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Jean Zhao, PhD

Professor, Biological Chemistry & Molecular Pharmacology
Harvard Medical School
Professor, Cancer Biology, Dana-Farber Cancer Institute
Co-leader, Breast Cancer Program, Dana-Farber/Harvard Cancer Center
Boston, Massachusetts

Current Research

Goal: To identify new strategies for the treatment of metastatic breast cancer (MBC), particularly breast cancers that have spread to the brain.

Impact: Dr. Zhao has been studying how breast tumors evade attack by the immune system and evaluating treatments against breast cancer brain metastases. Her work has the potential to significantly reduce the burden of advanced breast cancer, particularly brain metastases, and to improve the lives of patients affected by this disease.

What’s next: She and her team will continue to develop effective therapeutic strategies against specific subtypes of breast cancer and brain metastases using sophisticated laboratory models of breast cancer metastasis.

MBC is breast cancer that has spread beyond the breast and nearby lymph nodes to other organs in the body. The brain is a common site of breast cancer metastasis. Breast cancers that have spread to the brain present a unique clinical challenge for doctors, making new treatments a clinical priority. Dr. Zhao is conducting studies on the effectiveness of combinations of targeted and immunotherapies directed against specific molecular abnormalities typically found in advanced and metastatic breast cancer.

Full Research Summary

Research area: Developing safe and effective combinations of targeted and immunotherapies for metastatic breast cancer (MBC).

Impact: Patients who have advanced breast cancer—particularly those with brain metastases—frequently face a poor prognosis and limited treatment options. Significant clinical challenges remain including drug resistance, treatment toxicity, and lack of effective therapies against recurrent disease. Dr. Zhao is conducting laboratory tests of highly promising drugs and immunotherapy combinations that target vulnerabilities of MBC cells. The results of her studies will provide important pre-clinical information to guide the rational design of promising clinical trials. Her work may have profound implications in advancing treatment options for patients with MBC.

Current investigation: Dr. Zhao and her colleagues are investigating how breast tumors affect the gut microbiome, and how this impacts the anti-tumor immune response of targeted- and immuno-therapies. In addition, they will investigate how the establishment of an immune suppressive tumor microenvironment promotes resistance to PARP-inhibitors and evaluate strategies to overcome this resistance. 

What she’s accomplished so far: Dr. Zhao and her team have developed and characterized several laboratory models of invasive triple-negative breast cancer (TNBC). In preliminary experiments, they showed that a build-up of an immune suppressive tumor microenvironment could negate the anti-tumor efficacy of PARP inhibition. 

What’s next: The team will build upon their findings utilizing the laboratory models they have developed. This includes analyzing how breast tumors affect the gut microbiome and impact the anti-tumor response of targeted- and immuno-therapies. They will also assess the role of the tumor immune environment in promoting resistance to PARP-inhibitor treatment.

Biography

Jean Zhao is Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and Dana-Farber Cancer Institute (DFCI). Dr. Zhao’s research centers on understanding kinase signaling pathways in cancer. She has pioneered a new front in understanding signal transduction by integrating genetics and pharmacological approaches, thus changing the way we think about important problems in the targeted therapy of cancer. Specifically, she has conducted seminal work to determine distinct roles of isoforms of PI3K in the normal physiological functions and in the pathogenesis of cancer. Her work laid a foundation for the new field of targeting isoforms of PI3K in cancer and guided the design of current clinical trials of PI3K inhibitors for cancer patients. Dr. Zhao is a leader in the systems and functional approaches to targeting kinases in cancer, and has identified a number of novel oncogenic kinases and lead compounds, providing the groundwork for innovative therapeutic interventions. More recently, she is leading a major effort to establish patient-derived models of metastatic breast cancer. This work is designed to investigate the molecular and genetic basis for this disease and the mechanisms of drug resistance in order to translate fundamental preclinical findings into novel and improved therapeutic strategies for patients. Dr. Zhao’s honors and awards include Career Development Awards from NIH/NCI, V Scholar Award and Starr Foundation Award. She is a member of Committee for Women Faculty and Executive Committee for Research at DFCI, and serves as Co-Leader of the Breast Cancer Program at Dana-Farber/Harvard Cancer Center.

Grid Researcher Headshot - Zhao

BCRF Investigator Since

2015

Donor Recognition

The Ann Taylor and LOFT Award