Gene Regulation in Stem Cells, Cell Plasticity, Differentiation, and Cancer

Problem

Organisms are made up of hundreds of different types of cells, each with specific attributes and functions. This diversity of cellular identities and roles is determined by a particular 'gene expression signature' that. This signature defines each cell type, but it is not fixed and evolves as cells change in physiological conditions and diseases.

Gene expression is regulated at multiple levels, including by some proteins (known as “transcription factors”) that bind to regulatory regions of DNA to turn gene expression on or off. Understanding how genes are regulated is critical to designing tools to maintain health as well as to prevent and cure disease.

Approach

Cells and tissues change their identity (phenotype) and function to adapt to environmental changes. This process, known as “cellular plasticity,” occurs under physiological conditions in response to stress and injury (e.g., inflammation, tissue regeneration by normal stem cells), but also allows cells to adopt a pathological identity and/or function (e.g., tumor initiation by cancer stem cells).

The group studies the gene regulation of cell plasticity during normal cell differentiation (the temporal process by which cells, tissues and organs change to carry out specific functions) and in disease. Ongoing projects in the group study gene regulation of cell plasticity in stem cells, inflammation, cancer, cell differentiation and tissue regeneration. Cellular plasticity is orchestrated by transcription factors and/or epigenetic modifications, and we focus on the cellular plasticity factors ZEB1 and ZEB2 that play a key role in all these physiological and pathological processes.

Our research uses multiple technical approaches ranging from unique conditional transgenic mice, ex vivo culture and stem cell manipulation to high-throughput techniques (OMICs: RNAseq, single cell-RNAseq, metabolomics, etc.) and human embryonic stem cell differentiation.

Impact

Through the study of how gene expression is regulated under physiological conditions and how it is altered in disease, and investigating the mechanisms that regulate gene expression, our group aims to: a) identify markers that allow us to follow the onset and progression of diseases and b) inform the design of new and more personalized therapies that allow restoring normal gene expression and function.