A5001592487- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Gene expression and cancer classification
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- MicroRNA in disease regulation
- Monoclonal and Polyclonal Antibodies Research
- Gene Regulatory Network Analysis
- Viral gastroenteritis research and epidemiology
- Cell Image Analysis Techniques
Yale University
2020-2025
University of Massachusetts Amherst
2017-2019
Tumor-specific CD8 + T cells in stable tumor-draining lymph node reservoir are clonally and developmentally related to those tumors.
Naïve CD8 T cells have the potential to differentiate into a spectrum of functional states during an immune response. How these developmental decisions are made and what mechanisms exist suppress differentiation toward alternative fates remains unclear. We employed in vivo CRISPR-Cas9–based perturbation sequencing assess role ~40 transcription factors (TFs) epigenetic modulators cell fate decisions. Unexpectedly, we found that knockout TF Klf2 resulted aberrant exhausted-like acute...
The differentiation of naive CD8 T cells into effector cytotoxic lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe dual role the let-7 microRNAs in regulation cell responses, where maintenance phenotype requires high levels expression, while generation depends receptor-mediated downregulation. Decrease expression activated enhances clonal expansion acquisition function through derepression...
The persistent murine norovirus strain MNVCR6 is a model for human and enteric viral persistence. causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although induces functional MNV-specific CD8+ T these lymphocytes fail to clear infection. To examine how cells promote immune escape, we interrogated cell interactions with adoptively transferring JEDI (just EGFP death inducing) into Gfi1b-GFP reporter mice. Unexpectedly, some partially...
Kras-driven lung adenocarcinoma (LUAD) is the most common cancer. A significant fraction of patients with LUAD respond to immunotherapy, but mechanistic studies immune responses against have been limited because a lack immunotherapy-responsive models. We report development immunogenic KP × NINJA (inversion inducible joined neoantigen) (KP-NINJA) model. This model allows temporal uncoupling antigen and tumor induction, which one wait until after infection-induced inflammation has subsided...
Maintaining the diversity and constant numbers of naïve T cells throughout organism's lifetime is necessary for efficient immune responses. Naïve cell homeostasis, which consists prolonged survival, occasional proliferation enforcement quiescence, tightly regulated by multiple signaling pathways are in turn controlled various transcription factors. However, full understanding molecular mechanisms underlying maintenance peripheral pool has not been achieved. In present study, we demonstrate...
Abstract “Stem-like” TCF1 + CD8 T cells (T SL ) are necessary for long-term maintenance of cell responses and the efficacy immunotherapy but, as tumors contain signals that should drive T-cell terminal-differentiation, how these maintained in remains unclear. We found a small number tumor-specific were present throughout development. Yet, most intratumoral differentiated progressed, corresponding with an immunologic shift tumor microenvironment (TME) from “hot” to “cold”. By contrast,...
CD4+ T follicular helper (TFH) cells provide help to B cells, which is critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer unclear. We found TFH correlated with GC and prolonged survival lung adenocarcinoma (LUAD) patients. To investigate further, we developed an LUAD model, tumor expressed B-cell- T-cell-recognized neoantigens. Interactions between tumor-specific were necessary control, as effector CD8+ cells. The latter reduced absence...
In single-cell sequencing analysis, several computational methods have been developed to map the cellular state space, but little has done or create embeddings of gene space. Here, we formulate embedding problem, design tasks with simulated data evaluate representations, and establish ten relevant baselines. We then present a graph signal processing approach call {\em pattern analysis} (GSPA) that learns rich representations from using dictionary diffusion wavelets on cell-cell graph. GSPA...
Abstract CD4 + T follicular helper (TFH) cells provide help to B cells, which is critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer unclear. We found TFH correlated with GC and prolonged survival lung adenocarcinoma (LUAD) patients. To investigate further, we developed an LUAD model, tumor expressed B-cell- T-cell-recognized neoantigens. Interactions between tumor-specific were necessary control, as effector CD8 cells. The latter reduced...
Kras-driven lung adenocarcinoma (LUAD) is one of the most common forms cancer. A significant fraction patients with LUAD respond to immunotherapy, but mechanistic studies immune responses against have been limited because a lack immunotherapy-responsive models. The Kras-Lox-STOP-Lox-G12D p53 flox/flox (KP) model faithfully recapitulates human does not elicit tumor-specific T cell developing tumors neoantigens. In vivo lentiviral transduction has used express neoantigens in KP LUADs this...
Abstract Although immunotherapy with PD-1/PD-L1 antagonists has significantly advanced patient care, the majority of cancer patients currently do not benefit from checkpoint inhibitor therapies. To identify novel targets for treatment PD-1 insensitive cancers, we developed a Immune-CRISPRomicsTM platform that enabled genome-wide CRISPR/Cas9 screens in primary T cells an vivo setting. Notably, screen identified clinically active molecules, such as and also predicted recent clinical failures....