We employ a multidisciplinary approach that integrates computational and experimental strategies. Through collaborations with clinicians and researchers, we have access to patient samples and preclinical models, focusing on pancreatic and colorectal cancer. By integrating single-cell multi-omics data, imaging and computational methods, our lab aims to dissect the cancer cell intrinsic traits and microenvironmental signals that promote metastasis and therapy resistance.
The main areas of focus are:
Cancer cell plasticity
Cancer cells maintain an intrinsic plasticity that allows them to reversibly change their phenotype in response to microenvironmental signals and switch between cellular states. Single-cell studies have revealed extensive transcriptional heterogeneity along with lineage mixing and plasticity in several cancer types. In metastases, cells co-opt developmental programs and are reset to an even more primitive differentiation state, mimicking organ formation to reinitiate growth in a new location.
Using patient samples and multi-omics single-cell and bulk data, we are investigating the genetic vs non-genetic tumour heterogeneity and the regulatory networks underlying plasticity and emergence of pro-metastatic traits during metastasis.
There is a growing understanding that the metastatic microenvironment is crucial in enabling the growth of disseminated cancer cells. In addition to the tumour cell intrinsic plasticity, local niche factors from stromal and immune cells influence tumour cell phenotypes and likewise, distinct cancer phenotypes shape the tumour microenvironment. Our aim is to understand how cancer cells adapt to the metastatic niche and how in turn, immune and stromal cells support tumour cell plasticity and metastasis formation.
We focus on dissecting the role of myeloid and stromal cells in promoting or restricting tumour cell plasticity, emergence of pro-metastatic traits and metastatic seeding. Using patient samples and mouse models through collaborations with other researchers, in combination with single-cell omics and spatial data, we aim to dissect the complex molecular crosstalk within pre-metastatic and metastatic niches.
Accumulating evidence implicates phenotypic plasticity as a key mechanism towards development of resistance to both targeted and immunotherapy. We aim to understand the molecular and cellular mechanisms driving phenotypic transitions in therapy resistance. By characterising the repertoire of phenotypes present both prior to and after therapy exposure, we are investigating the phenotypic states that promote resistance and their therapeutic vulnerabilities.
Our overarching goal is to identify key targets that drive metastasis formation and therapy resistance and find potential therapeutic strategies that disrupt crucial tumour-microenvironment interactions.