A5073600852- Cancer Cells and Metastasis
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune cells in cancer
- Aerosol Filtration and Electrostatic Precipitation
- Pancreatic and Hepatic Oncology Research
- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Preterm Birth and Chorioamnionitis
- Skin and Cellular Biology Research
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Neurogenetic and Muscular Disorders Research
- Cell Adhesion Molecules Research
- Phagocytosis and Immune Regulation
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Neonatal and fetal brain pathology
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Wnt/β-catenin signaling in development and cancer
Cold Spring Harbor Laboratory
2019-2025
Stony Brook School
2019-2024
Stony Brook University
2019-2024
Mount Saint Mary College
2019
St. Jude Children's Research Hospital
2016
Significance Carcinomas resist immunotherapy because T cells are absent from nests of cancer cells. The chemokine/chemokine receptor system, which regulates the migration immune cells, is a candidate for this impaired intratumoral accumulation Cancer in human pancreatic, colorectal, and breast cancers coated with chemokine CXCL12 form covalent heterodimers keratin-19. This coating was investigated using mouse model pancreatic that replicates immunological characteristics cancer. Mouse...
Abstract The exclusion of T cells causes immune escape pancreatic ductal adenocarcinoma (PDA). cell is mediated by the interaction between CXCR4 on and its ligand, CXCL12, which complexed to keratin-19 (KRT19) surface PDA cells. KRT19 secretion essential this process but unusual because lacks an endoplasmic reticulum (ER)-directing signal peptide (SP). By using biotinylation ER-restricted TurboID system a split-GFP assay in cells, we demonstrate that enters ER via “head” domain....
Pancreatic ductal adenocarcinoma (PDA) is a potentially lethal disease lacking effective treatments. Its immunosuppressive tumor microenvironment (TME) allows it to evade host immunosurveillance and limits response immunotherapy. Here, using the mouse KRT19-deficient (sgKRT19-edited) PDA model, we find that intratumoral accumulation of natural killer T (NKT) cells required establish an immunologically active TME. Mechanistically, NKT facilitate type I interferon (IFN) production initiate...
Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how adapt to these contrasting microenvironments remains unknown. Cancer-associated (CAF) mediate quiescence producing the chemokine CXCL12, which coats cancer cells suppress T-cell infiltration. We examined whether CAFs can also adopt an immune-promoting profile. Single-cell RNA sequencing of from mouse pancreatic adenocarcinomas identified a subpopulation with...
Intratumoral B cell responses are associated with more favorable clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). However, the antigens driving these largely unknown. We sought to discover by using single-cell RNA sequencing (scRNA-Seq) and immunoglobulin (Ig) of tumor-infiltrating immune cells from seven primary PDAC samples. identified activated T evidence germinal center reactions. Ig plasma (PC) clones expressing isotype-switched hyper-mutated Igs, suggesting...
Abstract How pancreatic ductal adenocarcinoma (PDA) cells stimulate CXCR4 to exclude T and resist cell checkpoint inhibitors is not known. Here, we find that CXCL12, the ligand for produced by cancer-associated fibroblast, “coats” human PDA colorectal cancer as covalent heterodimers with keratin 19 (KRT19). Modeling formation of heterodimer three proteins shows KRT19 binds CXCL12 transglutaminase-2 (TGM2), TGM2 converts reversible KRT19-CXCL12 complex into a heterodimer. We validate this...
Abstract Intratumoral B cell responses are associated with more favorable clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). However, the antigens driving these largely unknown. We sought to discover by using single-cell RNA sequencing (scRNA-Seq) and immunoglobulin (Ig) of tumor-infiltrating immune cells from seven primary PDAC samples. identified activated T evidence germinal center reactions. Ig plasma (PC) clones expressing isotype-switched hyper-mutated Igs, suggesting...
<div>Abstract<p>Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how adapt to these contrasting microenvironments remains unknown. Cancer-associated (CAFs) mediate quiescence producing the chemokine CXCL12, which coats cancer cells suppress T-cell infiltration. We examined whether CAFs can also adopt an immune-promoting profile. Single-cell RNA-sequencing of from mouse pancreatic adenocarcinomas...
<p>Figure S1, S2, S3</p>
<p>Figure S1, S2, S3</p>
<p>Figure S1, S2, S3</p>
<div>Abstract<p>Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how adapt to these contrasting microenvironments remains unknown. Cancer-associated (CAFs) mediate quiescence producing the chemokine CXCL12, which coats cancer cells suppress T-cell infiltration. We examined whether CAFs can also adopt an immune-promoting profile. Single-cell RNA-sequencing of from mouse pancreatic adenocarcinomas...
<p>Figure S1, S2, S3</p>
<div>Abstract<p>Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how adapt to these contrasting microenvironments remains unknown. Cancer-associated (CAF) mediate quiescence producing the chemokine CXCL12, which coats cancer cells suppress T-cell infiltration. We examined whether CAFs can also adopt an immune-promoting profile. Single-cell RNA sequencing of from mouse pancreatic adenocarcinomas...
<p>Figure S1, S2, S3</p>
<div>Abstract<p>Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how adapt to these contrasting microenvironments remains unknown. Cancer-associated (CAF) mediate quiescence producing the chemokine CXCL12, which coats cancer cells suppress T-cell infiltration. We examined whether CAFs can also adopt an immune-promoting profile. Single-cell RNA sequencing of from mouse pancreatic adenocarcinomas...
<p>Figure S1, S2, S3</p>
Regulation of gene expression occurs at multiple levels, including the removal non‐coding sequences from protein‐coding pre‐messenger RNA transcripts, commonly known as pre‐mRNA splicing. Correct requires high fidelity splicing, up to 15% mutations leading disease may be a result aberrant cystic fibrosis, spinal muscular atrophy (SMA) and some leukemias. Pre‐mRNA splicing is multistep process that several proteins RNAs for ATP hydrolysis, essential DEAD‐box such Prp5. Here we investigate...