A5026802721- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Immune cells in cancer
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- Lung Cancer Treatments and Mutations
- Escherichia coli research studies
- vaccines and immunoinformatics approaches
- Peptidase Inhibition and Analysis
- Virus-based gene therapy research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Cells and Metastasis
- interferon and immune responses
- Colorectal Cancer Treatments and Studies
- Viral gastroenteritis research and epidemiology
- Chronic Lymphocytic Leukemia Research
- Phagocytosis and Immune Regulation
- Hippo pathway signaling and YAP/TAZ
- Fibroblast Growth Factor Research
- Biochemical and Molecular Research
- Extracellular vesicles in disease
- Inflammasome and immune disorders
The University of Texas MD Anderson Cancer Center
2010-2025
Anderson University - South Carolina
2024
University of Houston
2021
Molecular Oncology (United States)
2017-2018
Baylor College of Medicine
2016
Houston Methodist
2011-2015
Methodist Hospital
2012
Methodist Hospital
2011
Osaka City University
2005-2007
Abstract Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell (NSCLC) subtypes with oncogenic alterations EGFR, ALK and KRAS. The success limited by drug-tolerant persister cells (DTPs) which withstand adapt to treatment comprise residual disease state that typical during clinical therapies. Here, we integrate studies patient-derived immunocompetent...
Human tumor xenograft models do not replicate the human immune system and microenvironment. We developed an improved humanized mouse model, derived from fresh cord blood CD34+ stem cells (CD34+ HSC), combined it with lung cancer cell line-derived xenografts or patient-derived (Hu-PDX). Fresh HSCs could reconstitute detectable mature leukocytes (hCD45+) in mice at four weeks without onset of graft-versus-host disease (GVHD). Repopulated T cells, B natural killer (NK) dendritic (DC),...
Abstract Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established landscapes 536 patient-derived xenograft (PDX) models across 25 types, together mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared human tumors, PDXs typically higher purity fit dynamic driver events molecular properties via multiple...
Functionalization of nanoparticles with cationic moieties, such as polyethyleneimine (PEI), enhances binding to the cell membrane; however, it also disrupts integrity cell's plasma and vesicular membranes, leading death. Primary fibroblasts were found display high surface affinity for iron oxide greater sensitivity than their immortalized counterparts. Treatment cells in presence incremental increases serum led a corresponding linear decrease The potential decreased linearly increased this...
Expression of NPRL2/TUSC4 , a tumor-suppressor gene, is reduced in many cancers including NSCLC. Restoration NPRL2 induces DNA damage, apoptosis, and cell-cycle arrest. We investigated antitumor immune responses aPD1 R / KRAS/STK11 mt NSCLC humanized-mice. Humanized-mice were generated by transplanting fresh human cord blood-derived CD34 stem cells into sub-lethally irradiated NSG mice. Lung-metastases developed from /aPD1 A549 treated with w/wo pembrolizumab. -treatment lung metastases...
Abstract Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy dismal prognosis. Here, we corroborated findings by using immune-humanized, syngeneic, genetically engineered mouse models cancer harboring deficiency. Specifically, with loss showed decreased response anti-PD1...
Sotorasib (AMG510) and adagrasib (MRTX849) have shown significant efficacy in KRASG12C mutant NSCLC, but acquired resistance occurs within 6-12 months. While some arises from new mutations, over half of the resistant cases lack identifiable genomic alterations. We hypothesize that is driven by signaling network rewiring, creating therapeutic vulnerabilities. To investigate (AR) mechanisms, multiple AR models, including cell lines (H23AR & H358AR), PDXs (TC303AR TC314AR), CDXs (H358AR...
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). delivered systemically nanovesicles has mediated regression clinical trials. Because role regulating immune cells, we assessed efficacy on antitumor responses alone and combination with anti-PD-1 two Kras-mutant syngeneic mouse cancer models. significantly reduced growth prolonged survival compared anti-PD-1. When combined, this...
Porous silicon microparticles presenting pathogen-associated molecular patterns mimic pathogens, enhancing internalization of the and activation antigen dendritic cells. We demonstrate abundant uptake bound by TLR-4 ligands LPS MPL murine bone marrow-derived cells (BMDC). Labeled induce concentration-dependent production IL-1β, with inhibition caspase inhibitor Z-VAD-FMK supporting NLRP3-dependent inflammasome. Inoculation BALB/c mice ligand-bound induces a significant increase in...
Abstract KRAS/LKB1 (STK11) NSCLC metastatic tumors are intrinsically resistant to anti-PD-1 or PD-L1 immunotherapy. In this study, we use a humanized mouse model show that while carboplatin plus pembrolizumab reduce tumor growth moderately and transiently, the addition of suppressor gene TUSC2, delivered systemically in nanovesicles, combination, eradicates majority animals. Immunoprofiling microenvironment shows TUSC2 mediates: (a) significant infiltration reconstituted human functional...
We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access National Cancer Institute-funded PDXNet consortium resources, facilitate collaboration among researchers and make these data easily available for research. The includes sections analysis results, metrics activities, processing protocols training materials data. Currently, contains model information resources from 334 new models across 33 cancer types. Tissue samples of were deposited in NCI's...
