My laboratory focuses on understanding the molecular basis of T lymphocyte differentiation and function. In particular, we have employed forward and reverse genetic approaches to elucidate the signaling and transcriptional pathways that regulate these processes. In the course of this work, we have generated numerous new transgenic and knockout mouse models, most recently to assess the specific and redundant roles of ThPOK as a key regulator of T cell development, and to dissect its expression pattern and transcriptional control mechanisms in vivo. We have also initiated work in the zebrafish model, in order to exploit the advantages of this system for genetic screens to identify novel regulators of T cell development and lymphomagenesis. Thus, we have generated new CD4 and ThPOK reporter fish, as well as ThPOK knockout fish, which will both greatly facilitate the study of T helper development and function in zebrafish, and provide the basis for their efficient genetic dissection. Finally, we have discovered a new and so far unrecognized role of ThPOK as an oncogene, using novel animal models that we have generated. This work suggests a widespread and important role of ThPOK in diverse human cancers, and has become a major new focus of my lab. Our work in elucidating the process of CD4/CD8 lineage choice and identifying the key role of ThPOK represents a unique and widely recognized contribution to the field. These findings have important implications for therapeutic manipulation of the cell-based immune system including potentially for cancer treatment.