Daniel A. Haber, MD, PhD
Director, Massachusetts General Hospital Cancer Center
Kurt J. Isselbacher Professor of Oncology
Harvard Medical School
Investigator, Howard Hughes Medical Institute
Massachusetts General Hospital
To understand how circulating tumor cells in the blood of breast cancer patients give rise to metastases.
Metastasis is the primary cause of breast cancer deaths, but how metastatic tumors develop is not well understood. Dr. Haber and his team study rare tumor cells, called circulating tumor cells (CTCs), that escape from the primary cancer and travel in the bloodstream to distant organs. There, they can grow and develop metastases. Dr. Haber’s lab bioengineered microfluidic devices, which isolate CTCs from patients’ blood, and the team is currently growing these cells in the laboratory to learn more about them, and consequently learn more about the metastatic process. Dr. Haber’s ultimate goal is to identify therapeutic strategies to target CTCs and stop the metastatic spread of cancer cells from early breast cancers, as well as prevent the further spread of breast cancer that has already metastasized.
While the majority of breast cancer cells do not survive in circulation—the bloodstream is a harsh environment for tumor cells—there is much to learn from those that do survive. Dr. Haber and his team are working to discover which genes make these cells so aggressive and figure out how to target them therapeutically. For example, by analyzing CTCs from breast cancer patients with existing brain metastases, they found that CTCs activated HIF1A, an important pathway for cells that need to adapt to lower levels of oxygen. This pathway was also uniquely amplified in brain metastases (not in original breast tumors), suggesting that therapies targeting HIF1A may be helpful in these patients.
The team’s ongoing work is now focused on understanding how advanced breast cancer cells adapt to stress during metastasis. When cancer cells divide rapidly, they can make mistakes—a process called replication stress—that would typically result in cell death. Through analysis of CTCs, Dr. Haber’s team identified mechanisms in these cells that help them remain stable enough to replicate without negative consequences. This stability mechanism presents an intriguing therapeutic target which they will study this year.
Dr. Haber is Director of the Massachusetts General Hospital Cancer Center and the Kurt J. Isselbacher Professor of Oncology at Harvard Medical School. His laboratory interests have focused on the area of cancer genetics, including the etiology of the pediatric kidney cancer Wilms tumor, genetic predisposition to breast cancer, and targeted cancer therapies. His laboratory reported that lung cancers with activating mutations in the epidermal growth factor receptor (EGFR) are uniquely sensitive to tyrosine kinase inhibitors that target this receptor. This observation has had important implications for the genotype-directed treatment of non-small cell lung cancer, and more broadly for strategies to identify critical genetic lesions in cancers that may serve as an "Achilles heel" and be suitable for molecular targeting. In collaboration with Dr. Mehmet Toner’s laboratory, Dr. Haber’s laboratory has recently established the application of a novel microfluidic technology for quantifying and purifying Circulating Tumor Cells (CTCs) from the blood of patients with various epithelial cancers. This new application has potentially profound implications for early diagnosis of cancer and for noninvasive molecular profiling of cancers during the course of therapy. Building on his early studies in breast cancer that characterized contributions of founder mutations in BRCA1 and CHEK2 to early onset breast cancer, Dr. Haber’s most recent work has applied digital RNA profiles of breast CTCs for pharmacodynamic monitoring of estrogen receptor signaling following therapy, and the generation of ex vivo breast CTC cultures to define functional properties of these metastatic precursor cells.
Dr. Haber received his MD and PhD degrees at Stanford in 1983, completed an internal medicine residency at MGH, clinical oncology training at the Dana-Farber Cancer Institute, and a postdoctoral research fellowship at MIT. He joined the faculty of Harvard Medical School in 1991. Dr. Haber’s numerous awards include a MERIT Award from the National Cancer Institute, the Doris Duke Distinguished Clinical Scientist Award, and a Dream Team Award from Stand Up To Cancer. He received the Richard and Hinda Rosenthal Memorial Award from the American Association for Cancer Research (AACR). He was appointed to the Howard Hughes Medical Institute in 2008 and elected to the Institute of Medicine/National Academy of Medicine in 2009, the American Academy of Arts and Sciences in 2011, the National Academy of Sciences in 2018, and as a Fellow of the AACR Academy in 2019.
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