Michele Anderson

Biography

Our overarching goal is to understand how T cells develop from stem cells, at the molecular and cellular levels. During embryonic development, three germ layers are formed: endoderm, ectoderm and mesoderm. Mesodermal tissues give rise to hematopoietic stem cells, which can become any of the eight major blood cell types, including T cells. As these processes occur, new genes are expressed while others are shut down, as directed by proteins known as transcription factors. We are studying two related transcription factors, HEBAlt and HEBCan. HEBCan is broadly expressed, whereas HEBAlt appears to be highly regulated to early stages of T cell development. We have evidence that both HEBAlt and HEBCan are involved in directing hematopoietic stem cells to become T cells and that they can regulate the ability to produce cytokines, which convey important signals to immune cells during immune reactions. We use embryonic stem cell differentiation and mouse models to study the HEB factors by disrupting or changing their functions using genome editing. Using human embryonic stem cells, we have found that HEB factors are important in the generation of mesoderm, the formation of hematopoietic stem cells and T cell development. In the mouse, we have found that HEBAlt promotes the development of T cells from hematopoietic stem cells in concert with other transcription factors such as Notch and Bcl11b. Moreover, HEB factors are essential for the genetic programming of a specific type of T cell called gamma delta T cells, which reside in mucosal tissues such as the lung, reproductive tract and intestines. Without HEB, these cells are unable to make IL-17. IL-17, while important for barrier immunity, is linked to many autoimmune diseases. Finding ways to control HEB activity may thus enable modulation of these conditions, including multiple sclerosis and psoriasis. Our long-term goal is to understand how HEB factors work within the context of the gene regulatory networks that drive cell identity and function. Ultimately, it is in these interaction networks that new ways of controlling the generation of specific blood cell types will be found. In addition, our work is providing valuable insights into how to maximize immunity against infection while providing protection against autoimmunity. Our studies of human embryonic development have also provided a compelling rationale for further studies into genetic defects and disorders that could result from misregulation of HEB factors.

Research Interest

Transcriptional regulation of T cell development