Monocytes provide defense against infection and serve as progenitors for tissue macrophages and dendritic cells. Recruitment of monocytes to sites of infection begins with trafflcl Our first aim i s to investigate Ly6Chi monocyte reconstitution and the localization and responsiveness of monocytes and MSCs following allo-HSCT. We will use CCR2 and MCP-1 reporter mice to investigate monocytes following allo-HSCT. We will use a conditional MCP-1 knockout mouse strain to determine the contribution of MSCs to the development ofthe inflammatory monocyte compartment.
Our second aim i s to determine the Impact of GvHD on monocyte trafficking and to determine the role of Ly6Chi monocytes in the development of GvHD. We will aiso quantify inflammatory monocyte numbers in patients following allo-HSCT and correlate circulating monocyte levels with subsequent development of GvHD.
Our third aim addresses our hypothesis that changes in the intestinal microbota following allo-HSCT influence monocyte emigration from bone marrow. We will investigate changes in the intestinal microbiota during allo- HSCT using high-throughput 16S rDNA sequencing and correlate changes in the intestinal microbiota with circulating inflammatory monocyte levels and activation. The studies described in this project will identify in vivo mechanisms that drive reconstitution ofthe monocyte compartment and will define the role of the intestinal microbiota in re-establishing immune homeostasis following allo-HSCT.

Public Health Relevance

Monocytes are a subset of blood cells that move from the bone marrow to tissues, where they can fight infections. The experiments we are proposing will determine which factors following bone marrow transplantation are important for optimal reconstitution of monocytes. These studies may lead to new approaches to minimize infections and graft versus host disease following transplantation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York
United States
Zip Code
Dao, Tao; Korontsvit, Tatyana; Zakhaleva, Victoria et al. (2017) An immunogenic WT1-derived peptide that induces T cell response in the context of HLA-A*02:01 and HLA-A*24:02 molecules. Oncoimmunology 6:e1252895
Peled, Jonathan U; Devlin, Sean M; Staffas, Anna et al. (2017) Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation. J Clin Oncol 35:1650-1659
Getta, Bartlomiej M; Roshal, Mikhail; Zheng, Junting et al. (2017) Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Is Associated with Favorable Outcomes in Mixed Phenotype Acute Leukemia. Biol Blood Marrow Transplant 23:1879-1886
Barba, Pere; Ratan, Ravin; Cho, Christina et al. (2017) Hematopoietic Cell Transplantation Comorbidity Index Predicts Outcomes in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Receiving CD34+ Selected Grafts for Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 23:67-74
Barba, Pere; Hilden, Patrick; Devlin, Sean M et al. (2017) Ex Vivo CD34+-Selected T Cell-Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease Biol Blood Marrow Transplant 23:452-458
Boudreau, Jeanette E; Giglio, Fabio; Gooley, Ted A et al. (2017) KIR3DL1/ HL A-B Subtypes Govern Acute Myelogenous Leukemia Relapse After Hematopoietic Cell Transplantation. J Clin Oncol 35:2268-2278
Ghosh, Arnab; Smith, Melody; James, Scott E et al. (2017) Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. Nat Med 23:242-249
Fischer, Julius C; Bscheider, Michael; Eisenkolb, Gabriel et al. (2017) RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury. Sci Transl Med 9:
Goldberg, Jenna D; Zheng, Junting; Ratan, Ravin et al. (2017) Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant. Leuk Lymphoma 58:1859-1871
Ito, Reiko; Hale, Laura P; Geyer, Susan M et al. (2017) Late Effects of Exposure to Ionizing Radiation and Age on Human Thymus Morphology and Function. Radiat Res 187:589-598

Showing the most recent 10 out of 435 publications