dr. Coussens shared a closing thought: “Mentoring is critical, and I think many scientists fail to appreciate that while their research may impact understanding of a problem, their main legacy will be in the next generation of scientists they train and impact. Our job is to create an environment that enables other people to make their dreams in this incredible field come true, too. We should encourage our mentees to be brave and bold in their scientific pursuits. Science is a gift, and it needs to be promoted and nurtured.” ■
DISCLOSURE: Dr. Coussens is a paid consultant for Cell Signaling Technologies; has received reagent support from Plexxikon, Acerta Pharma, Cell Signaling Technologies, and NanoString Technologies; and is an advisory board member for Syndax Pharmaceuticals, Carisma Therapeutics, Verseau Therapeutics, Zymeworks, and Cytomix Therapeutics.