Christina Curtis, PhD

2012-2013 BCRF Project:
(made possible by generous support from The Housewares Charity Foundation)
Co-Investigator: Sir Bruce A. J. Ponder, PhD, FRCP, FRS, University of Cambridge, Cancer Research UK, Cambridge, United Kingdom

Drs. Ponder and Curtis have made substantial progress in developing approaches to study the heterogeneity of individual breast cancers. Their current efforts are focused on characterizing the extent of this intra-tumoral diversity and identifying the molecular drivers that characterize both large and small families (clonal populations) of cancer cells as these may represent actionable mutations. With the technological and computational tools in place, Drs. Ponder and Curtis aim to extend their novel approach to larger numbers of representative samples from the patient population so that their findings may be generalized to improve patient care and in the development of individualized therapies.

This approach represents a paradigm shift in the molecular profiling of breast cancer that will address unanswered questions concerning the variability in tumor phenotypes and treatment response. This research will also shed light on underlying mechanisms of tumorigenesis and may help to clarify the contributions of cancer stem cells and clonal evolution to tumor heterogeneity. With the experimental and computational tools in hand, this team will continue their efforts to reconstruct the subclonal ancestry of cell populations within an individual tumor and their associated mutational events. In particular, they will focus on identifying the molecular drivers that characterize both rare and dominant clonal populations, as they may represent actionable mutations.

Drs. Ponder and Curtis have now applied their novel experimental and analytical framework in order to interrogate the mutational diversity and subclonal architecture of a subset of breast cancers. Their approach is unique in that it enables the quantification of intra-tumor heterogeneity and tumor dynamics, with implications for personalized treatment. This team will observe extensive intra-tumoral heterogeneity on multiple spatial scales, as well as variability in tumor organization between patients, and are now analyzing additional samples in order to determine the clinical relevance of their findings.

Mid-year Progress: Drs. Curtis and Ponder will continue to investigate the evolutionary dynamics underlying tumor progression and therapeutic resistance. In particular, using high-throughput genomic data derived from breast cancer samples, they will measure patient-specific parameters such as the fraction of cancer stem cells, mutation rate, and the extent of genetic heterogeneity, and will determine whether these features are associated with clinical outcome. Using these and other data, they will exploit their computational framework in order to predict optimal treatment strategies.

Bio:
Christina Curtis, PhD is an Assistant Professor of Preventive Medicine at the Keck School of Medicine of the University of Southern California and a member of the Norris Comprehensive Cancer Center. She obtained her bachelor of science degree from the University of California, Los Angeles in 2001 and went on to obtain a master's degree in Molecular Biology from the University of Heidelberg, Germany, a master's degree in Bioinformatics from the University of Southern California, and a doctorate in Molecular and Computational Biology in 2007. She subsequently completed a postdoctoral fellowship in Computational Biology at the University of Cambridge before assuming her current position in 2010.

Dr. Curtis's laboratory pursues innovative experimental approaches and data-driven modeling to address outstanding questions in cancer systems biology. In particular, her research seeks to delineate mechanisms of tumor progression and therapeutic resistance. She and her team have developed a framework to interrogate tumor dynamics at high-resolution, enabling a shift in patient molecular profiling with implications for personalized treatment strategies. Another aspect of her research has focused on the integration of diverse genomic data types to elucidate inter-individual variation and mechanisms of tumorigenesis. For example, she lead a seminal study that redefined the molecular map of breast cancer through a detailed characterization of the genomic and transcriptomic landscape of 2,000 breast cancers. Using integrative genomics and statistical approaches this work uncovered novel subtypes of breast cancer with distinct clinical outcomes and subtype-specific driver genes, which will guide the development of targeted therapeutics.

Dr. Curtis was the recipient of the 2009 American Association of Cancer Research Scholar in Training Award and the 2012 STOP CANCER Research Career Development Award.