- CAR-T cell therapy research
- Cell Image Analysis Techniques
- Connective tissue disorders research
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Angiogenesis and VEGF in Cancer
- Tissue Engineering and Regenerative Medicine
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Advanced Biosensing Techniques and Applications
- Cellular Mechanics and Interactions
- Electrospun Nanofibers in Biomedical Applications
- Peptidase Inhibition and Analysis
- Radiomics and Machine Learning in Medical Imaging
- Elasticity and Material Modeling
- Melanoma and MAPK Pathways
- Advanced Fluorescence Microscopy Techniques
- CRISPR and Genetic Engineering
- Characterization and Applications of Magnetic Nanoparticles
- Phagocytosis and Immune Regulation
- Gene expression and cancer classification
- Lung Cancer Research Studies
- Pleural and Pulmonary Diseases
Molecular Oncology (United States)
2020
Boston University
2007-2011
Abstract Antiangiogenic therapies that target the VEGF pathway have been used clinically to combat cancer for over a decade. Beyond having direct impact on blood vessel development and tumor perfusion, accumulating evidence indicates these agents also affect antitumor immune responses. Numerous clinical trials combining antiangiogenic drugs with immunotherapies treatment of are ongoing, but mechanistic understanding how disruption angiogenesis may immunity is not fully discerned. Here, we...
Diverse biological roles for mitogen-activated protein kinase 4 (MAP4K4) have necessitated the identification of potent inhibitors in order to study its function various disease contexts. In particular, compounds that can be used carry out such studies vivo would critical elucidating potential therapeutic intervention. A structure-based design effort coupled with property-guided optimization directed at minimizing ability cross into CNS led an advanced compound 13 (GNE-495) showed excellent...
ABSTRACT Optical pooled screening (OPS) is a highly scalable method for linking image-based phenotypes with cellular perturbations. However, it has thus far been restricted to relatively low-plex phenotypic readouts in cancer cell lines culture, due limitations associated situ sequencing (ISS) of perturbation barcodes. Here, we developed PerturbView, an OPS technology that leverages vitro transcription (IVT) amplify barcodes prior ISS, enabling screens multiplexed across diverse systems,...
Abstract Purpose: The purpose of this study is to determine how T cell engagers (TCEs) impact the localization and phenotype key T-cell subsets in preclinical solid tumor models. Background: TCEs are a class immunotherapy that have demonstrated substantial benefit patients with hematologic cancers shown evidence clinical activity malignancies. Mechanisms response TCEs, particularly tumors, not well understood. Identification diagnostic strategies stratify more likely respond expected enhance...
MAP4K4 inhibition augments CD8 T cell antitumor and antiviral responses.
Preclinical and clinical studies demonstrate that T cell-dependent bispecific antibodies (TDBs) induce systemic changes in addition to tumor killing, leading adverse events. Here, we report an in-depth characterization of acute responses TDBs tumor-bearing mice. Contrary modest tumors, rapid substantial lymphocyte accumulation endothelial cell (EC) activation occur around large blood vessels normal organs including the liver. We hypothesize organ-specific ECs may account for differential...
Mechanical failure of soft tissues is characteristic life-threatening diseases, including capillary stress failure, pulmonary emphysema, and vessel wall aneurysms. Failure occurs when mechanical forces are sufficiently high to rupture the enzymatically weakened extracellular matrix (ECM). Elastin, an important structural ECM protein, known stretch beyond 200% strain before failing. However, constructs native walls composed primarily elastin proteoglycans (PGs) have been found fail at much...
Enzyme activity plays an essential role in many physiological processes and diseases such as pulmonary emphysema. While the lung is constantly exposed to cyclic stretching, effects of stretch on mechanical properties extracellular matrix (ECM) during digestion have not been determined. We measured failure elastin-rich ECM sheets loaded with static or uniaxial (40% peak strain) elastase digestion. Quasistatic stress-strain measurements were taken 30 min The incremental stiffness decreased...
ABSTRACT Recent advancements in transcriptomics and proteomics have opened the possibility for spatially resolved molecular characterization of tissue architecture with promise enabling a deeper understanding biology either homeostasis or disease. The wealth data generated by these technologies has recently driven development wide range computational methods. These methods requirement advanced coding fluency to be applied integrated across full spatial omics analysis process thus presenting...
Abstract Background: Tertiary lymphoid structures (TLS) have recently shown association with improved outcomes for patients treated immunotherapy across several cancer types. But pathologist-led identification of TLS on routine hematoxylin and eosin (H&E) stained images is time-consuming & lacks standardization. We developed a deep learning (DL) approach to identify digitized H&E whole slide (WSI) non-small cell lung (NSCLC). also elucidate underlying identified biology by...
Meeting abstracts Melanoma is the most serious form of skin cancer, resulting in nearly 10,000 deaths per year US alone. Approximately 76,000 people are diagnosed with melanoma each year, and that number has been growing steadily over last 30 years. Tragically, affects younger
<div>Abstract<p>Antiangiogenic therapies that target the VEGF pathway have been used clinically to combat cancer for over a decade. Beyond having direct impact on blood vessel development and tumor perfusion, accumulating evidence indicates these agents also affect antitumor immune responses. Numerous clinical trials combining antiangiogenic drugs with immunotherapies treatment of are ongoing, but mechanistic understanding how disruption angiogenesis may immunity is not fully...
<div>Abstract<p>Antiangiogenic therapies that target the VEGF pathway have been used clinically to combat cancer for over a decade. Beyond having direct impact on blood vessel development and tumor perfusion, accumulating evidence indicates these agents also affect antitumor immune responses. Numerous clinical trials combining antiangiogenic drugs with immunotherapies treatment of are ongoing, but mechanistic understanding how disruption angiogenesis may immunity is not fully...
<p>Supplementary tables 1-4 and supplementary figures 1-8.</p>
<p>Supplementary tables 1-4 and supplementary figures 1-8.</p>
Topic: 20. Lymphoma Biology & Translational Research Background: Diffuse large B-cell lymphoma (DLBCL), the most common form of Non-Hodgkin’s Lymphoma, is very aggressive and heterogeneous. Up to 40% patients develop relapsed/refractory disease after standard treatment rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). Importantly, levels lymphocytes macrophages correlate with response R-CHOP, so ability accurately detect quantify these cells critical. However,...
Abstract Map4k4 is broadly expressed across different cell types and its function type context dependent. Although it in multiple of immune cells, specific subsets lymphocytes myeloid cells have yet to be determined. Here we demonstrate that reducing MAP4K4 activity can enhance CD8 T functions the anti-tumor anti-viral responses. Inducible deletion increases activation, proliferation, cytokine production, target killing vitro, enhances cell-mediated suppression tumor growth as well...