Gray Foundation

A distinct mission of the Gray Foundation is to accelerate research, improve treatment, and raise awareness for people who have inherited mutations in the tumor-suppressing BRCA1 and BRCA2 genes. These mutations increase the risks of breast, ovarian, pancreatic, and prostate cancers and can both be inherited and arise sporadically. Since 2019, the foundation has awarded more than $8.3 million in grants to Harvard Medical School faculty members supporting several projects to prevent breast cancer development by facilitating early detection and treatment of people who carry these mutations.

Buoyed by the foundation’s support, Joan Brugge, PhD, the Louise Foote Pfeiffer Professor of Cell Biology in the Blavatnik Institute at HMS, and colleagues from the School, its affiliate hospitals, and other labs around the world have used various technologies to investigate the minute changes that take place within cells on the road from health to tumor formation. In one project, they employed samples derived from human breast tissue; in a subsequent project, they began testing the hypotheses generated from these human studies by using mouse models, which can provide invaluable experimental approaches for identifying and achieving control of the steps involved in tumor formation—and can do so faster than studies in humans.

“Our findings have provided evidence of alterations that accumulate in breast tissues in association with aging and BRCA1 and BRCA2 mutations,” says Brugge, who is also co-director of the Ludwig Center at Harvard. “However, the number of samples that were examined in our previous work was too small to distinguish which factors associated with aging and BRCA1/2 mutations contribute to cancer initiation.”

Thankfully, the Gray Foundation, which has given over $160 million to leading research institutions for the treatment and prevention of BRCA-related cancers, recently pledged to support a larger collaboration, co-led by Brugge. “With this new funding, we will be able to not only collect a greater number of breast tissues, but also carry out deeper and broader analyses to better understand the nature of changes with age and high-risk mutations,” says Brugge, “in order to generate hypotheses about tumor initiation and strategies to prevent tumorigenesis.”

Dana Zucker, MBA ’95, chief executive officer of the Gray Foundation, praised Brugge for her steadfast dedication to BRCA research.

“Dr. Brugge is an impactful researcher who has committed her energy to answering key provocative questions for the BRCA field, particularly by focusing on early events that predispose BRCA mutation carriers to cancer,” Zucker says. “Her rigor, creativity, and resourcefulness have resulted in progress that the Gray Foundation wishes to catalyze further.”

The foundation also recently awarded grants to support two projects led by collaborators Peter Sorger, AB ’83, PhD, the Otto Krayer Professor of Systems Pharmacology in the Blavatnik Institute at HMS, and Sandro Santagata, MD, PhD, an HMS associate professor of pathology at Brigham and Women’s Hospital and an associate professor of systems biology in the Blavatnik Institute at HMS. Sorger and Santagata work closely together in the HMS Laboratory of Systems Pharmacology to develop new single cell imaging methods to advance precision cancer care. In one project, Sorger and Santagata are working to develop and maintain a shared electronic resource and data portal in support of the Gray Foundation’s research into early detection, prevention, and treatment of BRCA1/2-associated cancers.

“We anticipate that the Gray Foundation BRCA Atlas Data Portal will become a centerpiece of the foundation’s cancer program, helping to accelerate research, attract new collaborators and trainees, and increase clinical impact,” Sorger says.

In the second project, Sorger and Santagata are teaming up with Ronny Drapkin, MD, PhD, director of gynecologic cancer research at the Basser Center for BRCA at the University of Pennsylvania Perelman School of Medicine, to use tissue imaging methods developed at HMS to study the earliest stages of serous ovarian cancer in patients with BRCA mutations. The group aims to precisely define the composition, state, and spatial organization of the tumor-immune microenvironment.

This team-science approach is a tenet of the Gray Foundation, which believes that the best minds should be linked and synchronized to solve some of the most challenging biomedical problems, particularly the predisposition to cancer for BRCA carriers and how to prevent or intercept the development of cancer. “No lab on its own could provide the holistic view that is needed to advance the field of BRCA research,” Zucker says.

Sadly, one integral Gray Foundation-supported BRCA research team member died unexpectedly in October 2021. David Livingston, AB ’61, MD, was Brugge’s esteemed project partner at Dana-Farber Cancer Institute. In addition to being a valued mentor to myriad students and junior scientists, Livingston was a prominent expert on the molecular origins of breast and ovarian cancer. His work had been the cornerstone of many studies of cancer susceptibility linked to BRCA function and mutations. By understanding the tumor-suppressive properties of BRCA1 and BRCA2, he paved the way for studying novel approaches to breast and ovarian cancer prevention.

“David’s relentless energy and contributions to the BRCA field were legendary,” says Gray Foundation founders Jon and Mindy Gray. “While we will never be able to replace his presence, we are honored to help build on his legacy of mentorship, scholarly research, and collaboration through the endowment of the David M. Livingston Chair at Dana-Farber Cancer Institute.”