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Xiaole (Shirley) Liu, PhD
Professor of Biostatistics and Computational Biology
Department of Data Sciences
Dana-Farber Cancer Institute
Harvard T.H. Chan School of Public Health
Goal: To identify patients who are most likely to respond to immunotherapy.
Impact: Dr. Liu has used new technologies to identify therapies that can enhance the efficacy of current treatments for estrogen receptor (ER)-positive and triple negative breast cancers (TNBCs), predict patient response to immunotherapies, and study information from tumors that could be useful for early cancer diagnosis and therapies.
What’s next: She and her team will study the function of a gene that may work synergistically with immunotherapy in TNBC. They also plan to develop a method of analyzing individual cells for molecular markers that could predict how tumors respond to different drugs.
Of the various subtypes of breast cancer, TNBC is the one most likely to respond to current immunotherapies, but the response rate remains very low. Dr. Liu is seeking to identify biomarkers that could identify patients most likely to respond to these therapies and is also investigating combination approaches that may improve response to immunotherapy in patients with TNBC.
Full Research Summary
Research area: Improving response to immunotherapy by discovering new biomarkers and therapeutic targets.
Impact: Immunotherapy is an exciting new treatment in several cancers, including some triple negative breast cancers (TNBC); however, most TNBC patients do not respond to it. Dr. Liu is pursuing biomarkers that could help predict response, which may lead to the development of lab tests that can help guide treatment decisions.
Current investigation: She and her team have been validating a computation model they developed called TIDE (Tumor Immune Dysfunction and Exclusion), which measures the immunogenicity of tumors—meaning how well they will respond to immunotherapy. TIDE has been able to predict response to immunotherapy in laboratory studies.
What she’s learned so far: Dr. Liu identified a gene that regulates protein degradation. When inhibited, this gene synergizes with immunotherapy in triple negative breast cancer.
What’s next: The team will continue to study this gene and begin a systematic computational investigation of mutations that influences protein degradation in cancers. They also plan to develop computational algorithms to analyze two single-cell technologies, in which individual breast cancer cells, rather than a collection, are screened for molecular markers. This technique would help better model gene regulation and tumor response to different drugs.
X Shirley Liu is Professor of Biostatistics and Computational Biology at Harvard University and the Director of the Center of Functional Cancer Epigenetics at Dana-Farber Cancer Institute. Her research focuses on algorithm development and integrative modeling of high throughput genomic data to understand the specificity and function of regulator genes in tumor development, progression, drug response and resistance. She is especially interested in genomics and bioinformatics approaches in cancer epigenetics, cancer immunology, and CRISPR screens for translational cancer research. She is interested in how nuclear receptors, epigenetic regulators, and protein degradation regulators influence breast tumor growth and breast tumor immunity. She is the PI of the Cancer Immune Data Common, a cancer moonshot project from National Cancer Institute with the goal of identifying biomarkers for optimizing cancer immunotherapy strategies. She has an H-index of 91 and has published over 60 papers in Nature, Science, or Cell series journals. Since becoming a faculty in 2003, she has successfully mentored eighteen trainees to start tenure track faculty positions. She is the recipient of the Sloan Research Fellowship, the Richard E. Weitzman Outstanding Early Career Investigator Award from the Endocrine Society, Breast Cancer Research Foundation Investigator and a fellow of the International Society of Computational Biology.
BCRF Investigator Since
The Estée Lauder Companies’ North America Manufacturing & Distribution and Global Research & Development Award