Derya Unutmaz

Mucosal-associated invariant T (MAIT) cells play diverse roles in cancer, infectious diseases, and immunotherapy. This review explores their intricate involvement in cancer, from early detection to their dual functions in promoting inflammation and mediating anti-tumor responses. Within the solid tumor microenvironment (TME), MAIT cells can acquire an 'exhausted' state and secrete tumor-promoting cytokines. On the other hand, MAIT cells are highly cytotoxic, and there is evidence that they may have an anti-tumor immune response...

Aryl hydrocarbon receptor (AhR) is a transcription factor that regulates gene expression upon ligand activation, enabling microbiota-dependent induction, training, and function of the host immune system. A spectrum of metabolites, encompassing indole and tryptophan derivatives, have been recognized as activators. This work introduces an integrated, mass spectrometry-centric workflow that employs a bioassay-guided, fractionation-based methodology for the identification of AhR activators derived from human bacterial isolates...

OBJECTIVE: Chronic rhinosinusitis (CRS) impacts an estimated 5% to 15% of people worldwide, incurring significant economic healthcare burden. There is a urgent need for the discovery of predictive biomarkers to improve treatment strategies and outcomes for CRS patients. STUDY DESIGN: Cohort study of CRS patients and healthy controls using blood samples. SETTING: Out-patient clinics. METHODS: Whole blood samples were collected for flow cytometric analysis...

INTRODUCTION: Cognitive impairment is experienced by people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of COVID-19 (PASC). Patients report difficulty remembering, concentrating, and making decisions. Our objective was to determine whether orthostatic hemodynamic changes were causally linked to cognitive impairment in these diseases. METHODS: This prospective, observational cohort study enrolled PASC, ME/CFS, and healthy controls...

BACKGROUND & AIMS: Glycoprotein A repetitions predominant (GARP) is a membrane protein that functions as a latent TGF-β docking molecule. While the immune regulatory properties of GARP on blood cells have been studied, the function of GARP on tissue stromal cells remains unclear. Here, we investigate the role of GARP expressed on hepatic stellate cells (HSCs) in the development of liver fibrosis. METHODS: The function of GARP on HSCs was explored in toxin-induced and metabolic liver fibrosis models, using conditional GARP-deficient mice or a newly generated inducible system for HSC-specific gene ablation...

The genome is pervasively transcribed to produce a vast array of non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides and are best known for their ability to regulate gene expression. Enhancer RNAs (eRNAs) are subclass of lncRNAs that are synthesized from enhancer regions and have also been shown to coordinate gene expression. The biological function and significance of most lncRNAs and eRNAs remain to be determined. Epithelial to mesenchymal transition (EMT) is a ubiquitous cellular process that occurs during cellular migration, homeostasis, fibrosis, and cancer-cell metastasis...

BACKGROUND: Long COVID describes a condition with symptoms that linger for months to years following acute COVID-19. Many of these Long COVID symptoms are like those experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). OBJECTIVE: We wanted to determine if people with Long COVID experienced post-exertional malaise (PEM), the hallmark symptom of ME/CFS, and if so, how it compared to PEM experienced by patients with ME/CFS. METHODS: A questionnaire that asked about the domains of PEM including triggers, experience, recovery, and prevention was administered to 80 people seeking care for Long COVID at Bateman Horne Center...

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disorder manifesting as severe fatigue and post-exertional malaise. The etiology of ME/CFS remains elusive. Here, we present a deep metagenomic analysis of stool combined with plasma metabolomics and clinical phenotyping of two ME/CFS cohorts with short-term (<4 years, n = 75) or long-term disease (>10 years, n = 79) compared with healthy controls (n = 79). First, we describe microbial and metabolomic dysbiosis in ME/CFS patients...

Objectives: Despite advances in antibody treatments and vaccines, COVID-19 caused by SARS-CoV-2 infection remains a major health problem resulting in excessive morbidity and mortality and the emergence of new variants has reduced the effectiveness of current vaccines. Methods: Here, as a proof-of-concept, we engineered primary CD8 T cells to express SARS-CoV-2 Spike protein-specific CARs, using the extracellular region of ACE2 and demonstrated their highly specific and potent cytotoxicity towards Spike-expressing target cells...

