Project Summary Basic and translational research in hematology has been at the cutting edge of recent advances in our understanding of the molecular pathophysiology of disease for decades. This T32 grant, for which we request renewal, was submitted 5 years ago to replace the former Harvard Medical School Training Program in Molecular Hematology, which had a distinguished 25-year track record in training graduate students and postdoctoral fellows in the study of blood and its disorders, with many graduates of the program going on to highly successful academic careers. The past 30 years have seen many changes in the landscape of hematology-oncology in the Harvard Medical area, with the merging of the Hematology program at the Brigham and Women?s Hospital with the oncology programs at the Massachusetts General Hospital and the Dana-Farber to form a combined Hematology-Oncology fellowship. This has had many positive effects on the opportunities for clinical and research training, complemented by a proliferation of training programs. At the same time, an explosion of new technologies has ushered in an era in biomedical research that offers exciting opportunities for major breakthroughs in our understanding of human disease, offering hope for new clinical paradigms that can transform the treatment of many hematologic disorders. However, the loss of a dedicated Hematology fellowship has made us acutely aware of the importance of nurturing physician scientists dedicated to the study of hematology. Indeed, the disappearance of free-standing hematology fellowships nationwide and the shrinking numbers of Hematology trainees signals an urgent need to encourage future academic hematologists. This program places high priority on training physician-scientists focused on hematology, and we have been gratified to see an increasing number of clinical fellows who choose to do research as trainees on this grant. To date, we have accommodated all the MD and MD/PhD fellows with a research focus on Hematology, although we have a selection process in place should we have to limit availability because of an increase in interested fellows. This process has already been used in the first two years of the grant to select PhD fellows to fill available slots, although all subsequent slots have been taken by physician scientists. The primary site of training is the preceptor?s laboratory, but each trainee is expected to participate in relevant seminars and courses within the HMS community. Each trainee also assembles a training committee that monitors research progress with annual formal presentations. We strongly encourage the investigation of benign hematologic disorders in the areas of red cell disorders, iron metabolism, hemostasis and thrombosis, and neutrophil disorders, as well as hematologic malignancies such as leukemia, myelodysplasia, and myeloproliferative neoplasms. This strict focus on Hematology distinguishes this grant from other Harvard-related training grants, fulfilling a need that is not answered by any other training grant within adult medicine. We request renewal of this application with its 8 current training positions.!