Organisms are comprised of hundreds of different types of cells, each with a specific attribute and function. This diversity of cell identities and roles is determined by a particular 'gene expression signature'. This gene signature defines each cell type but it is not fixed and evolves as cells change in physiological conditions and in disease.
Gene expression is regulated at multiple levels, including by some proteins (known as “transcription factors”) that bind to the regulatory regions in the DNA to switch on/off gene expression. Understanding how genes are regulated is critical for designing tools to maintain health and to prevent and cure diseases.
Cells and tissues change their identity (phenotype) and function to adapt to environmental changes. This process, known as “cellular plasticity”, occurs under physiological conditions as a response to stress and injury (e.g., inflammation, tissue regeneration by normal stem cells) but also allows cells to adopt a pathological identity and function (e.g., tumor initiation by cancerous stem cells).
The group studies gene regulation of cell plasticity during normal cell differentiation (the process through 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, and cell differentiation and tissue regeneration. Cellular plasticity is orchestrated by transcription factors and epigenetic modifications and we focuses on the ZEB1 and ZEB2 cell plasticity factors that play key roles in all of these physiological and pathological processes.
Our research uses multiple technical approaches ranging from unique conditional transgenic mice, ex vivo cultures and manipulation of stem cells to high-throughput techniques (OMICs: RNAseq, single cell-RNAseq, etc) and differentiation of human embryonic stem cells.
By understanding the mechanisms that regulate gene expression and how gene expression is regulated under physiological conditions and altered in disease, our group aims to: a) define markers that trace the initiation and progression of diseases and b) inform the design of new and personalized therapies that restore normal gene expression and function.