Aims: Studies have linked severe hyperoxia, or prolonged exposure to very high oxygen levels, with worse clinical outcomes. This study investigated the role of epidermal growth factor receptor (EGFR) in hyperoxia-induced lung injury at very high oxygen levels (>95%). Results: Effects of severe hyperoxia (100% oxygen) were studied in mice with genetically inhibited EGFR and wild-type littermates. Despite the established role of EGFR in lung repair, EGFR inhibition led to improved survival and reduced acute lung injury, which prompted an investigation into this protective mechanism...

Engineering immune cells with chimeric Ag receptors (CARs) is a promising technology in cancer immunotherapy. Besides classical cytotoxic CD8+ T cells, innate cell types such as NK cells have also been used to generate CAR-T or CAR-NK cells. In this study, we devised an approach to program a nonclassical cytotoxic T cell subset called mucosal-associated invariant T (MAIT) cells into effective CAR-T cells against B cell lymphoma and breast cancer cells. Accordingly, we expressed anti-CD19 and anti-Her2 CARs in activated primary human MAIT cells and CD8+ T cells, expanded them in vitro, and compared their cytotoxicity against tumor cell targets...

Immunotherapy has revolutionized cancer treatment with the advent of advanced cell engineering techniques aimed at targeted therapy with reduced systemic toxicity. However, understanding the underlying immune-cancer interactions require development of advanced three-dimensional (3D) models of human tissues. In this study, we fabricated 3D tumor models with increasing complexity to study the cytotoxic responses of CD8+ T cells, genetically engineered to express mucosal-associated invariant T (MAIT) cell receptors, towards MDA-MB-231 breast cancer cells...

The determinants of severe COVID-19 in healthy adults are poorly understood, which limits the opportunity for early intervention. We present a multiomic analysis using machine learning to characterize the genomic basis of COVID-19 severity. We use single-cell multiome profiling of human lungs to link genetic signals to cell-type-specific functions. We discover >1,000 risk genes across 19 cell types, which account for 77% of the SNP-based heritability for severe disease. Genetic risk is particularly focused within natural killer (NK) cells and T cells, placing the dysfunction of these cells upstream of severe disease...

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Aging has emerged as the greatest and most prevalent risk factor for the development of severe COVID-19 infection and death following exposure to the SARS-CoV-2 virus. The presence of multiple co-existing chronic diseases and conditions of aging further enhances this risk. Biological aging not only enhances the risk of chronic diseases, but the presence of such conditions further accelerates varied biological processes or "hallmarks" implicated in aging. Given growing evidence that it is possible to slow the rate of many biological aging processes using pharmacological compounds has led to the proposal that such geroscience-guided interventions may help enhance immune resilience and improve outcomes in the face of SARS-CoV-2 infection...

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial. METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines...

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial. METHODS: W e performed a prospective longitudinal cohort study evaluating SARS-CoV-2 Spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines...

Over the last few decades, the world has witnessed multiple viral pandemics, the current severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic being the worst and most devastating one, claiming millions of lives worldwide. Physicians, scientists, and engineers worldwide have joined hands in dealing with the current situation at an impressive speed and efficiency. One of the major reasons for the delay in response is our limited understanding of the mechanism of action and individual effects of the virus on different tissues and organs...

BACKGROUND: PD-1 marks exhausted T cells, with weak effector functions. Adults living with HIV have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV. METHODS: We enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells, their coexpression with immune checkpoints (IC) 2B4, CD160 and TIM3, correlates with immune activation and HIV disease progression and HIV-specific and non-specific proliferative responses...

Metastatic breast cancer is one of the deadliest forms of malignancy, primarily driven by its characteristic micro-environment comprising cancer cells interacting with stromal components. These interactions induce genetic and metabolic alterations creating a conducive environment for tumor growth. In this study, a physiologically relevant 3D vascularized breast cancer micro-environment is developed comprising of metastatic MDA-MB-231 cells and human umbilical vein endothelial cells loaded in human dermal fibroblasts laden fibrin, representing the tumor stroma...