This Program Project Grant seeks continued support for investigations into the biology of hematopoietic cell transplantation (HCT) and the translation of concepts to the clinic to improve the outcomes for patients with serious hematological malignancies. The overarching hypothesis of this proposal is that cellular components are critical to transplantation biology and through the in depth understanding of the molecular and cellular events of discrete cell populations fundamental discoveries will be made which will have critical therapeutic implications. Although our clinical efforts are focused on patients with hematological malignancies the concepts developed have broad implications in many fields of biology and medicine extending to patients with malignancies, autoimmune disorders and undergoing solid organ transplantation. The investigators will focus on the major cellular components of the hematopoietic and immune systems including hematopoietic stem and progenitor cells, B, T, natural killer (NK), NK-T, regulatory and dendritic cell populations. The major events in HCT including stem cell engraftment, graft vs host disease (GVHD), graft vs tumor (GVT) reactions and immune reconstitution will be studied in detail. Clinical studies range from exploratory phase I/I I clinical trials to phase III definitive examinations of treatment strategies. We will build upon our success in the prior funding period where we have developed a novel non-myeloablative preparative regimen which results in consistent donor specific engraftment with maintained GVT effects with markedly reduced risk of GVHD. We will also extend the use of cellular products studied within the context of this Grant and successfully translated to the clinic. The proposal consists of 8 Projects and 4 supportive Cores which provide critical functions of administration, biostatistics and data management, molecular pathology and novel cellular imaging strategies and GMP laboratory services for cell product development and sample distribution. As a whole this integrated group of investigators will focus their efforts on critical issues of hematopoietic cell transplantation and cellular based therapeutics.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (O5))
Program Officer
Merritt, William D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Chen, Yi-Bin; Efebera, Yvonne A; Johnston, Laura et al. (2017) Increased Foxp3+Helios+ Regulatory T Cells and Decreased Acute Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation in Patients Receiving Sirolimus and RGI-2001, an Activator of Invariant Natural Killer T Cells. Biol Blood Marrow Transplant 23:625-634
Spinner, Michael A; Fernández-Viña, Marcelo; Creary, Lisa E et al. (2017) HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity. Blood Adv 1:1347-1357
Costa, Helio A; Neal, Joel W; Bustamante, Carlos D et al. (2017) Identification of a Novel Somatic Mutation Leading to Allele Dropout for EGFR L858R Genotyping in Non-Small Cell Lung Cancer. Mol Diagn Ther 21:431-436
Xu, Liwen; You, Xiaoqing; Zheng, PingPing et al. (2017) Methodologic Considerations in the Application of Next-Generation Sequencing of Human TRB Repertoires for Clinical Use. J Mol Diagn 19:72-83
Du, Jing; Paz, Katelyn; Thangavelu, Govindarajan et al. (2017) Invariant natural killer T cells ameliorate murine chronic GVHD by expanding donor regulatory T cells. Blood 129:3121-3125
Paul, Jed; Sahaf, Bita; Perloff, Spenser et al. (2016) High-throughput allogeneic antibody detection using protein microarrays. J Immunol Methods 432:57-64
Ozawa, Michael G; Bhaduri, Aparna; Chisholm, Karen M et al. (2016) A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma. Mod Pathol 29:1212-20
Kelley, Todd W; Arber, Daniel A; Gibson, Christine et al. (2016) Template for Reporting Results of Biomarker Testing of Specimens From Patients With Myeloproliferative Neoplasms. Arch Pathol Lab Med 140:675-7
Sen, Nandini; Arvin, Ann M (2016) Dissecting the Molecular Mechanisms of the Tropism of Varicella-Zoster Virus for Human T Cells. J Virol 90:3284-7
Khodadoust, M S; Luo, B; Medeiros, B C et al. (2016) Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia. Leukemia 30:947-50

Showing the most recent 10 out of 304 publications