A5015082362- RNA Interference and Gene Delivery
- Ultrasound and Hyperthermia Applications
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Radiopharmaceutical Chemistry and Applications
- Cancer Cells and Metastasis
- Microbial Inactivation Methods
- Radiomics and Machine Learning in Medical Imaging
- Barrier Structure and Function Studies
- Viral gastroenteritis research and epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Medical Imaging and Pathology Studies
- Peptidase Inhibition and Analysis
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Cancer, Hypoxia, and Metabolism
- bioluminescence and chemiluminescence research
- Pancreatic and Hepatic Oncology Research
- Viral Infectious Diseases and Gene Expression in Insects
- Photoacoustic and Ultrasonic Imaging
Stanford University
2020-2024
Palo Alto University
2020-2024
Stratford University
2022-2024
Robust cytotoxic T cell infiltration has proven to be difficult achieve in solid tumors. We set out develop a flexible protocol efficiently transfect tumor and stromal cells produce immune-activating cytokines, thus enhance while debulking mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores are created facilitate controllable local transfection. Here, we applied substantially lower transmission frequency (250 kHz) than previously. The resulting microbubble...
Abstract The development of transgenic mouse models that express genes interest in specific cell types has transformed our understanding basic biology and disease. However, generating these is time- resource-intensive. Here we describe a model system, SELective Expression Controlled Transduction In Vivo (SELECTIV), enables efficient expression transgenes by coupling adeno-associated virus (AAV) vectors with Cre-inducible overexpression the multi-serotype AAV receptor, AAVR. We demonstrate...
Abstract High‐dimensional immunoprofiling is essential for studying host response to immunotherapy, infection, and disease in murine model systems. However, the difficulty of multiparameter panel design combined with a lack existing tools has prevented comprehensive study all major leukocyte phenotypes single assay. Herein, we present 40‐color flow cytometry deep immunophenotyping lymphoid tissues, including spleen, blood, Peyer's patches, inguinal lymph nodes, bone marrow, thymus. This uses...
Abstract Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, tunable strategy of multiple endogenous genes both vitro vivo, utilizing ultrasound as stimulus. By engineering hyper-efficient dCas12a effector under heat shock promoter, demonstrate system that can be inducibly activated through thermal energy produced by absorption. This allows versatile induction activation or...
Rationale: Despite recent advances in the use of adeno-associated viruses (AAVs) as potential vehicles for genetic intervention central and peripheral nervous system-associated disorders, gene therapy treatment neuropathology adults has not been approved to date.The currently FDA-approved AAV-vector based therapies rely on naturally occurring serotypes, such AAV2 or AAV9, which display limited no transport across blood-brain barrier (BBB) if systemically administered.Recently developed...
Immunotherapy is an important cancer treatment strategy; nevertheless, the lack of robust immune cell infiltration in tumor microenvironment remains a factor limiting patient response rates. In vivo gene delivery protocols can amplify responses and sensitize tumors to immunotherapies, yet non-viral transfection methods often sacrifice transduction efficiency for improved safety tolerance. To improve efficiency, we optimized strategy employing low ultrasound transmission frequency-induced...
Background: Although combination immunotherapies incorporating local and systemic components have shown promising results in treating solid tumors, varied tumor microenvironments (TMEs) can impact immunotherapeutic efficacy. Method: We designed evaluated treatment strategies for breast pancreatic cancer combining magnetic resonance-guided focused ultrasound (MRgFUS) ablation antibody therapies. With a of single-cell sequencing, spectral flow cytometry, histological analyses, we profiled an...
Abstract Introduction: Adoptive cell transfer (ACT) of T cells has emerged in recent years as a powerful immunotherapy against cancer. Currently, are harvested from the patient or donor and genetically modified ex vivo to enhance their cancer-fighting capabilities. However, this process is costly more complex than administering off-the-shelf therapies such small molecule drugs monoclonal antibodies. The development methods transfect remains an important endeavor for immunotherapies....
We apply spatial transcriptomics and proteomics to select pancreatic cancer surface receptor targets for molecular imaging theranostics using an approach that can be applied many cancers. Selected surfaceome epithelial markers were spatially correlated provided specific localization, whereas the correlation between immune-cell or fibroblast was low. While of cancer-associated fibroblasts integrins has been proposed cancer, our data point tight junction protein claudin-4 as a theranostic...
Abstract Introduction: High-dimensional immunoprofiling is essential for studying host response to cancer immunotherapy. Synergistic agents often induce systemic changes in leukocyte abundance/function due targeting, dosage, or delivery, necessitating multi-tissue analyses decipher immune mechanisms. We set out dissect composition lymphoid tissues and tumors by using spectral cytometry, a multiplexed, high-throughput technology. Methods: engineered 40-color flow cytometry panel...
Abstract There is a critical need to develop new imaging and therapeutic strategies for pancreatic cancer. Current positron emission tomography (PET) assessments of ductal adenocarcinoma (PDAC) rely on 18F-FDG as radiopharmaceutical. To increase the sensitivity PDAC detection, we identified Claudin-4 (CLDN4), tight junction transmembrane protein, biomarker through spatial transcriptomic proteomic analyses. CLDN4 expression has previously been reported be enhanced in 99% primary 100%...
Abstract Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough in immunotherapy, offering promising outcomes the management of hematological malignancies. Current CAR-T vitro manufacturing routes involve T isolation, purification, activation, gene transduction and expansion. The process duration costs present significant barriers. Therefore, there is need for innovative strategies to address these concerns. Herein, we developed lipid nanoparticles (LNPs) deliver CAR-mRNA...
Molecular imaging using positron emission tomography (PET) provides sensitive detection and mapping of molecular targets. While cancer-associated fibroblasts integrins have been proposed as targets for pancreatic ductal adenocarcinoma (PDAC), herein, spatial transcriptomics proteomics human surgical samples are applied to select PDAC We find that selected cancer cell surface markers spatially correlated provide specific localization, whereas the correlation between immune-related or...
Abstract The tumor microenvironment (TME) subtype is a critical factor when combining immunotherapy with debulking strategies such as ultrasound ablation. To understand the effects of TME subtype, we studied two multi-site murine cancer models, an immune-suppressed KPC (Kras+/LSL-G12D; Trp53+/LSL-R172H; Pdx1-Cre) pancreatic adenocarcinoma (MT4) model and neu deletion HER2+ (NDL) mammary larger naïve lymphocyte population. After profiling models histology single-cell sequencing, designed...
Microbubble-mediated DNA vaccination is applied to treat NDL murine breast cancer. With an optimized microbubble and ultrasound protocol, the transfection efficiency increased. Immune cell recruitment tumor microenvironment then enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokines, leading regression. This reported Katherine W. Ferrara co-workers in article number 2100033.