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Xiaole (Shirley) Liu, PhD
Professor, Statistics, Biostatistics and Computational Biology,
Harvard Medical School
Director, Center of Functional Cancer Epigenetics
Dana-Farber Cancer Institute
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 received PhD in Biomedical Informatics and PhD minor in Computer Science from Stanford University in 2002. She is now Professor of Statistics, Biostatistics and Computational Biology at Harvard University, Director of the Center of Functional Cancer Epigenetics at Dana-Farber Cancer Institute, and Visiting Professor of Bioinformatics at Tongji Univ.
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.
Her lab developed widely used analysis algorithm for transcription factor motif discovery, ChIP-chip/seq, CRISPR screen, and immune repertoire data analysis. Her computational modeling helped the understanding of ER, AR, FoxA1, XBP1, EGIN2, JARID1B regulation as well as BET bromodomain inhibitor, gamma secretase inhibitor, and CDK4/6 inhibitor function in breast cancers.
Dr. Liu has an H-index of 73 according to Google Scholar statistics and has published over 50 papers in Nature, Science or Cell series journals. She is the recipient of the Sloan Research Fellowship, the Richard E. Weitzman Outstanding Early Career Investigator Award from the Endocrine Society, the Claire W. and Richard P. Morse Research Award, Yangtze River Scholar and 1000 Talent Scholar in China, and the Breast Cancer Research Foundation Investigator. Since becoming a faculty in 2003, she has successfully mentored fourteen trainees to start tenure track faculty positions.
BCRF Investigator Since
The Estée Lauder Companies’ North America Manufacturing & Distribution and Global Research & Development Award