Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become widely applied for hematological (and more recently even for non-hematological) disorders. However, allo-HSCT is a “two-edeged” swords; this treatment has preferable strong graft-versus-tumor effects (GVT) to cure diseases while at the same time this causes graft-versus-host disease (GVHD) that could lead to the adverse prognoses of treated patients. As a hematologist I observed many of the complications including GVHD after allo-HSCT, and also as a researcher I elucidated the effects of GVHD on hematopoiesis/hematopoietic niche, I keep on pursuing my research in this field of transplantation immunology trying to reveal the detailed mechanisms of GVHD and GVT. After joining in the lab since April 2011, I have been focusing attention on a network hub controlling immunity, inflammation, and cancer - especially a transcriptional factor c-Rel that controls T-cell activation and proliferation contributing to pathophysiology of GVHD/GVT. We have small molecule c-Rel inhibitor compounds in our hands and by utilizing these compounds in vivo and in vitro, we observed effective suppression of c-Rel resulting in improved GVHD while preserving GVT activity. Intestinal damages are also important to initiate/sustain GVHD, so my projects also include models using knock-out mice of specific genes relevant to intestinal immune homeostasis. In addition, I am also involved in the project focusing on mucosal immunology and examine how it can impact on intestinal GVHD, including the microbial flora and dietary factors. The ultimate goal is to develop promising methods to improve clinical outcomes of allo-HSCT.
Honors and Awards
- Fellowship Award from the Uehara Memorial Foundation (2011-2013)
- ASH Abstract Achievement Award (2012)
- ASH Abstract Achievement Award (2013)
- ASBMT Best Abstract Award (2013)
- ASBMT Best Abstract Award (2014)
- ASH Abstract Achievement Award (2014)
- ASBMT Best Abstract Award (2015)
Ongoing Research Support
Lymphoma Research Foundation, Post-Doctoral Fellowship (2013-2015)
ASBMT New Investigator Award (2015-2017)
Patients receiving an allogeneic hematopoietic stem cell transplant often develop neutropenic fever, which is treated with antibiotics. Such antibiotic treatment also may inadvertently wipe out beneficial intestinal bacteria that reduce gut inflammation. Transplant patients treated with certain broad-spectrum antibiotics show an increase in graft-versus-host disease in the colon (Shono et al.). Analysis of a mouse model revealed that this was due to loss of beneficial gut bacteria and overgrowth of bacterial strains that consumed the protective mucus layer of the colon rendering it more susceptible to inflammation and injury.