Dendritic cells (DC) process and present antigens to T lymphocytes, inducing potent immune responses when encountered in association with activating signals, such as pathogen-associated molecular patterns. Using the 4T1 murine model of breast cancer, cationic liposomes containing monophosphoryl lipid A (MPL) interleukin (IL)-12 were administered by intratumoral injection. Combination multivalent presentation Toll-like receptor-4 ligand MPL cytotoxic 1,2-dioleoyl-3-trmethylammonium-propane...
Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi contrast free MPL, resulted the induction local inflammation, reflected recruitment neutrophils, eosinophils proinflammatory monocytes, depletion resident macrophages mast cells at site. Injection microparticle-bound MPL enhanced secretion T helper 1 associated cytokines IFN-γ...
BackgroundEnteropathogens cannot be identified in 40% to 50% of subjects with travelers' diarrhea (TD).
Expression of the TUSC2 tumor-suppressor gene in TUSC2-deficient NSCLC cells decreased PD-L1 expression and inhibited mTOR activity. Overexpressing or treatment with rapamycin resulted similar inhibition expression. Both p70 SK6 phosphorylation, suggesting that share same target. Microarray mRNA analysis using TUSC2-inducible H1299 showed genes negatively regulate pathway were significantly upregulated by compared control. The presence IFN-γ increased lung cancer cell lines, but...
Escherichia coli that adhere sparsely to human epithelial (HEp-2) cells are known as diffusely adherent E. coli(DAEC) and considered potentially diarrheagenic. The role of the afimbrial adhesive sheath (Afa)-identified originally a uropathogenic factor-in diffuse adhesion is now understood. However, DAEC in diarrheal disease remains controversial. Recently, ability induce interleukin-8 (IL-8) secretion from intestinal has been suggested one properties enterovirulent bacteria. In this study,...
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer patients; however, antigenic targets these reinvigorated T cells remain poorly defined. Lung tumors contain tumor-associated macrophages (TAM) and neutrophils, which release serine proteases neutrophil elastase (NE) proteinase 3 (P3) into tumor microenvironment. NE P3 shape antitumor adaptive response breast melanoma. In this report, we demonstrate that cross-presented antigen PR1,...
Herein, we present a novel imaging platform to study the biological effects of non-invasive radiofrequency (RF) electric field cancer hyperthermia. This system allows for real-time in vivo intravital microscopy (IVM) radiofrequency-induced alterations such as changes vessel structure and drug perfusion. Our results indicate that IVM is able handle exposure high-power electric-fields without inducing significant hardware damage or artifacts. Furthermore, short durations low-power (< 200 W)...
Escherichia coli that sparsely adhere to human epithelial cells are known as diffusely adherent E. (DAEC), and the role of Afa/Dr family adhesins is now understood. Strains do not possess Afa/Dr, however, comprise another group DAEC, which pathogenicity remains unknown. The ability induce interleukin-8 (IL-8) secretion from intestinal might be a feature enterovirulent bacteria. We previously found some DAEC strains IL-8 by stimulating with flagella. present study examines whether non-Afa/Dr...
The role of diffusely adherent Escherichia coli (DAEC) in diarrheal disease has been controversial. However, DAEC strains were recently implicated developing countries. To clarify whether are prevalent among sporadic cases illness Osaka City, Japan, E. isolated between July 1997 and March 2000 during diarrheagenic (DEC) investigation retrospectively examined. recognized 41 (4.4%) 924 patients formed the biggest subgroup DEC. Previously, we reported that some caused epithelial cells to...
Tracking vaccine components from the site of injection to their destination in lymphatic tissue, and simultaneously monitoring immune effects, sheds light on influence particle cell trafficking therapeutic efficacy. In this study, we create a hybrid platform comprised porous silicon (pSi) superparamagnetic iron oxide nanoparticles (SPIONs). The impact nanoparticle size mode presentation magnetic resonance contrast enhancement are examined. SPION-enhanced relaxivity increased as core diameter...
Anti-PD-1 and anti-PD-L1 immunotherapy has provided a new therapeutic opportunity for treatment of advanced-stage non-small cell lung cancer (NSCLC). However, overall objective response rates are approximately 15%–25% in all NSCLC patients who receive anti-PD therapy. Therefore, strategies to overcome primary resistance urgently needed. We hypothesized that the barrier success therapy most can be by stimulating lymphocyte infiltration at sites through locoregional virotherapy. To this end,...
Abstract Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell (NSCLC) subtypes with oncogenic alterations EGFR, ALK and KRAS. The success limited by drug-tolerant cells which withstand adapt to treatment comprise residual disease state that typical during clinical therapies. Here, we integrate studies patient-derived immunocompetent models specimens...
Because patient-derived xenografts (PDXs) are grown in immunodeficient mouse strains, PDXs regarded as lacking an immune microenvironment. However, whether patients' cells co-exist remains uncharacterized. We cultured small pieces of lung PDX tissue media containing human interleukin-2 and characterized the proliferated lymphocytes by flow cytometric assays with antibodies specific for cell surface markers. Presence was also determined immunohistochemical staining. Human tumor-infiltrating...