A5002107110- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
- Liver Disease Diagnosis and Treatment
- interferon and immune responses
- Tuberculosis Research and Epidemiology
- Folate and B Vitamins Research
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Genomics and Rare Diseases
- Mycobacterium research and diagnosis
- Viral Infections and Immunology Research
- Eosinophilic Esophagitis
- Esophageal and GI Pathology
- Hepatitis Viruses Studies and Epidemiology
- Lipid metabolism and biosynthesis
- Genetics and Neurodevelopmental Disorders
- Diabetes and associated disorders
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- Cardiomyopathy and Myosin Studies
- Whipple's Disease and Interleukins
Bilkent University
2021-2025
Rockefeller University
2016-2024
National Nanotechnology Research Center
2024
Sağlık Bilimleri Üniversitesi
2023
Izmir Kâtip Çelebi University
2023
Izmir University
2023
Erciyes University
2022
The University of Texas Southwestern Medical Center
2010-2020
Sabancı Üniversitesi
2012
Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe at 2 yr. She is homozygous for loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced IFN-α2b the patient's much narrower than that control cells; however, induction subset transcripts remains...
Vaccination against measles, mumps, and rubella (MMR) yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines be caused inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy Iran severe measles disease at 1 yr 14-yr-old girl Brazil viscerotropic 12 yr. The Iranian...
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 or RNASEL five unrelated with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing generate 2′-5′-linked oligoadenylates (2-5A) activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines primary myeloid cells OAS1, OAS2, RNase produce excessive amounts cytokines upon dsRNA acute...
We hypothesize that low-level efflux pump expression is the first step in development of high-level drug resistance mycobacteria. performed 28-day azithromycin dose-effect and dose-scheduling studies our hollow-fiber model disseminated Mycobacterium avium-M. intracellulare complex. Both microbial kill emergence were most closely linked to within-macrophage area under concentration-time curve (AUC)/MIC ratio. Quantitative PCR revealed subtherapeutic exposures over 3 days led a 56-fold...
Juvenile-onset recurrent respiratory papillomatosis (JRRP) is a rare and debilitating childhood disease that presents with growth of papillomas in the upper airway. Two common human papillomaviruses (HPVs), HPV-6 -11, are implicated most cases, but it still not understood why only small proportion children develop JRRP following exposure to these viruses. We report 2 siblings syndromic form associated mild dermatologic abnormalities. Whole-exome sequencing patients revealed private...
Fulminant viral hepatitis (FVH) is a devastating and unexplained condition that strikes otherwise healthy individuals during primary infection with common liver-tropic viruses. We report child who died of FVH upon A virus (HAV) at age 11 yr was homozygous for private 40-nucleotide deletion in IL18BP, which encodes the IL-18 binding protein (IL-18BP). This mutation loss-of-function, unlike variants found state public databases. show human IL-18BP are both secreted mostly by hepatocytes...
Abstract T cell activation involves a cascade of TCR-mediated signals that are regulated by three distinct intracellular signaling motifs located within the cytoplasmic tails CD3 chains. Whereas all subunits possess at least one ITAM, ε subunit also contains proline-rich sequence and basic-rich stretch (BRS). The BRS complexes selected phosphoinositides, interactions required for normal surface expression TCR. domain ζ several clusters arginine lysine residues. In this study, we report these...
Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained
Cytomegalovirus (CMV) can cause severe disease in children and adults with a variety of inherited or acquired T-cell immunodeficiencies, who are prone to multiple infections. It also rarely otherwise healthy persons. The pathogenesis idiopathic CMV is unknown. Inbred mice that lack the gene encoding nitric oxide synthase 2 (Nos2) susceptible related murine infection.We studied previously 51-year-old man from Iran after acute infection had an onset progressive led his death 29 months later....
Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes PNPLA3 148I and 148M variants engrafted the livers of broadly immunodeficient chimeric mice respond hypercaloric diets. As early as four weeks, developed dyslipidemia, impaired...
Background Physiological stress evokes rapid changes in both the innate and adaptive immune response. Immature αβ T cells developing thymus are particularly sensitive to stress, with infections and/or exposure lipopolysaccharide or glucocorticoids eliciting a apoptotic program. MicroRNAs class of small, non-coding RNAs that regulate global gene expression by targeting diverse mRNAs for degradation. We hypothesized subset thymically encoded microRNAs would be responsive modulate thymopoiesis....
We studied a child with severe viral, bacterial, fungal, and parasitic diseases, who was homozygous for loss-of-function mutation of REL, encoding c-Rel, which is selectively expressed in lymphoid myeloid cells. The patient had low frequencies NK, effector memory cells reexpressing CD45RA (Temra) CD8+ T cells, CD4+ including Th1 Th1*, Tregs, B whereas the counts proportions other leukocyte subsets were normal. Functional deficits included abolition IL-12 IL-23 production by conventional DC1s...
Abstract Fulminant viral hepatitis (FVH) caused by A virus (HAV) is a life-threatening disease that typically strikes otherwise healthy individuals. The only known genetic etiology of FVH inherited IL-18BP deficiency, which unleashes IL-18-dependent lymphocyte cytotoxicity and IFN-γ production. We studied two siblings who died from combination early-onset inflammatory bowel (EOIBD) due to HAV. sibling tested was homozygous for the W100G variant IL10RB previously described in an unrelated...
Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+)CD8(+) thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs) the thymus upon systemic induced by lipopolysaccharide (LPS) or synthetic glucocorticoid, dexamethasone (Dex). MiRs are short, non-coding RNAs that play critical roles immune system targeting diverse mRNAs, suggesting their modulation response...
IL37 plays important roles in the regulation of innate immunity and its oligomeric status is critical to these roles. In monomeric state, can effectively inhibit inflammatory response IL18 by binding IL18Rα, a capacity lost dimeric form, underlining pivotal role anti-inflammatory action. Until now, two dimer structures have been deposited PDB, reflecting substantial difference their interfaces. Given this discrepancy, we analyzed PDB (PDB: 6ncu, 5hn1) along with AF2-multimer prediction...
Genome-wide approaches, such as whole-exome sequencing (WES), are widely used to decipher the genetic mechanisms underlying inter-individual variability in disease susceptibility. We aimed dissect inborn monogenic determinants of idiopathic liver injury otherwise healthy children. thus performed WES for 20 patients presented with paediatric-onset recurrent elevated transaminases (rELT) or acute failure (ALF) unknown aetiology. A stringent variant screening was undertaken on a...