A5005754831- CAR-T cell therapy research
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- interferon and immune responses
- Cancer-related molecular mechanisms research
- Mesenchymal stem cell research
- Cancer Cells and Metastasis
- Cell death mechanisms and regulation
- Single-cell and spatial transcriptomics
- Advanced Breast Cancer Therapies
- PI3K/AKT/mTOR signaling in cancer
- Immunodeficiency and Autoimmune Disorders
- Long-Term Effects of COVID-19
- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- Circular RNAs in diseases
- Microtubule and mitosis dynamics
- Ferroptosis and cancer prognosis
- Ubiquitin and proteasome pathways
- Toxoplasma gondii Research Studies
- Diabetes and associated disorders
Harvard University
2017-2025
Brigham and Women's Hospital
2017-2025
Dana-Farber Cancer Institute
2021-2023
Broad Institute
2021-2023
Harvard Stem Cell Institute
2017-2021
Massachusetts Institute of Technology
2021
National Institute of Immunology
2012-2020
Massachusetts General Hospital
2017
Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Here, we generate distinct imageable syngeneic mouse GBM-tumor models and utilize RNA-sequencing, CyTOF correlative immunohistochemistry assess immune-profiles these models. We identify immunologically-inert -active syngeneic-tumor types show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells...
Abstract The coronavirus disease 2019 (COVID-19) pandemic has grown to be a global public health crisis with no safe and effective treatments available yet. Recent findings suggest that severe acute respiratory syndrome 2 (SARS-CoV-2), the pathogen causes COVID-19, could elicit cytokine storm drives edema, dysfunction of airway exchange, distress in lung, followed by cardiac injury thromboembolic events leading multiorgan failure death. Mesenchymal stem cells (MSCs), owing their powerful...
Posttranslational modifications (PTMs) can alter many fundamental properties of a protein. One or combinations them have been known to regulate the dynamics cellular pathways and consequently all vital processes. Understandably, pathogens evolved sophisticated strategies subvert these mechanisms achieve instantaneous control over host functions. Here, we present first report modulation by intestinal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) SUMOylation, PTM pathway...
Abstract Purpose: Despite tumor resection being the first-line clinical care for glioblastoma (GBM) patients, nearly all preclinical immune therapy models intend to treat established GBM. Characterizing cytoreductive surgery-induced response combined with administration of cytokines has potential offering a new treatment paradigm GBMs. Experimental Design: We developed syngeneic orthotopic mouse GBM and characterized intact resected tumors. also created highly secretable variant cytokine...
Activation of B and T lymphocytes leads to major remodelling the metabolic landscape cells enabling their post-activation functions. However, naive also show differences, genesis, nature functional significance these differences are not yet well understood. Here we that resting B-cells appeared have lower energy demands than T-cells as they consumed levels glucose fatty acids produced less ATP. Resting more dependent on OXPHOS, while dependence aerobic glycolysis. despite an apparently...
Abstract T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific cells or also alters responses at single level. Using brief (3 h) exposure TCR-transgenic mouse CD8 in vitro to varying densities cognate peptide-MHC followed by ligand-free culture IL-2, we found that determined frequencies but not expression levels early activation marker molecule, CD69. Cells low glucose...
Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by lack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment GBM patients. In this study, we show detection cell surface death receptor (DR) on CD146-enriched circulating tumor cells (CTC) captured from blood mice bearing patients diagnosed with GBM. Next, developed...
Amyloids are highly organized protein aggregates that arise from inappropriately folded versions of proteins or polypeptides under both physiological as well simulated ambiences. Once thought to be irreversible assemblies, amyloids have begun expose their more dynamic and reversible attributes depending upon the intrinsic properties precursor protein/peptide experimental conditions such temperature, pressure, structural modifications in proteins, presence chemicals reaction mixture. It has...
Summary Activated T‐cells make both interleukin‐2 (IL2) and its high‐affinity receptor component CD25. Regulatory CD4 (Treg cells) do not IL2, the IL2‐CD25 circuit is considered a paracrine crucial in their generation maintenance. Yet, all are capable of making IL2 at some stage during differentiation, cell‐intrinsic autocrine additionally possible. When we re‐visited experiments with mixed bone marrow chimeras using wide range ratios wild‐type (WT) IL2−/− genotype progenitors, found that,...
Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues. We report aif-hypomorphic harlequin (Hq) mice show thymic hypocellularity cell-autonomous thymocyte developmental block associated with apoptosis at the β-selection stage, independent of T receptor β recombination. No abnormalities are observed B lineage. Transgenes encoding wild-type or DNA-binding–deficient mutant Aif rectify defect, but transgene oxidoreductase...
Abstract Variability in cellular activation the immune system can have diverse consequences, resulting heterogeneity effector programming and function as well cell survival. While examining relationships between lymphocyte functionality, we find that apparently unimodally distributed coreceptor among naive T cells, simplistically expected to be due intrinsic noise, is not only correlated with major functional variation but modulated by extrinsic microenvironmental cues vivo. Thus, when cells...
PI3Kδ inhibitors are approved for the therapy of B cell malignancies, but their clinical use has been limited by unpredictable autoimmune toxicity, despite promising efficacy and evidence that toxicity is associated with improved outcomes. Prior phenotypic evaluation CyTOF identified increases in activated CD8 T cells activation Th17 cells, as well decreases Tregs, particularly patients toxicity. Here we sought to further understand effects idelalisib duvelisib vitro, demonstrate both can...
Supplemental Materials and Methods from Tumor Resection Recruits Effector T Cells Boosts Therapeutic Efficacy of Encapsulated Stem Expressing IFNβ in Glioblastomas
<p>Flow cytometry analysis of M1/M2 macrophage polarization post tumor resection and IFNβ treatment in CT2A bearing mouse brains</p>
<p>Engineering cells expressing secretory mouse and human IFNβ</p>
<p>Cell viability of human GBM cells in response to different doses hIFNβ</p>
<p>Flow cytometry analysis of immune cell population in CT2A tumor bearing mouse brains</p>