Primary Appointment

Dual/Joint/Adjunct Appointment

My goal is to understand genome evolution in human cancers. As tumors evolve from a single cell, they acquire complex somatic mutations and diverge to form distinct lineages and subpopulations. This intratumor heterogeneity confounds basic research and clinical diagnosis, because tools do not exist to resolve it. To address this problem, we developed a single-cell sequencing method to profile genomic copy number in individual tumor cells (Nature 472:90-4, 2011). I used this method to profile hundreds of single cells in two breast cancer patients to delineate clonal diversity and infer patterns of genome evolution. The data revealed multiple clonal subpopulations that shared a common evolutionary lineage. In contrast to the gradual models of tumor progression, the data suggest that these breast tumors grew by punctuated clonal expansions, in which hundreds of genomic rearrangements were acquired in short bursts of evolution. We have also recently developed a powerful new method to perform whole-genome sequencing on single tumor cells. This will enable us to study the evolution of many different classes of somatic mutations (point mutations, indels and structural variants) at base-pair resolution in single cells. In addition to single cell sequencing, my laboratory also uses many genomic and cytological methods to study how cancer genomes evolve. We are also actively developing new computational methods to quantify tumor heterogeneity and understand if these measures correlate with clinical parameters such as survival and resistance to chemotherapy. One method developed is called Ploidy-Seq to deep-sequence intratumor subpopulations and infer mutational chronology and ancestral tumor genomes.

View a complete list of Dr. Navin's publications.

Last updated: 3/4/2013