In 2023, members of Team Kili, led by Climb leader Luke Timmerman, raised more than $1.3 million for innovative research and compassionate care at Fred Hutchinson Cancer Center. We are deeply grateful for their dedication.
Together, this powerful community of climbers and their supporters are helping Fred Hutch make the discoveries that millions of people urgently need and move them from the lab to the clinic as quickly as possible. This report highlights just a few examples of the projects they help support through their contributions. We are grateful to Luke Timmerman for his leadership and extend our thanks to every member of this community for their passion and commitment to Fred Hutch’s mission. Step by step, we are improving and saving lives.
Bone marrow transplantation — an approach first developed at Fred Hutch — is considered one of the first types of immunotherapy. In the last several decades, it has transformed care for hundreds of thousands of patients, particularly those with blood cancers. Yet the approach walks a fine balance: It must unleash disease-fighting T cells to destroy cancer without causing cells to attack healthy tissue (a side effect called graft-vs.-host disease, or GVHD). Now, Geoff Hill, MD, a professor at Fred Hutch and UW Medicine who leads Fred Hutch's Translational Science and Therapuetics Division, and is scientific director of our Immunotherapy Integrated Research Center; postdoctoral researcher Simone Minnie, PhD; and members of the Hill Lab are exploring a new way to tip the balance.
The strategy, which has so far only been tested in mice, first used a specific treatment to clear away T cells most likely to attack healthy host cells. This left a subset of T cells that recognized the tumor but were unable to destroy it. Current scientific practice would suggest that these T cells had had their “brakes” applied by the tumor. Often, researchers will remove these brakes using an approach called immune checkpoint inhibition. In this case, however, the Hill group found that the T cells’ brakes weren’t on, they just needed to step on the gas, instead. Using a novel compound developed by Fred Hutch recruit Aaron Ring, MD, PhD, who holds the Anderson Family Endowed Chair for Immunotherapy, they activated the “gas pedals” on the T cells, enabling the cells to fight the tumor. Now, Drs. Hill and Minnie are working to understand these results and see if their success in mice will translate to patients.
Basic research is the basis of innovative treatments and approaches developed at Fred Hutch and beyond. Understanding how healthy cells function as they grow and divide can provide insights into how cancer cells hijack these processes — and lead to new and more precise treatments.
Basic scientist Lucas B. Sullivan, PhD, and his team are focusing on the humble mitochondrion, often called the “powerhouse of the cell.” Researchers have long known that mutations in mitochondria can introduce errors that drive some human cancers. But why would a mutation that damages a cancer cell’s ability to make power help it thrive?
Dr. Sullivan’s team discovered that, over time, cancer cells deficient in a key metabolic enzyme slowly began improving their ability to proliferate by creating more of a certain amino acid that encourages growth — essentially overcoming the mutation.
Then, the team discovered something even more surprising. Often, cells also responded to the first mitochondrial deficiency by inducing another deficiency. For some reason, having BOTH deficiencies actually allowed the cells to thrive. “It really highlights the complexity of metabolism, which makes it a beautiful but difficult process to study,” said Dr. Sullivan.
Now, the team will continue to learn more about this process, and how to target the byproducts of the two mutations. Ultimately, their goal is to advance approaches doctors can use to effectively suppress or disarm tumors.
Fred Hutch’s Global Oncology program includes a focus both on emerging diseases and on known threats, such as cancers, malaria, and HIV, that cause suffering worldwide. This work — always critical — is becoming more urgent than ever, as ecological disasters, pandemics and epidemics, and widespread inequality continue to stress health systems and challenge individuals and communities. The team’s findings unlock wide-ranging advances that can help to intercept disease, diagnose illness, and protect global communities.
For example, Leslie Goo, PhD, MPH, and her colleagues in Fred Hutch's Vaccine and Infectious Disease Division recently discovered a powerful antibody that appears to block all four strains of the mosquito-borne virus that causes dengue fever, a disease that sickens 100 million people every year. The team’s experiment was designed to identify potent immune proteins called broadly neutralizing antibodies (bNabs) that can block many strains of the dengue virus. Their study cohort was from Colombia, where repeated infections with multiple strains of dengue and Zika are common. This meant that participants’ immune systems were more likely to have evolved bNabs.
Dr. Goo and her team uncovered 23 new bNabs, including one that blocked infection by all four dengue strains and also neutralized Zika. Several of those antibodies appear better at blocking infection than the handful that have been previously identified by researchers.
These antibodies must still be tested against dengue and Zika infection in donated human blood — but these preliminary findings are exciting. They could open new opportunities for scientists searching for more effective vaccines and treatments for dengue and similar viruses.
In their community and actions, the Kili team demonstrated a commitment to cultivating diverse expertise and voices. Fred Hutch shares this commitment. Diversity, equity and inclusion are organizational priorities, and we recognize that achieving our goals is the work of our entire enterprise.
Part of this commitment is improving access to care for more people and ensuring that research responds to the needs of as many populations as possible. Burcu F. Darst, PhD, and her group from Fred Hutch’s Public Health Sciences Division are digging into the way scientists and doctors evaluate men’s risk of prostate cancer. Prostate cancer has the highest incidence rates among men with African ancestry. It is also the second-leading cause of cancer death in this group. Although these health disparities are linked to many social determinants of health and to systemic racism in medicine, prostate cancers also have a strong genetic association. This provides a targetable option for improvements in screening and early detection.
Polygenic risk scores, or PRS, incorporate genetic information that has been collected from large groups of people. By linking specific genetic variants to health outcomes, researchers can predict a person’s genetic risk for a disease. Although useful, an estimated 86% of the studies that have been used to develop PRS only include people of European heritage. Could this make the approach less effective for people from other backgrounds?
To explore this issue, Dr. Darst’s team began by creating a PRS using data from a larger and more diverse group of people. Next, they examined the efficacy of this new resource by using data sets from other, unrelated groups that included both genetic information and patient outcomes. They checked to see how well their resource would have predicted outcomes based on the risk information alone. Their findings validated the improved predictive ability of their PRS in men from diverse populations. Now, the team hopes to build on these findings to strengthen screening guidelines and continue to address disparities in prostate cancer.
Diversity, equity, and inclusion at Fred Hutch: Our commitment to diversity, equity and inclusion includes a goal to establish Fred Hutch as a national exemplar in academia for its core DEI approaches and practices. We know that the Timmerman Climb community shares these goals. We invite you to read more about our approaches and guiding principles.
Each summer, it is exciting to see our halls and labs filling with teachers and students. In addition to training graduate students and postdoctoral fellows and fostering faculty development, Fred Hutch engages and empowers young people with programs designed to pique their interest and help them launch careers in research and medicine. Our education programs place a strong focus on attracting students from a wide variety of backgrounds. They invite students in high school, college, and beyond to gain valuable experience at the lab bench, take part in internships, join data science programs, and more. We also offer a range of opportunities to inspire teachers and other educators and give them the support to help students build a strong foundation in — and love for — scientific discovery.