My research focuses on understanding basic mechanisms of allogeneic immune response with the overarching goal of improving the clinical application of allogeneic hematopoietic cell transplantation (HCT). My laboratory utilizes modern cellular and molecular immunologic techniques and diverse experimental approaches pertaining to immunomodulatory drug development, mouse models of graft-versus-host disease (GVHD), and the study of primary patient specimens from early phase clinical trials. Currently, there are three principal lines of investigation. First, we are studying the mechanisms critical for induction and maintenance of tolerance and modulation of GVHD and graft-versus leukemia (GVL) responses in allogeneic chimeras. Second, we are performing studies to decipher the mechanisms behind cyclophosphamide (Cy)-induced immunologic tolerance as a method to suppress GVHD without causing global immune incompetence. Finally, ongoing laboratory and translational studies are focused on deciphering the interplay between the immune system and leukemia in an effort to overcome immune evasion mechanisms and augment anti-leukemia immunity after chemotherapy and post-HCT. An exciting outcome of this work has been the clinical development of post-transplantation Cy (PTCy) as GVHD prophylaxis in the human leukocyte antigen (HLA)-matched and HLA-mismatched (haploidentical) settings and the discovery that regulatory T cell resistance to Cy through expression of aldehyde dehydrogenase may contribute to the clinical activity of PTCy. The efficacy of PTCy in GVHD prevention has resulted in the growing utilization of HLA-haploidentical donors for allografting patients with hematological malignancies and the applicability of this strategy to the treatment of non-malignant hematologic diseases.