For Geoffrey M. Wahl, Ph.D., a former Komen scholar, helping others who face serious diseases has been a passion ever since he battled an aggressive viral encephalitis as a child.
Now a world-renowned investigator in breast cancer genetics, disease progression and research methodology, Dr. Wahl received the 2022 Brinker Award for Scientific Distinction in Basic Science for his significant contributions to the field of cancer genetics, including the mechanisms of drug resistance and genome stability.
Dr. Wahl’s work at the Salk Institute for Biological Studies Gene Expression Laboratory in La Jolla, California, has significantly advanced the understanding of mammary cell development, which paved the way for future discoveries in breast cancer research and treatment.
“I’m truly standing on the shoulders of giants who have received the Brinker Award before me — people who I’ve revered my entire career,” Dr. Wahl said. “For me to be included in that group now is humbling. Importantly, I see this award as a recognition of the incredible work that my mentees have done. I hope this award will show them that their hard work has generated results and insights held in the highest esteem by the community.”
A Passion for Helping Others
Dr. Wahl remembers his time in the hospital as a child — and the boy in the bed next to him who passed away of the same illness — as the catalyst that inspired him to pursue science. When a close friend’s uncle was diagnosed with leukemia, Dr. Wahl decided to pursue topics related to cancer. He chose not to be a physician as his childhood experience in the hospital made him squeamish about blood.
During his postdoctoral research at Stanford University, Dr. Wahl met his wife, Barbara, then a medical student. When Barbara pursued breast oncology as a career path, they would frequently discuss the barriers in knowledge that limited her options for diagnosis and treatment. When he met breast cancer survivor Bianca Lundien Kennedy, Dr. Wahl was inspired to focus his research efforts more specifically on how breast cancers arise and progress.
“Bianca’s sister had breast cancer four times. After hearing her story, I knew we had to do something to help Bianca and her sister understand their cancers better,” Dr. Wahl said. “I wanted to use the knowledge that my lab and others had gained to try to understand how these very complicated breast cancers arise, recur and progress.”
Dr. Wahl invited Bianca to be a patient advocate at the Salk Institute and redoubled his groundbreaking cancer research to concentrate on breast cancer. For more than a decade, he has focused on ensuring his work has direct relevance to patients and improving outcomes.
“The problem we focused on has concerned how the incredible complexity of cells within any given patient’s cancer arises,” Dr. Wahl said. “We are especially interested in patients with triple-negative breast cancer. These patients’ cancers often present very early on with a mutation in a gene called P53, which we had studied for decades.”
Dr. Wahl explained the P53 gene has been called “the guardian of the genome” because it is a tumor suppressor that prevents cells from growing if they experience any genetic damage or are placed under a variety of stresses. However, when P53 is mutated, cells can grow even under unfavorable conditions, such as during the early stage of triple-negative breast cancer development, especially in patients who inherit one of the BRCA genes and may have acquired some damage to their genetic information.
While the Brinker Award acknowledges Dr. Wahl’s early work in discovering how the P53 gene functions, the award also acknowledges his breakthrough discovery that a P53 gene mutation reprograms adult mammary cells to a very primitive state.
“This process of reprogramming is very important for cancer progression to occur because the cells are reprising an early developmental state that’s never found in the adult,” Dr. Wahl explained. “We think this is going to offer many new targets for therapy. We can imagine those proteins that are expressed on the cell surface to be especially attractive for the many new kinds of immune therapy that are resulting from the rapid advances in that field.”
Dr. Wahl’s cutting-edge work on developing gene signatures for cells from early embryogenesis through adulthood contributed to significantly advancing the field’s understanding of how the breast develops and how these programs are reprised in cancer. His research may make it possible to distinguish the cells generated early on in cancer development that are most likely to progress to malignancy.
“If we could only treat those people whose cancers, upon detection, are likely to give problems later on and treat them aggressively, while allowing other people who don’t have an aggressive cancer to be watched carefully to make sure their disease doesn’t progress, that would save a lot of people from a lot of anguish,” he explained.
Challenges to Advancing Research
Dr. Wahl has conquered many hurdles in his career, and he noted receiving funding for research as an ongoing challenge, especially for new ideas that “go against the grain.” When pursuing those new ideas, researchers must clear higher bars and rule out many alternatives that may be considered more likely based on traditional ideas, which makes the very nature of research a painstakingly slow process, he explained.
“Your mentees must have the patience, the perseverance and the gumption to do the experiments multiple times, in different ways, using approaches that make different assumptions to generate data that are absolutely bulletproof and reproducible,” Dr. Wahl said. “While we always try to make an interpretation that is correct, even if we are wrong, we are comforted by the knowledge that as long as our data are sound and reproducible, our efforts will move the field forward.”
Researchers must also not be afraid to challenge dogma when developing alternative explanations to critical questions, which can also lead to funding challenges, Dr. Wahl said.
“I find that fewer and fewer people are going into scientific research,” Dr. Wahl said. “This is related to the length of time to get a Ph.D. and complete postdoctoral fellowships. This combined with wages that do not compensate people adequately for the essential research that they are doing lead them to other career choices in which they may be compensated better for the effort they expend.”
Dr. Wahl identified the lack of national consideration for predictable funding at levels appropriate for the training and expertise of scientific trainees as an existential threat to breast cancer research.
Looking to emerging areas in the field that still need more research to truly advance the field, Dr. Wahl believes there is great promise in early detection, particularly in new technologies that can identify the early lesions most likely to become metastatic.
“When you detect cancers earlier, you don’t have the cellular complexity that defeats effective treatment later on,” Dr. Wahl said. “Early detection alone isn’t enough. It has to be wise detection. We have to know who to watch, who to treat and what types of therapeutic approaches will provide the best outcome with the fewest side effects.”
In reflecting on the Brinker Award and achievements in his career, Dr. Wahl is indebted to his wife, Barbara, and the strong partnership they have shared during their respective careers in medicine.
“We have called it a marriage of medicine and science,” Dr. Wahl said. “Barbara has been an important source of inspiration and knowledge in informing me of what patients go through when they are in various treatments for cancer.”
Dr. Wahl is also grateful to his longtime patient advocate Bianca, who has become a dear friend since joining his lab more than a decade ago and remains a critical partner in advancing his work.
“She has been an inspiration to our lab and our partner in disseminating the information in ways that will be understandable to the public,” Dr. Wahl said. “Very few scientists appreciate the power of having a patient advocate. She has inspired every trainee and technician in my lab.”
Dr. Wahl also expressed his gratitude to the dedicated students and postdoctoral researchers he has been privileged to mentor over the years throughout his career, as well as his many collaborators “who have made science so fun and fulfilling.”