Research Interests
My lab is primarily focused on studying the “life history” of the thymus, the primary lymphoid organ responsible for the generation of T cells. This approach encompasses the evolution, fetal development, postnatal function, and aging of this critical organ. Our basic hypothesis is that these diverse aspects of the biology of the organ are controlled by common regulatory networks, cellular dynamics, and physiological processes. We also study the parathyroid, which is required for calcium homeostasis, and has a shared developmental ontogeny with the thymus. We use a variety of approaches to accomplish these goals, including genetic analysis of tissue-specific and inducible mutant mouse strains, comparative and experimental embryology, and immunological techniques.
Evolution of the pharyngeal organs: The thymus and parathyroids are only present in jawed vertebrates. We are using our knowledge of early organogenesis to investigate the evolutionary origins of these organs. This approach may allow us to identify mechanisms by which vertebrates have evolved "newer" functions, such as adaptive immunity, from evolutionarily ancient embryonic structures.
Organogenesis and morphogenesis: Projects include the molecular and cellular control of thymus and parathyroid organogenesis, and crosstalk between thymic epithelial cells and the multiple cell types in the fetal and postnatal thymus.
Thymic epithelial cell development and function: Projects are focused primarily on the role of the Foxn1 transcription factor in thymic epithelial cell differentiation and function, during both fetal development and in the postnatal thymus.
Thymic involution and immunosenescence: The thymus is the earliest organ to degenerate, losing much of its structural and functional integrity by early adulthood. This process of involution is a major contributor to immunosenescence. Our work to date suggests that the molecular mechanisms regulating fetal development may provide insight into the mechanisms regulating thymic involution.