Breast cancer researcher Dr. Nancy E. Davidson, senior vice president and director of the Clinical Research Division at Fred Hutchinson Cancer Research Center, has received the Jill Rose Award from the Breast Cancer Research Foundation. She accepted the honor of Oct. 19 at a BCRF symposium and fundraising luncheon in New York City.
The Jill Rose Award, established in 1996, was named in honor of a founding BCRF advisory board member and philanthropist who, according to the foundation, “was a dynamic advocate of institutions seeking to dispel the mysteries surrounding breast cancer.”
“It was such an honor to receive the Jill Rose award,” Davidson said. “It allowed me to publicly thank the BCRF and my many colleagues for their support and partnership in the quest to eliminate breast cancer. I am also grateful to the many patients who have trusted me to provide their care. They have taught me so much and I can only hope that I have given back to them. I dedicated my Jill Rose award to all of them.”
Davidson, a member of the BCRF Scientific Advisory Board, has published key findings on the role of hormones, particularly estrogen, on gene expression and cell growth in breast cancer. She has led several important national clinical trials of new treatments for breast cancer, including chemo-endocrine therapy for premenopausal women with the disease.
Since 1998, Davidson has received nearly $5 million in BCRF funding. Her current BCRF-supported research, which she is conducting in collaboration with Drs. Kevin Cheung, Cyrus Ghajar, and Taran Gujral at Fred Hutch, includes seeking to identify new targets to prevent late recurrence of hormone-positive breast cancers, as well as laboratory studies to develop ways to sensitize “sleeping,” or dormant, breast cancer cells to chemotherapies. The goal of this work, she said, is to develop more effective combination therapies to kill dormant tumor cells and micrometastases to prevent breast cancer from spreading. (Micrometastasis is when cancer spreads from its original location to other sites in the body, but the new tumors are too miniscule to be clinically detected.)
The luncheon broke a BCRF record by raising nearly $2.5 million for the foundation, which since 2001 has provided more than $3 million in breast cancer research grants and awards to Fred Hutch. This year alone, the organization has invested a record $59.5 million in new awards to more than 275 investigators from 15 countries.
Past recipients of the Jill Rose Award include University of Washington breast cancer geneticist Dr. Mary Claire King, angiogenesis researcher Dr. Judah Folkman of Harvard, and Dr. Harold Varmus, Nobel laureate and former director of the National Cancer Institute.
In addition to her appointment at Fred Hutch, where she holds the Endowed Chair for Breast Cancer Research, Davidson is president and executive director of Seattle Cancer Care Alliance, Fred Hutch’s clinical care partner; and she is head of the Division of Medical Oncology at the University of Washington School of Medicine.
She has been a member of the Hutch faculty since Dec. 1, 2016. Prior to her arrival in Seattle, she served from 2009–2016 as Hillman Professor of Medicine and associate vice chancellor for cancer research at the University of Pittsburgh and director of the University of Pittsburgh Cancer Institute.
— Kristen Woodward / Fred Hutch News Service
Researchers at Fred Hutchinson Cancer Research Center have identified a specific subset of blood-forming stem cells that is exclusively responsible for repopulating the bone marrow after autologous transplantation with the patient’s own cells.
The discovery, published Nov. 1 in Science Translational Medicine, provides a better target population of cells that could be used for a variety of therapies for blood cancers, blood disorders and to deliver gene therapies for infectious diseases such as HIV or genetic disorders such as hemoglobinopathies.
“These findings came as a surprise; we had thought that there were multiple types of blood stem cells that take on different roles in rebuilding a blood and immune system,” said senior author Dr. Hans-Peter Kiem, Endowed Chair for Cell and Gene Therapy and director of the Stem Cell and Gene Therapy Program at Fred Hutch.
“This population does it all,” he said.
Blood stem cells are the building blocks of healthy bodies. They are the workhorses of bone marrow transplant, replacing diseased blood cells with healthy blood stem cells that grow and proliferate into all the cells —T cells, B cells, platelets and more — that constitute a healthy blood and immune system.
“The gold standard target-cell population for stem cell gene therapy are cells with the marker CD34,” said lead author Dr. Stefan Radtke, a research associate in the Kiem Lab at Fred Hutch. “But we used two additional markers to further distinguish the population from the other blood stem cells.”
Tracking hundreds of thousands of cells in the blood, the Fred Hutch team found that the specific stem cell group — marked as CD34+CD45RA-CD90+ — started rebuilding all different cells of the blood and immune system within 10 days of being infused in nonhuman primates undergoing transplant. A year later, the researchers found strong molecular traces of those cells, indicating that the cells were responsible for the ongoing maintenance of the newly transplanted system.
The specialized subpopulation represents about 5 percent of all blood stem cells in the preclinical model used in the study.
“Our ability to track individual blood cells that developed after transplant was critical to demonstrating that these really are stem cells,” said co-author Dr. Jennifer Adair, assistant member of the Clinical Research Division at Fred Hutch.
After the researchers performed the study in a preclinical model, they confirmed their findings using human cells and are now working to move their findings into the clinic with hopes to be ready to integrate them in ongoing clinical trials. The researchers are currently looking for commercial partners.
Kiem, Radtke and Adair are co-inventors on patents related to this research. Because scientists at Fred Hutch played a role in developing the discoveries in this study, Fred Hutch and certain of its scientists could benefit financially from this work in the future.
