School of Medicine
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Yusuke Nakauchi M.D., Ph.D.
Postdoctoral Research fellow, Stanford Cancer Center
Current Research and Scholarly Interests From 2005 to 2010, my work as a clinical hematology fellow allowed me to experience first-hand how scientific advances that started in a laboratory can transform the lives of patients. While many of my patients were cured of their disease with allogeneic hematopoietic stem cell transplantation, underscoring the importance of anti-tumor immunotherapy in eradicating leukemia, I witnessed face-to-face their suffering from the long-term consequence of graft-versus-host disease (GVHD). This experience was ultimately what drove me to engage in research to discover novel therapies. For this reason, I embarked on a PhD program in 2010 to design antibody therapy to (i) target GVHD and (ii) target hematological malignancies. Under the mentorship of Professor Hiromitsu Nakauchi at the University of Tokyo, an international leader in hematopoiesis, I developed allele-specific anti-human leukocyte antigen (HLA) monoclonal antibodies for severe GVHD caused by HLA-mismatched hematopoietic stem cell transplantation (Nakauchi et al., Exp Hematol, 2015). This study was the first to find that anti-HLA antibodies can be used therapeutically against GVHD. That success gave me the motivation and confidence to further my research beyond targeting GVHD, to targeting leukemic stem cells through my current postdoctoral fellowship in the laboratory of Professor Ravindra Majeti, Department of Hematology at Stanford University.
Many people suffer from leukemia each year, but we still don’t know how to completely cure it. Recent advances in sequencing technologies have tremendously improved our understanding of the underlying mutations that drive hematologic malignancies, although, the reality is that the majority of the mutations are not easily “druggable” and the discovery of these mutations has not yet made a significant impact in patient outcomes. I view this perhaps the most crucial challenges facing a translational cancer researcher like myself. My current research is a major step toward my long term goal to make personalized medicine a reality for patients with acute myeloid leukemia (AML) and other hematologic malignancies. Although my research is focused on targeting Ten-Eleven Translocation methylcytosine dioxygenase-2 (TET2) mutations, I anticipate it will lead to a better understanding of the cell context requirement for TET2 mutations in AML and help identify the critical cells to target to both prevent the development of de novo leukemia and halt relapse. It may also prove of value to understanding of the biology of a range of other cancers.