A5008144438- Lymphatic System and Diseases
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Sympathectomy and Hyperhidrosis Treatments
- Cancer Cells and Metastasis
- Angiogenesis and VEGF in Cancer
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Cancer, Hypoxia, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Vascular Malformations and Hemangiomas
- Galectins and Cancer Biology
- Single-cell and spatial transcriptomics
- TGF-β signaling in diseases
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Caveolin-1 and cellular processes
- Cancer-related gene regulation
- Corneal Surgery and Treatments
New York University
2021-2024
Medpace (United States)
2024
NYU Langone Health
2022-2023
Oregon Health & Science University
2019-2023
Nebraska Medical Center
2014-2017
University of Nebraska Medical Center
2013-2017
Boys Town National Research Hospital
2011
Boys Town
2011
Lymphatic vessels are often considered passive conduits that flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests lymphatic actively regulate diverse processes from antigen transport leukocyte trafficking dietary lipid absorption. Here we tested the hypothesis infection-induced changes in contribute innate host defense. We demonstrate cutaneous vaccinia virus infection by scarification activates dermal capillary junction tightening...
Transmembrane mucins, MUC4 and MUC16 are associated with tumor progression metastatic potential in human pancreatic adenocarcinoma. We discovered that miR-200c interacts specific sequences within the coding sequence of mRNAs, evaluated regulatory nature this association. Pancreatic cancer cell lines S2.028 T3M-4 transfected showed a 4.18 8.50 fold down regulation mRNA, 4.68 4.82 mRNA compared to mock-transfected cells, respectively. A significant reduction glycoprotein expression was also...
MUC1 interacts with β-catenin and p120 catenin to modulate WNT signaling. We investigated the effect of overexpressing on regulation cyclin D1, a downstream target for WNT/β-catenin signaling pathway, in two human pancreatic cancer cell lines, Panc-1 S2-013. observed significant enhancement activation D1 promoter-reporter activity poorly differentiated Panc1.MUC1F cells that overexpress recombinant relative Panc-1.NEO cells, which express very low levels endogenous MUC1. In stark contrast,...
Tissue resident memory T cells (T
The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied two cardinal signs inflammation–pain swelling–by investigating molecular neural lymphatic vessel remodeling during corneal inflammation. A mouse model wound recovery was developed to study this process vivo. Administration nerve growth factor (NGF) increased pain sensation inhibited regression...
Leukocyte egress from peripheral tissues to draining lymph nodes is not only critical for immune surveillance and initiation but also contributes the resolution of tissue responses. While a variety methods are used quantify leukocyte non-lymphoid, tissues, cellular molecular mechanisms that govern context-dependent remain poorly understood. Here, we describe use in situ photoconversion quantitative analysis murine skin tumors. Photoconversion allows direct labeling leukocytes resident within...
The MUC1 glycoprotein is overexpressed and aberrantly glycosylated in >90% of pancreatic ductal adenocarcinoma cases impacts tumor progression by initiating downstream signaling through phosphorylation its cytoplasmic tail. Previous studies have demonstrated that alters expression known targets activator protein 1 (AP-1); however, no evaluated the precise impact on activity formation AP-1. Given role these proteins modulating migration, invasion, progression, we explored effects AP-1 dimer...
Introduction Quantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms tissue structures that determine distribution within around nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates blood lymphatic vessels (lymphovasculature) also dictate trafficking...
Purpose: To determine whether glucocorticoids suppress corneal lymphatic vessel growth (lymphangiogenesis) or induce regression. Methods: We measured human endothelial cell proliferation and collagen-induced tubulogenesis in culture conditions with without dexamethasone, a potent glucocorticoid. developed modification of the mouse suture model that allowed us to visualize (with suture) regression (suture removed) using immunofluorescence microscopic techniques. administered dexamethasone...
Leukocyte egress from peripheral tissues to draining lymph nodes is not only critical for immune surveillance and initiation but also contributes the resolution of tissue responses. While a variety methods are used quantify leukocyte non-lymphoid, tissues, cellular molecular mechanisms that govern context-dependent remain poorly understood. Here, we describe use in situ photoconversion quantitative analysis murine skin tumors. Photoconversion allows direct labeling leukocytes resident within...
Abstract The processes of intra- and extravasation tumor cells into out the blood lymphatic systems are crucial steps during metastasis to distant organ sites. These tightly regulated by initial binding sialyl Lewis A X (sialyl Le A/X) carbohydrate moeities found on adhesion protein E-selectin expressed activated endothelium. GMI-1271 is a small molecule glycomimetic rationally designed based bioactive conformation Lea/x potent specific antagonist E-selectin. In vitro treatment human...
Abstract The tumor microenvironment's cellular and molecular composition includes a complex matrix that encases cells presents conundrum in respect to pancreatic therapy. On one hand, the dense desmoplastic reaction accompanies growth of well differentiated tumors reduces blood flow creates an environment which it is difficult deliver therapies. other elimination certain stromal elements enhances aggressiveness metastatic potential cancer cells. Several current studies are attempting target...
Abstract T cell therapies have had modest efficacy in solid tumors due to their failure proliferate following infusion. We designed a mesothelin (MSLN) CAR product (OPB-101) which includes novel promoter (OP1), an optimized CAR, safety switch, and CD8α-targeted IL-2/15 cytokine promote expansion improve tumors. Human anti-MSLN binders were for the target using our OUTSPACERTM library. evaluation was conducted vitro coculture assays validated NSG tumor xenograft models. OUTSMARTTM avoid...
Abstract A major hurdle for chimeric antigen receptor (CAR) T cells to function in solid tumors is chronic exposure leading terminal lymphocyte exhaustion and impaired anti-tumor activity. Therefore, it necessary establish improved vitro models of antigen-driven CAR cell evaluate new design candidates prior validation with costly vivo studies. Using the human tumor mesothelin (MSLN) MSLN-targeting as a model, we developed two assays that drive an exhausted phenotype can be used predict...
<h3>Background</h3> T cell therapies have shown modest efficacy in solid tumors, including ovarian cancer, due to limited functional persistence. OPB-101 consists of an optimized mesothelin (MSLN) CAR, a CD8α-targeted IL-2 designed cytokine promote expansion, and improved EGFR safety switch. These transgenes are controlled by novel promoter that prevents exhaustion inducibly produces at the site tumor. <h3>Methods</h3> The MSLN CAR humanized anti-MSLN scFv optimal spacer from our OUTSPACER™...
Abstract Antigen-specific CD8 + T cell accumulation in tumors is a prerequisite for effective immunotherapy, and yet, the mechanisms of lymphocyte transit remain poorly defined. We find that tumor-associated lymphatic vessels control exit from via chemokine CXCL12, intratumoral antigen encounter tunes CXCR4 expression on effector cells. Only high affinity downregulates upregulates CXCL12 decoy receptor, ACKR3, thereby reducing sensitivity promoting retention. A diverse repertoire functional...