A5103188976- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Dermatology and Skin Diseases
- vaccines and immunoinformatics approaches
- Telomeres, Telomerase, and Senescence
- Immune cells in cancer
- SARS-CoV-2 and COVID-19 Research
- Genomics and Chromatin Dynamics
- Vector-borne infectious diseases
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Acute Myeloid Leukemia Research
- IL-33, ST2, and ILC Pathways
- Pulmonary Hypertension Research and Treatments
- COVID-19 Clinical Research Studies
- Chronic Myeloid Leukemia Treatments
- RNA Interference and Gene Delivery
- Pharmacological Effects of Natural Compounds
- Viral Infections and Vectors
National Institute on Aging
2022-2025
National Institutes of Health
2006-2024
Institute on Aging
2022-2024
Johns Hopkins University
2012-2023
Johns Hopkins Medicine
2006-2023
Institut thématique Génétique, génomique et bioinformatique
2022
Genomics (United Kingdom)
2022
Sidney Kimmel Comprehensive Cancer Center
2015-2017
University of Maryland, Baltimore
2007-2009
Abstract Purpose: Blocking the immunosuppressive PD-1/PD-L1 pathway has antitumor activity in multiple cancer types, and PD-L1 expression on tumor cells infiltrating myeloid correlates with likelihood of response. We previously found that IFNG (interferon-gamma) was overexpressed by tumor-infiltrating lymphocytes PD-L1+ versus PD-L1(−) melanomas, creating adaptive immune resistance promoting display. This study undertaken to identify additional factors melanoma microenvironment coordinately...
The functions of key oncogenic transcription factors independent context have not been fully delineated despite our richer understanding the genetic alterations in human cancers. MYC oncogene, which produces Myc factor, is frequently altered cancer and a major regulatory hub for many In this regard, we sought to unravel primordial signature function by using high-throughput genomic approaches identify cell-type core target gene signature. Using model B lymphoma cells bearing inducible MYC,...
Pretreatment tumor PD-L1 expression has been shown to correlate with response anti-PD-1/PD-L1 therapies. Yet, most patients PD-L1(+) tumors do not respond treatment. The current study was undertaken investigate mechanisms underlying the failure of PD-1-targeted therapies in advanced renal cell carcinoma (RCC) whose express PD-L1. Formalin-fixed, paraffin-embedded pretreatment biopsies expressing were derived from 13 RCC patients. RNA isolated regions and subjected whole genome microarray...
Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing toward distinct subpopulations. The subpopulations reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis with unsupervised clustering, we found 11 macrophage clusters male mouse SKM enriched gene expression programs linked to reparative, proinflammatory, phagocytic, proliferative,...
Abstract HuR is a regulator of mRNA turnover or translation inflammatory genes through binding to adenylate-uridylate–rich elements and related motifs present in the 3′untranslated region (UTR) mRNAs. We postulate that critically regulates epithelial response by associating with multiple ARE-bearing, functionally transcripts. aimed identify targets human airway cell line BEAS-2B challenged TNF-α plus IFN-γ, strong stimulus for responses. Ribonucleoprotein complexes from resting...
Abstract BACKGROUND Despite advances in screening and local therapy, prostate cancer remains the second most common cause of related death among American men, with those having high grade disease being at highest risk for mortality. Here we identify genes cellular pathways that distinguish from low pathologically localized cancer. METHODS Cancer cells (Gleason 3 + = 6) or (4 4 8) tumors men were isolated by laser capture micro‐dissection. Expression profiling was conducted across 18,344...
To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient widely metastatic melanoma who had heterogeneous response.
Senescent vascular smooth muscle cells (VSMCs) accumulate in the vasculature with age and tissue damage secrete factors that promote atherosclerotic plaque vulnerability disease. Here, we report increased levels activity of dipeptidyl peptidase 4 (DPP4), a serine protease, senescent VSMCs. Analysis conditioned media from VSMCs revealed unique senescence-associated secretory phenotype (SASP) signature comprising many complement coagulation factors; silencing or inhibiting DPP4 reduced these...
