A5053083873- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Multiple Myeloma Research and Treatments
- Acute Myeloid Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Immune cells in cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Acute Lymphoblastic Leukemia research
- Chemokine receptors and signaling
- Malaria Research and Control
- Renal Transplantation Outcomes and Treatments
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mesenchymal stem cell research
- RNA Interference and Gene Delivery
- Research on Leishmaniasis Studies
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
- Eosinophilic Disorders and Syndromes
Fred Hutch Cancer Center
2018-2025
Translational Therapeutics (United States)
2025
QIMR Berghofer Medical Research Institute
2015-2024
University of Washington Medical Center
2018-2024
University of Washington
2019-2024
The Royal Melbourne Hospital
2024
Seattle Children's Hospital
2023
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2019-2023
City Of Hope National Medical Center
2023
Emory University
2023
Cell surface mucin glycoproteins are highly expressed by all mucosal tissues, yet their physiological role is currently unknown. We hypothesized that cell mucins protect cells from infection. A rapid progressive increase in gastrointestinal expression of 1 (Muc1) followed infection mice with the bacterial pathogen Campylobacter jejuni. In first week following oral infection, C. jejuni was detected systemic organs vast majority Muc1–/– but never Muc1+/+ mice. Although entered epithelial both...
Chronic GVHD (cGVHD) is the major cause of late, nonrelapse death following stem cell transplantation and characteristically develops in organs such as skin lung. Here, we used multiple murine models cGVHD to investigate contribution macrophage populations development cGVHD. Using an established IL-17-dependent sclerodermatous model, confirmed that macrophages infiltrating are derived from donor bone marrow (F4/80+CSF-1R+CD206+iNOS-). Cutaneous developed a CSF-1/CSF-1R-dependent manner,...
Oncogenic JAK mutation sensitizes myeloproliferative neoplasms to immune checkpoint inhibition.
Worldwide, each year over 30,000 patients undergo an allogeneic hema-topoietic stem cell transplantation with the intent to cure high-risk hematologic malignancy, immunodeficiency, metabolic disease, or a life-threatening bone marrow failure syndrome. Despite substantial advances in donor selection and conditioning regimens greater availability of allograft sources, transplant recipients still endure morbidity mortality graft-versus-host disease (GVHD). Herein, we identify key aspects acute...
Donor T cell responses to host alloantigen are known predictors for graft-versus-host disease (GVHD); however, the effect of donor responsiveness an inflammatory stimulus such as lipopolysaccharide (LPS) on GVHD severity has not been investigated. To examine this, we used mouse strains that differ in their sensitivity LPS donors experimental bone marrow transplant (BMT) system. Lethally irradiated (C3FeB6)F1 hosts received BMT from either LPS-sensitive (LPS-s) C3Heb/Fej, or LPS-resistant...
Acute graft-versus-host disease (GVHD) and leukemic relapse remain the two major obstacles to successful outcomes after allogeneic bone marrow transplantation (BMT). Recent studies have demonstrated that loss of gastrointestinal tract integrity, specifically translocation LPS into systemic circulation, is critical induction cytokine dysregulation contributes GVHD. Using a mouse BMT model, we studied effects direct antagonism on GVHD severity graft-versus-leukemia (GVL) activity....
Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor H antigen barriers (survival at day 50: 90 vs 20%, P < 0.001). Surpisingly, administration polarized the donor T cell cytokine responses to host after BMT with 50% reduction IFNgamma IL-2 secretion 10-fold increase IL-4. This polarization was associated reduced serum levels decreased IL-12 production mixed lymphocyte cultures (MLC). In...
We demonstrate an increase in graft-versus-host disease (GVHD) after experimental bone marrow transplant (BMT) when cyclophosphamide (Cy) is added to otherwise well-tolerated dose (900 cGy) of total body irradiation (TBI). Donor T cell expansion on day +13 was increased conditioning with Cy/TBI compared Cy or TBI alone, although cytotoxic lymphocyte (CTL) function not altered. Histological analysis the gastrointestinal tract demonstrated synergistic damage by and allogeneic donor cells,...
Effective immunity requires the coordinated activation of innate and adaptive immune responses. Natural killer (NK) cells are central effectors, but can also affect generation acquired responses to viruses malignancies. How NK influence efficacy immunity, however, is poorly understood. Here, we show that negatively regulate duration effectiveness virus-specific CD4+ CD8+ T cell by limiting exposure infected antigen-presenting cells. This impacts quality ability limit viral persistence. Our...
Abstract The lineage of dendritic cells (DC), and in particular their relationship to monocytes macrophages, remains obscure. Furthermore, the requirement for macrophage growth factor CSF-1 during DC homeostasis is unclear. Using a transgenic mouse which promoter CSF-1R (c-fms) directs expression enhanced GFP myeloid lineage, we determined that although c-fms inactive precursors, it up-regulated all subsets differentiation. plasmacytoid CD11chigh are reduced by 50–70% CSF-1-deficient...
CD4(+)CD25(+) regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms Treg suppression vitro have been described, by which modulate CD8(+) cell differentiation and effector function vivo are more poorly defined. It has proposed, instances, that modulation cytokine homeostasis could be an important mechanism regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate Treg, critically regulating IL-2...