A5001446861- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Advancements in Semiconductor Devices and Circuit Design
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Silicon Carbide Semiconductor Technologies
- Exercise and Physiological Responses
- Genomics and Chromatin Dynamics
- Nanowire Synthesis and Applications
- Muscle activation and electromyography studies
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
Stanford University
2021-2025
Gladstone Institutes
2022-2024
A major limitation of chimeric antigen receptor (CAR) T cell therapies is the poor persistence these cells in vivo
Chronic stimulation can cause T cell dysfunction and limit the efficacy of cellular immunotherapies. Improved methods are required to compare large numbers synthetic knockin (KI) sequences reprogram functions. Here, we developed modular pooled KI screening (ModPoKI), an adaptable platform for construction DNA libraries using barcoded multicistronic adaptors. We built two ModPoKI 100 transcription factors (TFs) 129 natural surface receptors (SRs). Over 30 screens across human TCR- CAR-T cells...
Immune checkpoint blockade can facilitate tumor clearance by T cells, resulting in long term patient survival. However, the capacity of exhausted CD8 + cells (Tex), present during chronic antigen exposure, to form memory after remains unclear. Here, we performed longitudinal single cell RNA/T receptor sequencing and ATAC-sequencing on antigen-specific lymphocytic choriomeningitis virus (LCMV) infection. These data revealed formation a robust population that transcriptionally, epigenetically,...
Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals any age who have been inactive for prolonged period or immobilization. Additionally, acute diseases such as COVID-19 sequelae and exacerbate wasting, leading to additional fatigue symptoms. It necessary investigate potent functional nutrients reinforcement both disuse ensure better physical performance.The effects Sanghuangporus sanghuang SS-MN4 mycelia were tested on two groups 6-week-old male mice-one with...
Poor CAR T persistence limits cell therapies for B malignancies and solid tumors
Abstract 3-dimensional (3D) genome conformation is central to gene expression regulation, yet our understanding of its contribution rapid transcriptional responses, signal integration, and memory in immune cells limited. Here, we study the molecular regulation inflammatory response primary macrophages using integrated transcriptomic, epigenomic, chromosome data, including base pair-resolution Micro-Capture C. We demonstrate that interleukin-4 (IL-4) primes by stably rewiring 3D conformation,...
Abstract Protein-coding genes in the human genome evolved via modular rearrangement of domains from ancestral 1 . Here, we develop a scalable, evolutionarily guided method to assemble novel protein-coding constituent within protein family, termed DESynR (Domain Engineered Synthesis and Recombination) genes. Using primary chimeric antigen receptor T cells as model system, find that expression Activator Protein-1 (AP-1) transcription factors (TFs) significantly outperforms overexpression...
Summary Cell cycle (CC) is a fundamental biological process with robust, cyclical gene expression programs to facilitate cell division. In the immune system, productive response requires expansion of pathogen-responsive types, but whether CC also confers unique that inform subsequent immunological remains unclear. Here we demonstrate single macrophages adopt different plasticity states in CC, which major source heterogeneity polarizing cytokines. Specifically, macrophage interferon gamma...