Gene expression profiling of peripheral blood mononuclear cells (PBMCs) is a powerful tool for the identification surrogate markers involved in disease processes. The hypothesis tested this study was that chronic exposure PBMCs to hypertensive environment remodeled pulmonary vessels would be reflected by specific transcriptional changes these cells.The transcript profiles from 30 idiopathic arterial hypertension patients (IPAH), 19 with systemic sclerosis without (SSc), 42...
Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions aim at selectively eliminating senescent cells. In this study, drug library screen uncovered TrkB (NTRK2) inhibitors capable of triggering apoptosis several senescent, but not proliferating, human Senescent...
ABSTRACT The study of biomarkers in biofluids and tissues expanded our understanding the biological processes that drive physiological functional manifestations aging. However, most these studies were limited to examining one compartment, an approach fails recognize aging pervasively affects whole body. simultaneous modeling hundreds metabolites proteins across multiple compartments may provide a more detailed picture healthy point differences between chronological Herein, we report...
Three-dimensional genome organization orchestrates recombination and transcription of immunoglobulin heavy chain (Igh) genes. The structure wild-type (WT) alleles includes a prominent architectural stripe that extends from cluster CTCF binding elements at the 3' end locus (3'CBE), suggesting interactions this with sequences throughout 2 Mb Igh TAD. Here we elucidate interplay between regulatory located in 3'Igh domain (260 kb) impact stripe. CTCF-lacking intronic enhancer, Eµ, promotes...
Senescent cells release a variety of cytokines, proteases, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Sustained SASP contributes to pattern chronic inflammation associated with aging implicated in many age-related diseases. Here, we investigated expression function immunomodulatory cytokine BAFF (B-cell activating factor; encoded by TNFSF13B gene), protein, multiple senescence models. We first characterized production across different...
Abstract The posttranscriptional mechanisms whereby RNA-binding proteins (RBPs) regulate T cell differentiation remain unclear. RBPs can coordinately the expression of functionally related genes via binding to shared regulatory sequences, such as adenylate-uridylate–rich elements (AREs) present in 3′ untranslated region (UTR) mRNA. RBP HuR posttranscriptionally regulates IL-4, IL-13, and other Th2 cell-restricted transcripts. We hypothesized that ARE-bearing GATA-3 gene, a critical regulator...
Ulcerative colitis (UC) is a chronic, relapsing and debilitating idiopathic inflammation, with variable complex pathophysiologies. Our objective was to elucidate patterns of gene expression underlying the progression UC disease. Single endoscopic pinch FFPE biopsies (n = 41) were sampled at both active inactive stages same site in individual patients compared each other non-inflammatory bowel disease healthy controls. Gene results validated by quantitative reverse transcriptase-PCR...
Abstract The resolution of SARS-CoV-2 replication hinges on cell-mediated immunity, wherein CD8 + T cells play a vital role. Nonetheless, the characterization specificity and TCR composition targeting non-spike protein before after infection remains incomplete. Here, we analyzed recognizing six epitopes from nucleocapsid (N) found that slightly increased frequencies N-recognizing but significantly enhanced activation-induced proliferation compared to uninfected donors. N-specific their...
Although epigenetic mechanisms are important risk factors for allergic disease, few studies have evaluated DNA methylation differences associated with atopic dermatitis (AD), and none has focused on AD eczema herpeticum (ADEH+). We will determine how varies in individuals with/without EH traits. modeled genome-wide whole blood cells from 90 ADEH+, 83 ADEH−, 84 non-atopic, healthy control subjects, replicating 36 53 55 non-atopic subjects. adjusted cell-type composition our models used...
Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics facilitate implantation process, has been a standard practice. The effect of different types support using steroid hormones relation miRNA profiles during peri-implantation period not seen described. This study was designed evaluate expression miRNAs following...
Abstract DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of methylation, is typically enriched at enhancers and gene bodies transcriptionally active tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role aging remains unknown. Here, using mouse liver cerebellum as model organs, we show that accumulates associated with function restricts magnitude expression changes age. Mechanistically, decreases binding...