A5030843866- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Eosinophilic Esophagitis
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Enzyme-mediated dye degradation
- Microbial bioremediation and biosurfactants
- Influenza Virus Research Studies
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Epigenetics and DNA Methylation
- Invertebrate Immune Response Mechanisms
- Advanced Glycation End Products research
- Immune responses and vaccinations
- Tuberculosis Research and Epidemiology
- Inflammasome and immune disorders
- Wnt/β-catenin signaling in development and cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer Immunotherapy and Biomarkers
- Pharmaceutical and Antibiotic Environmental Impacts
- Cancer-related gene regulation
Imam Abdulrahman Bin Faisal University
2025
Epix Pharmaceuticals (United States)
2025
Tufts University
2023
Indiana University School of Medicine
2015-2020
Indiana University – Purdue University Indianapolis
2014-2020
Indiana University
2017-2018
Indiana University Health
2015-2017
Inserm
2010-2016
Centre de Physiopathologie de Toulouse-Purpan
2016
Indiana University Indianapolis
2015
Graft-versus-host disease (GVHD) remains a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We previously identified high plasma soluble suppression of tumorigenicity 2 (sST2) as biomarker the development GVHD and death. sST2 sequesters interleukin-33 (IL-33), limiting its availability to T cells expressing membrane-bound ST2 (mST2) [T helper (TH2) ST2(+)FoxP3(+) regulatory cells]. report that blockade in peritransplant period with neutralizing monoclonal...
Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic via graft-versus-leukemia (GVL) reactivity, transfer of these is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, also attack host normal tissues through the fatal graft-versus-host disease (GVHD). Full separation GVL activity from GVHD has yet to be achieved. Here, we show that, mice humans, a population interleukin-9 (IL-9)–producing activated...
Gastrointestinal graft-versus-host-disease (GI-GVHD) is a life-threatening complication occurring after allogeneic hematopoietic cell transplantation (HCT), and blood biomarker that permits stratification of HCT patients according to their risk developing GI-GVHD would greatly aid treatment planning. Through in-depth, large-scale proteomic profiling presymptomatic samples, we identified T population expressing both CD146, adhesion molecule, CCR5, chemokine receptor upregulated as early 14...
Gene therapy holds great promise for treating various congenital rare diseases. However, immunogenicity against viral vectors used in gene remains a challenge, impacting both the safety and efficacy of products. Neutralizing antibodies vector capsid proteins impact ability to re-dose patients, which growing body evidence suggests might be required some indications certain younger patient populations. In this communication, we report novel dual-acting liposomal formulation that induces immune...
Soluble cytokine receptors function as decoy to attenuate cytokine-mediated signaling and modulate downstream cellular responses. Dysregulated overproduction of soluble can be pathological, such ST2 (sST2), a prognostic biomarker in cardiovascular diseases, ulcerative colitis, graft-versus-host disease (GVHD). Although intervention using an antibody improves survival murine GVHD models, sST2 is challenging target for drug development because it binds IL-33 via extensive interaction...
Soluble stimulation-2 (ST2) is increased during graft-versus-host disease (GVHD), while Tregs that express ST2 prevent GVHD through unknown mechanisms. Transplantation of Foxp3- T cells and were collected sorted from different Foxp3 reporter mice indicated in developed GVHD, ST2+ thymus derived predominantly localized to the intestine. ST2-/- Treg transplantation was associated with reduced total intestinal frequency activation. versus WT transcriptomes showed decreased functional markers...
Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 phenotype is promoted by the interaction receptor ICOS on cells with ligand (ICOSL) dendritic (DCs). We performed multiparametric flow cytometry in cohort 156 HCT recipients conducted experiments aGVHD murine models to understand role ICOSL+ DCs. observed an increased frequency...
T-cell polyspecificity, predicting that individual T cells recognize a continuum of related ligands, implies multiple antigens can tolerize specific for given self-antigen. We previously showed in C57BL/6 mice part the CD4(+) repertoire myelin oligodendrocyte glycoprotein (MOG) 35-55 also recognizes neuronal antigen neurofilament medium (NF-M) 15-35. Such bi-specific are frequent and produce inflammatory cytokines after stimulation. Since recognizing two self-antigens would be expected to...
Acute graft-versus-host disease (aGVHD) hinders the efficacy of allogeneic hematopoietic cell transplantation (HCT). Plasma levels soluble membrane-bound ST2 (ST2) are elevated in human and murine aGVHD correlated to type 1 T cells response. signals through adapter protein MyD88. The role MyD88 during has yet be elucidated. We found that knocking out donor protected against independent IL-1R TLR4 signaling two HCT models. This protection was entirely driven by MyD88-/- CD4 cells....
Graft-versus-host disease (GVHD) remains the major barrier to success of allogeneic stem cell transplantation (SCT). We have reported that soluble suppression tumoriginicity 2 (ST2) measured in plasma post-SCT patients is a marker for risk therapy-resistant GVHD and death. ST2 member IL-1 receptor family whose sole known ligand IL-33. Soluble acts as decoy Thus, we hypothesized blockade will increase amount free IL-33 be able bind membrane on CD4+ T cells, driving them toward Th2 phenotype,...
Restricted accessAbstractFirst published online March 1, 2016St2 Blockade Reduces Sst2-Producing T Cells While Maintaining Protective Mst2-Expressing during Graft-Versus-Host DiseaseJ Zhang, A Ramadan, […], B Griesenauer, W Li, M Turner, R Kapur, H Hanenberg, S Paczesny, C Liu, Blazar, and I Tawara+8-8View all authors affiliationsVolume 64, Issue 4https://doi.org/10.1136/jim-2016-000120.69
Restricted accessAbstractFirst published online March 1, 2016Il-33/St2 Triggering of Il-9-Secreting T Cells: From Proteomics to TherapeuticsA Ramadan, J Zhang, […], M Abu Zaid, L Taylor, H O'Leary, R Kapur, Hanenberg, HE Broxmeyer, MH Kaplan, and S Paczesny+7-7View all authors affiliationsVolume 64, Issue 4https://doi.org/10.1136/jim-2016-000120.73
As one of the most validated immunotherapies to date, allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative option for high-risk hematological malignancies, particularly acute myeloid leukemia (AML). The immunotherapeutic activity allo-HCT known as graft-vs-leukemia (GVL) activity. However, GVL often accompanied by T-cell reactivity allo-antigens in normal host tissues, which leads graft-versus-host disease (GVHD), another major cause death after HCT. Therefore,...
Abstract Allogeneic hematopoietic cell transplantation (HCT) is the most potent curative therapy for cancers of bone marrow; however, graft-versus-host disease (GVHD) continues to be major limitation successful HCT, with mortality rates around 50%. Current strategies suppress GVHD also compromise beneficial graft-versus-tumor (GVT) activity. We have shown that elevated IL-33-sequestering soluble ST2 in plasma a risk factor severe GVHD. In addition, IL-9-secreting Th9 and Tc9 subsets higher...
Acute graft-versus-host disease (aGVHD) hinders the efficacy of allogeneic hematopoietic cell transplantation (allo-HCT). We found that plasma soluble suppression tumorigenicity 2 (sST2) predicted GVHD-related mortality in allo-HCT patients. Excess sST2 sequesters IL-33, shown to increase producing T cells (Th1/Th17) and decrease mST2 expressing (Th2/Tregs) at onset aGVHD. Blockade excess ST2 inverted these phenotypes. signals through adapter protein MyD88. Lack MyD88 CD4 Tconvs has been...