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The human body sheds and replaces hundreds of billions of cells every day. This remarkable regenerative capacity is fueled by populations of stem cells that reside in our blood, intestine, skin, muscle and other organs. A fundamental question in regenerative biology concerns how these stem cells perform behaviors such as self-renewal and differentiation at the right times and places to support lifelong maintenance of our tissues. In the Cockburn lab, we want to understand this problem in the context of skin, the essential barrier that protects us from the environment and one of the most high-turnover tissues in our bodies. Using intravital imaging, we watch stem cells in the living skin and follow their behaviors over hours, days or even weeks as regeneration is taking place in real time. By combining this approach with signaling reporters, genetic perturbations and transcriptomics, we aim to build a picture of how healthy regeneration is orchestrated at the level of individual cells, local cellular neighborhoods and tissue-wide cues. We also want to understand how and why stem cell behaviors go awry in in situations of cutaneous disease and malignancy. Our questions of interest include:

1. How does crosstalk between stem cells shape regeneration?
Our previous and ongoing work has shown that epidermal stem cells act as a dynamic and constantly evolving niche for one another, sending and receiving cues that pattern regenerative behaviors across space and time. We want to elucidate the secreted signals and mechanical cues that underlie this crosstalk in the healthy epidermis and understand how local communication changes in the presence of oncogenic mutations.
2. How do stem cells adapt to changing environmental demands?
The skin faces the unique challenge of protecting our bodies from a constantly changing environment that includes irritants, mechanical stressors and pathogens. We want to understand how epidermal stem cells sense and respond to these challenges, with a particular focus on the role of their differentiating daughter cells, which serve as the physical intermediaries between stem cells and the outside world.
3. How do stem cell behaviors contribute to the progression of cutaneous disease?
Mutations in structural and signaling components can lead to a range of congenital skin conditions characterized by blistering, scaling and inflammation. In many cases these diseases occur mosaically, meaning that patches of mutant and healthy cells are interspersed in a patient’s skin. We are generating novel mouse models that will allow us to visualize and track both types of cells in living tissue. Our goal is to enhance the survival and expansion of healthy cells to improve disease prognosis and generate new sources for grafting treatments.