A5078597691- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Cancer Immunotherapy and Biomarkers
- Advanced Biosensing Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Microtubule and mitosis dynamics
- Click Chemistry and Applications
- Metabolism, Diabetes, and Cancer
- Advanced biosensing and bioanalysis techniques
- Ferroptosis and cancer prognosis
- Extracellular vesicles in disease
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
Takeda (United States)
2025
Center for Systems Biology
2017-2021
Massachusetts General Hospital
2017-2021
Harvard University
2020
Tumor-associated macrophages (TAMs) are widely implicated in cancer progression, and TAM levels can influence drug responses, particularly to immunotherapy nanomedicines. However, it has been difficult quantify total numbers their dynamic spatiotemporal distribution a non-invasive translationally relevant manner. Here, we address this need by developing pharmacokinetically optimized,
Prodrug strategies that facilitate localized and controlled activity of small-molecule therapeutics can reduce systemic exposure improve pharmacokinetics, yet limitations in activation chemistry have made it difficult to assign tunable multifunctionality prodrugs. Here, we present the design application a modular caging strategy couples bioorthogonal cleavage with self-immolative linker an aliphatic anchor. This leverages recently discovered vivo catalysis by nanoencapsulated palladium...
Abstract Radiation sensitivity varies greatly between tissues. The transcription factor p53 mediates the response to radiation; however, abundance of protein does not correlate well with extent radiosensitivity across Given recent studies showing that temporal dynamics influence fate cultured cells in irradiation, we set out determine dynamic behavior and its impact on radiation vivo. We find radiosensitive tissues show prolonged signaling after radiation, while more resistant transient...
Abstract Background. High-throughput screening of immunotherapies is crucial for identifying promising candidates against various cancer indications and accelerating the pre-clinical development cell therapies. Two technologies have shown promise in quantifying therapy effectiveness: patient-derived organoid (PDO) models co-cultured with therapies, deep learning-based computer vision, which facilitates large-scale, automated image analysis to extract quantitative metrics treatment efficacy...
Interpreting how multicellular interactions in the tumor affect resistance pathways to BRAF and MEK1/2 MAPK inhibitors (MAPKi) remains a challenge. To investigate this, we profiled global ligand-receptor among stromal/immune cells from biopsies of MAPK-driven disease. MAPKi increased tumor-associated macrophages (TAMs) some patients, which correlated with poor clinical response, coamplified bidirectional tumor-TAM signaling via receptor tyrosine kinases (RTKs) including AXL, MERTK, their...
Background Anaplastic thyroid cancer (ATC) is aggressive with a poor prognosis, partly because of the immunosuppressive microenvironment created by tumor-associated macrophages (TAMs). Purpose To understand relationship between TAM infiltration, tumor vascularization, and corresponding drug delivery using ferumoxytol-enhanced MRI macrin in an ATC mouse model. Materials Methods tumors were generated 6-8-week-old female B6129SF1/J mice through intrathyroid injection to model orthotopic tumors,...
The receptor tyrosine kinase Mer (MERTK) is a promising drug target in cancer, where it can influence the metastasis-promoting signaling of both tumor cells and immune alike; however, no small molecule probes currently exist to selectively image Mer. In this work, we design synthesize selective near-infrared fluorescent molecular probe (MERi-SiR). Confocal microscopy metastases mice reveals predominant accumulation Mer-expressing tumor-associated macrophages.
Microtubules (MTs) mediate mitosis, directional signaling, and are therapeutic targets in cancer. Yet vivo analysis of cancer cell MT behavior within the tumor microenvironment remains challenging. Here we developed an imaging pipeline using plus-end tip tracking intravital microscopy to quantify dynamics live xenograft models. Among analyzed features, cells displayed higher coherent orientation along their major axes compared with 2D vitro cultures, distinct from 3D collagen gel cultures....
Abstract Cell‐to‐cell heterogeneity can substantially impact drug response, especially for monoclonal antibody (mAb) therapies that may exhibit variability in both delivery (pharmacokinetics) and action (pharmacodynamics) within solid tumors. However, it has traditionally been difficult to examine the kinetics of mAb at a single‐cell level manner enables controlled dissection target‐dependent ‐independent behaviors. To address this issue, here we developed an vivo confocal (intravital)...