A5012332252- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Adolescent and Pediatric Healthcare
- Gut microbiota and health
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- RNA regulation and disease
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Cellular Mechanics and Interactions
- Clostridium difficile and Clostridium perfringens research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Renal and related cancers
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Digestive system and related health
- Signaling Pathways in Disease
The University of Texas MD Anderson Cancer Center
2019-2024
The University of Texas Health Science Center at Houston
2021-2023
Children's Hospital of Philadelphia
2017-2020
University of Pennsylvania
2018-2020
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with an immunosuppressive microenvironment that is resistant to most therapies. IL17 involved in pancreatic tumorigenesis, but its role invasive PDAC undetermined. We hypothesized triggers and sustains immunosuppression. inhibited IL17/IL17RA signaling using pharmacological genetic strategies alongside mass cytometry multiplex immunofluorescence techniques. uncovered recruits neutrophils, neutrophil extracellular traps...
T cell activation by dendritic cells (DCs) involves forces exerted the actin cytoskeleton, which are opposed cortical cytoskeleton of interacting antigen-presenting cell. During an immune response, DCs undergo a maturation process that optimizes their ability to efficiently prime naïve cells. Using atomic force microscopy, we find during maturation, DC stiffness increases via polymerization. stimulatory hydrogels and expressing mutant cytoskeletal proteins, increasing lowers agonist dose...
Tumor-resident microbes (TRM) are an integral component of the tumor microenvironment (TME). TRM can influence growth, distant dissemination, and response to therapies by interfering with molecular pathways in cells as well other components TME. Novel technologies improving identification visualization cell type-specific The mechanisms that mediate role at primary tumors metastatic sites being elucidated. This knowledge is providing novel perspectives for targeting or using microbial...
Full T cell activation requires coordination of signals from multiple receptor-ligand pairs that interact in parallel at a specialized cell-cell contact site termed the immunological synapse (IS). Signaling IS is intimately associated with actin dynamics; receptor (TCR) engagement induces centripetal flow network, which turn enhances function ligand-bound integrins by promoting conformational change. Here, we have investigated effects integrin on flow, and signaling events downstream TCR. We...
Abstract The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process tumorigenesis would aid in establishing targets for effective prevention therapy. Here, we interrogated differential molecular mechanisms dependent on cell origin subtype promote PDAC initiation established tumors. Transcriptomic analysis cell-of-origin–dependent epithelial gene signatures...
Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is an aggressive disease with a poor prognosis.1 Surgery the only potential curative treatment, but it possible in patients early-stage disease, and most present non-resectable disease.1 Even who undergo resection, recurrence rate very high due to early systemic dissemination.2 Combinatorial chemotherapy remains standard of care for advanced responses are heterogeneous, its toxicity limits treatment duration.3–5 Results...
ABSTRACT T cell activation by dendritic cells (DCs) involves forces exerted the actin cytoskeleton, which are opposed cortical cytoskeleton of interacting APC. During an immune response, DCs undergo a maturation process that optimizes their ability to efficiently prime naïve cells. Using atomic force microscopy, we find during maturation, DC stiffness increases via polymerization. stimulatory hydrogels and expressing mutant cytoskeletal proteins, increasing lowers agonist dose needed for...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related deaths by 2030, and currently has a 5-year survival rate roughly 10%. With long-term rates in patients being exceedingly low, understanding what factors delineate imperative. When comparing spontaneous transgenic mouse models pancreatic cancer housed geographically distinct vivaria, regardless common lineage, we observed drastically different phenotype states respective...
Abstract Pancreatic ductal adenocarcinoma (PDAC) has become the third leading cause of cancer-related death in United States with high resistance to therapies, presentation at late stages and aggressive biology. Immunotherapy revolutionized cancer therapy by offering survival benefit many solid malignancies, however, it is still not effective pancreatic cancer. Host factors are crucial modulators responses immunotherapy. The roles gut microbiome modulating immune system determining outcomes...
Abstract Immune checkpoint inhibitors (ICI) have notably improved overall survival rates across various cancers, particularly in cases of mismatch repair deficient cancer (MMRd). However, numerous factors influence patient response following ICI treatment. Beyond genetic factors, mutations, and levels immune cell infiltration, several studies highlight the correlation between gut microbiome treatment rates. Furthermore, specific bacterial compositions been observed to shift during...
Abstract Pancreatic ductal adenocarcinoma (PDAC), the most aggressive type of pancreatic cancer, is predicted to become second leading cause cancer related deaths by 2030. Interleukin 17 (IL-17) signaling can promote tumor growth. In IL-17 in cells capable triggering formation neutrophil extracellular traps (NETs) which detrimental anti-tumor effect immunotherapy. has been shown have critical roles maintaining gut homeostasis. Intestinal epithelial directly interact with microbiome and are...
Abstract Preclinical studies suggest that aerobic exercise influences the tumor microenvironment by normalizing vasculature and reducing immunosuppression in Pancreatic Ductal Adenocarcinoma (PDAC). Gut microbes can influence PDAC progression modulating metabolic immune pathways. However, a knowledge gap remains regarding role of gut microbiome anti-tumor effects exercise. We hypothesized exercise-induced effect is regulated microbiome. compared treadmill running on growth orthotopic C57BL/6...
<p>Supplementary Figures S1-9</p>
The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding initial triggers of immunosuppression during the process tumorigenesis would aid in establishing novel targets for effective prevention therapy. Here, we interrogate differential molecular mechanisms dependent on cell origin pathology subtype determine PDAC initiation established tumors. Transcriptomic analysis dependent-epithelial gene signatures...
ABSTRACT The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding initial triggers of immunosuppression during the process tumorigenesis would aid in establishing novel targets for effective prevention therapy. Here, we interrogate differential molecular mechanisms dependent on cell origin pathology subtype determine PDAC initiation established tumors. Transcriptomic analysis dependent-epithelial gene...
Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role pancreatic development and homeostasis, we conditionally deleted from murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due malabsorption associated with...
Abstract Introduction: The all stages combined five-year survival rate for pancreatic adenocarcinoma (PDA) is 11%; however, the localized PDA 42%. These statistics highlight importance of early prevention strategies to prevent disease progression and metastatic dissemination. Through NCI PREVENT program, this research program explores immunoprevention by targeting CD73, a gatekeeper ectoenzyme responsible production extracellular adenosine. We have recently shown aggressive subtypes...
<p>Supplementary Figures S1-9</p>
<p>Supplementary Figures S1-9</p>