The National Institutes of Health, Fred Hutch and the Cuyamaca Foundation funded the research.
— Molly McElroy | Fred Hutch News Service
Most cancer deaths happen because the cancer has spread to distant sites throughout the body — a phenomenon called metastasis. Why does metastasis occur, and how can we stop it?
With new grant funding and cutting-edge technology, a collaborative group of Fred Hutchinson Cancer Research Center investigators aims to help answer these big questions in the context of the skin cancer melanoma.
The team’s project focuses on immune cells called macrophages, which their work has shown — counterintuitively — help tumors become metastatic.
“This means that our own immune cells, instead of protecting us against diseases, promote cancer. If we can better understand why and how macrophages turn against us, we might be able to identify new therapeutic targets for the most deadly forms of cancer,” said immunologist and project leader Dr. Anthony Rongvaux.
A collaboration between Rongvaux, Dr. Jason Bielas, and Dr. Raphael Gottardo, the research is funded through a competitive grant program sponsored by the Hutch’s Immunotherapy Integrated Research Center, or IIRC, and supported by the Bezos family Immunotherapy Initiative. The project is a continuation and expansion of exploratory work the team conducted earlier this year with a first round of funding from the IIRC.
The goal of the grant program is to support immuno-oncology projects at the Hutch to use a new technology called single-cell RNA sequencing, which allows researchers to tell apart different types of cells in a mixture and analyze patterns of gene activation in thousands of individual cells at once. Bielas is working with the company 10x Genomics to develop this single-cell RNA sequencing technology platform, and this grant program helps to cement the Hutch’s position as an early adopter.
Rongvaux’s team was one of five at the Hutch that was awarded a $25,000 exploratory grant for a single-cell RNA sequencing project in March, but the only one of the five that was awarded a follow-up grant of $100,000 this fall to continue their project.
With the second round of funding, the team is following up on its results so far to better understand how tumor-associated macrophages develop and function using the molecular information they have been able to glean with the help of this new technology.
“Our original hypothesis was that a specific population of macrophages is responsible for tumor support. Single-cell RNA sequencing allowed us to characterize these cells with unprecedented resolution,” Rongvaux said. “And indeed, we found that tumor-infiltrating macrophages present a really unique molecular profile, which isn’t found in macrophages from healthy tissues.”
The collaborative nature of the project is key, Rongvaux said.
“Jason is a pioneer of this technology, and his expertise is invaluable for the design, analysis and interpretation of the experiments,” he said. “This new technology generates a new type of data at very large scale. Analyzing these data relies on sophisticated algorithms, developed and used by Raphael and his group. This combination of cutting-edge technologies and a close collaboration between our three labs is indispensable to achieve our research goals.”
— Susan Keown / Fred Hutch News Service
Lymphoma physician-scientist Dr. Oliver Press of Fred Hutchinson Cancer Research Center was honored posthumously Oct. 28 with the John Ultmann Award for contributions to lymphoma research. The researcher’s brother, Dr. Michael F. Press, and widow and research collaborator Nancy Press accepted the award on Press’ behalf at an annual meeting of professionals working in the lymphoma and myeloma fields.
Press made major contributions throughout his career to the development of targeted cancer therapies for lymphoma and other types of blood cancer. His work centered on therapies based on antibodies, disease-targeting proteins produced by immune cells. These included antibody-guided radiation, a strategy that has been translated into commercial therapeutics, and a type of genetically engineered immune cell therapy (or CAR T-cell therapy) that is making its first-in-human debut this fall. At the time of his death in September of the brain cancer glioma, Press held the David and Patricia Giuliani/Oliver Press Endowed Chair in Cancer Research at Fred Hutch.
The award is named after lymphoma research giant Dr. John Ultmann, a former director of the University of Chicago Cancer Research Center who was best known for his work to develop staging and staging-guided treatment for Hodgkin lymphoma. The honor is presented yearly by the SASS Foundation for Medical Research, the Center for Lymphoma and Myeloma at Weill Cornell Medicine, and Imedex LLC.
This award presentation “brings with it one crying and one smiling eye,” Ultmann’s widow, Ruth Ultmann, said at the ceremony. “The crying eye is for Dr. Oliver Press … The smiling eye is for the enduring legacy that he leaves behind. He, like my husband, John, contributed greatly to the understanding and the treatment of lymphoma, with an enormous impact in science, medicine and the lives of many individuals. Dr. Press taught, trained and mentored the next generation, who will continue to advance research on the treatment of lymphoma.”
Dr. Morton Coleman, a blood cancer specialist at New York-Presbyterian Hospital Weill Cornell Medical Center, presented the award to Nancy and Michael Press. The award presentation followed a talk by Press’ colleague, Dr. David Maloney of Fred Hutch, on the late scientist’s life and impact on the development of cancer immunotherapies. Maloney also delivered the Ultmann Lecture in Press’ stead, focusing on the latest developments in CAR T-cell therapy for lymphoma and chronic lymphocytic leukemia.
Since 2008, the Ultmann Award has been bestowed on many greats in the field, including, most recently, Dr. Elaine Jaffe of the National Cancer Institute, Dr. Volker Diehl of the University of Cologne in Germany, and Randy Gascoyne of the British Columbia Cancer Agency. This year is the first time the award has been given to a scientist in the Fred Hutch/University of Washington Cancer Consortium.
— Susan Keown / Fred Hutch News Service with reporting from Nancy Press