A5009043926- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- COVID-19 Clinical Research Studies
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- Nanowire Synthesis and Applications
- Phagocytosis and Immune Regulation
- Plant Virus Research Studies
- Pluripotent Stem Cells Research
Yale University
2021-2025
Center for Systems Biology
2023-2025
Systems Biology Institute
2024
Yale New Haven Health System
2023
Yale Cancer Center
2023
Abstract Age is a major risk factor for severe coronavirus disease-2019 (COVID-19). Here, we interrogate the transcriptional features and cellular landscape of aging human lung. By intersecting these age-associated changes with experimental data on SARS-CoV-2, identify several factors that may contribute to heightened severity COVID-19 in older populations. The lung transcriptionally characterized by increased cell adhesion stress responses, reduced mitochondria replication. Deconvolution...
The pleiotropic effects of human disease and the complex nature gene-interaction networks require knock-in mice allowing for multiplexed gene perturbations. Here we describe a series with C57BL/6 background conditional or constitutive expression LbCas12a high-fidelity enhanced AsCas12a, which were inserted at Rosa26 locus. Cas12a in did not lead to discernible pathology enabled efficient genome engineering. We used retrovirus-based immune-cell engineering CD4+ CD8+ T cells, B cells...
Cas9 transgenic animals have drastically accelerated the discovery of novel immune modulators. But due to its inability process own CRISPR RNAs (crRNAs), simultaneous multiplexed gene perturbations using remains limited, especially by pseudoviral vectors. Cas12a/Cpf1, however, can concatenated crRNA arrays for this purpose. Here, we created conditional and constitutive LbCas12a knock-in mice. With these mice, demonstrated efficient editing surface protein knockdown within individual primary...
Chimeric antigen receptor (CAR) T cells are powerful therapeutics; however, their efficacy is often hindered by critical hurdles. Here, utilizing the endocytic feature of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) cytoplasmic tail (CT), we reprogram CAR function and substantially enhance CAR-T in vivo . with monomeric, duplex, or triplex CTLA-4 CTs (CCTs) fused to C-terminus exhibit a progressive increase cytotoxicity under repeated stimulation, accompanied reduced activation...
Checkpoint blockade immunotherapy is a potent class of cancer treatment, however, the complex immunosuppressive tumor microenvironment (TME) often requires multi-agent combinations to be effective. Current combination approaches are cumbersome, usually involving one-drug-at-a-time scheme. Here, we devise Multiplex Universal Combinatorial Immunotherapy via Gene-silencing (MUCIG), as versatile approach for combinatorial immunotherapy. We harness CRISPR-Cas13d efficiently target multiple...
Abstract The advancement of CRISPR gene editing technology, especially the development Cas9 knock-in mice, has significantly boosted functional discovery various genetics factors in diverse fields including genetics, genomics, immunology, and biology cancer. However, pleiotropic effects on human disease complex nature interaction networks require a mouse model capable simultaneous multiplexed perturbation. Here, we present generation applications Cre-dependent conditional constitutive...
<h3>Background</h3> Developing successful immunotherapies heavily relies on the identification of potent and specific targets, has been a longstanding challenge in field. It is thus essential to have versatile toolkits enabling efficient endogenous gene editing. The advancement Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology,<sup>1</sup> especially development Cas9 knock-in mice, significantly boosted functional discovery various genetics factors diverse fields...