A5102946305- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Fibroblast Growth Factor Research
- Immunotherapy and Immune Responses
- Medical Imaging and Pathology Studies
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Lung Cancer Treatments and Mutations
- IL-33, ST2, and ILC Pathways
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- Effects of Radiation Exposure
- Eosinophilic Disorders and Syndromes
- Monoclonal and Polyclonal Antibodies Research
- Metastasis and carcinoma case studies
- Congenital Diaphragmatic Hernia Studies
- Cytomegalovirus and herpesvirus research
- Cancer Immunotherapy and Biomarkers
- Pancreatic function and diabetes
- Renal Transplantation Outcomes and Treatments
- Genetic factors in colorectal cancer
- Herbal Medicine Research Studies
- Streptococcal Infections and Treatments
- Childhood Cancer Survivors' Quality of Life
- Epigenetics and DNA Methylation
Memorial Sloan Kettering Cancer Center
2010-2018
Kettering University
2011-2015
Monash University
2005-2015
Medizinische Hochschule Hannover
2013
Florida College
2013
Brigham and Women's Hospital
2013
University of Florida
2013
The Royal Melbourne Hospital
2010
Brisbane School of Theology
1967
Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies human flora before initial onset have not been reported. Here, we demonstrate in murine recipients allogeneic bone marrow transplantation (BMT) that secondary to graft-versus-host disease (GVHD) is associated with major shifts composition microbiota. The microbiota, turn, can modulate severity inflammation. In mouse models GVHD, observed loss overall diversity expansion...
Treating neutropenic fever with broad-spectrum antibiotics after allogeneic hematopoietic stem cell transplant is associated an increase in graft-versus-host disease mice and humans.
Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection, or immunodepletion. However, the mechanisms governing this remain poorly understood. We detail such mechanism, centered on interleukin-22 (IL-22) and triggered by depletion CD4(+)CD8(+) double-positive thymocytes. Intrathymic levels IL-22 were increased insult, recovery was impaired in IL-22-deficient mice. IL-22, which signaled through epithelial cells promoted their...
The LMO2 oncogene causes a subset of human T cell acute lymphoblastic leukemias (T-ALL), including four cases that arose as adverse events in gene therapy trials. To investigate the cellular origin LMO2-induced leukemia, we used fate mapping to study mice which Lmo2 was constitutively expressed thymus. induced self-renewal committed cells more than 8 months before development overt T-ALL. These self-renewing retained capacity for differentiation but several genes typical hematopoietic stem...
BMP4 produced by endothelial cells promotes thymic regeneration after acute damage activating FOXN1 and its downstream targets.
Paradoxical to its importance for generating a diverse T cell repertoire, thymic function progressively declines throughout life. This process has been at least partially attributed the effects of sex steroids, and their removal promotes enhanced thymopoiesis recovery from immune injury. We show that one mechanism by which steroids influence is through direct inhibition in cortical epithelial cells (cTECs) Delta-like 4 (Dll4), Notch ligand crucial commitment differentiation progenitors...
Summary Clostridium septicum is the causative agent of spontaneous gas gangrene or atraumatic myonecrosis, a sudden and frequently fatal infection that increasingly associated with malignancy colon. Little known about disease process although focus virulence studies has been α‐toxin, pore‐forming cytolysin encoded by csa gene secreted as an inactive protoxin. Until now lack techniques for genetic manipulation C. hindered use molecular approaches to understand pathogenesis. By introducing...
Reduced tissue perfusion leading to ischemia is a central component of the pathogenesis myonecrosis caused by Clostridium perfringens. The C. perfringens α-toxin has been shown capable inducing these changes, but its potential synergy with perfringolysin O (θ-toxin) less well understood. Similarly, septicum highly virulent causative agent spontaneous gas gangrene, effect on microcirculation not examined. Therefore, aim this study was use intravital microscopy examine effects and functional...
Cytotoxic antineoplastic therapy is used to treat malignant disease but results in long-term immunosuppression postpubertal and adult individuals, leading increased incidence severity of opportunistic infections. We have previously shown that sex steroid ablation (SSA) reverses immunodeficiencies associated with age hematopoietic stem cell transplantation both autologous allogeneic settings. In this study, we assessed the effects SSA by surgical castration on T recovery young male mice...
Mechanisms underlying age-related defects within lymphoid-lineages remain poorly understood. We previously reported that sex steroid ablation (SSA) induced lymphoid rejuvenation and enhanced recovery from hematopoietic stem cell (HSC) transplantation (HSCT). herein show that, mechanistically, SSA induces by functionally enhancing both HSC self-renewal propensity for differentiation through intrinsic molecular changes. Our transcriptome analysis revealed further support of the bone marrow...
Abstract Total body irradiation (TBI) damages hematopoietic cells in the bone marrow and thymus; however, long-term effects of with aging remain unclear. In this study, we found that impact radiation on thymopoiesis mice varied by sex dose but, overall, remained suppressed for ≥12 mo after a single exposure. Male female showed dose-dependent reduction thymic cKit+ lymphoid progenitors was maintained throughout life. Damage to stem (HSCs) dependent, as little 0.5 Gy causing significant...
Age-associated changes of T and NK cell (T/NK) potential human hematopoietic stem cells are unknown. In this study, we enumerate characterize T/NK precursors among CD34(+)Lin(-) populations circulating in normal adult peripheral blood (PB) by a limiting-dilution assay using coculture with OP9-DL1 stroma expressing Notch 1 ligand, Delta-like 1. The frequency was found to decrease donor age, whereas the ratio precursor (NK/T ratio) increased suggesting that lymphoid differentiation PB...
Current strategies to suppress graft-versus-host disease (GVHD) also compromise graft-versus-tumor (GVT) responses. Furthermore, most experimental separate GVHD and GVT responses merely spare function without actually enhancing it. We have previously shown that endogenously expressed TNF-related apoptosis-inducing ligand (TRAIL) is required for optimal activity against certain malignancies in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order model a...
Efforts to limit GVHD mediated by alloreactive donor T cells after allogeneic bone marrow transplantation are limited a concomitant decrease in graft-versus-tumor (GVT) activity and increased possibilities of tumor relapse. Using novel approach, we adoptively transferred conventional expressing the transcription factor promyelocytic leukemia zinc finger (PLZF), which confers effector properties resembling invariant natural killer cells, such as copious production cytokines under suboptimal...
It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- radiation-related changes different subtypes circulating HSPCs among CD34-positive/lineage marker-negative (CD34 Lin−) cell 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating...
The relationships between commitments of dendritic cells (DCs) and T in human hematopoietic stem are not well understood. In this study, we enumerate characterize conventional DC plasmacytoid precursors association with cell thymus-derived types NK among CD34(+) progenitor (HPCs) circulating peripheral blood. By limiting-dilution analyses using coculture stroma expressing Notch1 ligand, the precursor frequencies (PFs) DCs HPCs were found to significantly correlate PFs, but healthy donors....