The adaptive role of phenotypic plasticity in cancer
Cancer can acquire traits like rapid growth, immune evasion, and drug resistance through both genetic mutations and non‑genetic changes in gene expression. We study how tumor cell lineages adapt to new environments using joint single‑cell DNA and RNA sequencing, focusing on papillary thyroid and colorectal cancers. Our goal is to reveal how phenotypic plasticity and heritable changes drive cancer progression and to uncover insights for better diagnosis and therapy.
Single-cell cancer phylogeography
The discovery of extensive intratumor heterogeneity, together with the rise of single-cell genomics, has created a unique opportunity to study the phylogeography of cancer tumor cells. We are sequencing and analyzing single-cell genomes in colorectal cancer to understand the tempo and mode of evolution of cell lineages within and between cancer tumors. By doing so, we aim to construct a robust theoretical and methodological evolutionary framework that will contribute to a better understanding of somatic evolution and shed light on the biology of cancer.
Evolutionary genomics of circulating tumor cells
Circulating tumor cells (CTCs), typically found in cancer patients at a frequency of one per billion normal blood cells, are thought to be the source of distant metastases, a process responsible for 90% of the deaths associated with cancer. We are using cancer animal models, single-cell sequencing, and evolutionary biology to identify the genomic characteristics of CTCs and CTC clusters that form metastases and to understand when, where, and how CTCs and CTC clusters originate and propagate. A better understanding of the genomics and biogeographic history of CTCs and CTC clusters should prove instrumental in uncovering new vulnerabilities for cancer treatment.