How does an organism grow? How do cells, tissues and organs in the body know where, when and what to grow? How do they know when to stop? Resident in many adult tissues are stem cells that are the driving force behind the body’s ability to grow, repair injuries and maintain homeostasis. In order for stem cells to orchestrate these processes, their function must be coordinated in time, space and scale.
Our research is focused on understanding the pathways that link an organism’s physiological requirements with stem cells’ response to fulfill those needs. We combine mouse models of tissue growth, repair/regeneration and homeostasis with stem cell-specific genetic tools and single cell analyses to dissect the signals that regulate stem cells, the cellular/behavioral response to those signals and the molecular pathways involved. The goal of our research is to translate the biologic mechanisms that regulate stem cells into therapies to control stem cells. The direct applications of this research are in improving regenerative medicine, tissue transplantation and tissue engineering.
Work in the laboratory is largely rooted in the study of stem cell quiescence — a state in which a stem cell is not committed to cell division, but maintains the capacity to divide. The role of quiescence is to preserve stem cells until they are called upon to participate in tissue growth or repair. Our group has found that there are at least two distinct sub-phases within the stem cell quiescent state and that stem cells dynamically transition between these phases in response to physiological cues. Stem cells can enter an “alert” phase of quiescence in which they are extremely responsive to environmental stimuli or a phase of deep quiescence in which they are resistant. This regulation of quiescence changes how stem cells interpret their environments. We are investigating how the body uses this and other mechanisms to regulate and coordinate stem cell function, in tissue growth and repair across large anatomical distances.
The process of aging is intimately linked with growth. There are many stereotypic changes that develop in an organism through the course of aging: the skin thins, wrinkles and doesn’t heal efficiently; muscle loses mass, strength and flexibility; etc. Like in growth, many of the changes observed in aging are dependent upon the coordinated behavior of stem cells that build and maintain tissue. But in aging, the coordination between stem cells is impaired, and the tissue produced is dysfunctional. We are studying how stem cells change in aging and how changes in stem cell function contribute to the pathology of aging.
Projects in the lab revolve around using stem cell behavior as a tool to discover the biological signals that regulate that behavior and the molecular pathways involved. The laboratory primarily uses skeletal muscle stem cells as a model system, due to the extremely powerful and specific genetic tools available in this system and some unique biological attributes of these cells. We also work with mesenchymal, epidermal, hair follicle and hematopoietic stem cell systems. We utilize a broad spectrum of tools to interrogate how stem cells respond to environmental cues to regulate tissue function: stem cell-specific genetic mouse models, parabiosis, single cell analyses, live cell imaging and physiological interventions. We perform our studies in mouse models of human (patho) physiological tissue growth, injury-repair, aging and disease to understand these conditions and develop therapies to restore healthy function.