ORCID Profile
0000-0001-7457-9164
Current Organisation
University of South Australia
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Publisher: Wiley
Date: 28-02-2020
DOI: 10.1111/FAF.12449
Publisher: Springer Science and Business Media LLC
Date: 13-12-2019
DOI: 10.1038/S41467-019-13082-9
Abstract: Increased levels and non-telomeric roles have been reported for shelterin proteins, including RAP1 in cancers. Herein using Rap1 null mice, we provide the genetic evidence that mammalian Rap1 plays a major role in hematopoietic stem cell survival, oncogenesis and response to chemotherapy. Strikingly, this function of RAP1 is independent of its association with the telomere or with its known partner TRF2. We show that RAP1 interacts with many members of the DNA damage response (DDR) pathway. RAP1 depleted cells show reduced interaction between XRCC4/DNA Ligase IV and DNA-PK, and are impaired in DNA Ligase IV recruitment to damaged chromatin for efficient repair. Consistent with its role in DNA damage repair, RAP1 loss decreases double-strand break repair via NHEJ in vivo, and consequently reduces B cell class switch recombination. Finally, we discover that RAP1 levels are predictive of the success of chemotherapy in breast and colon cancer.
Publisher: Proceedings of the National Academy of Sciences
Date: 26-07-2019
Abstract: In the present study, we identify and describe an important cross-talk between leptin signaling and macrophage functions in the context of Salmonella Typhimurium infection. Genetic ablation of leptin receptor or pharmacological antagonization of leptin augmented lysosomal functions in macrophages, reduced S. Typhimurium burden, and diminished inflammation both in vitro and in vivo. Leptin signaling activates mTORC2/Akt pathway through the down-regulation of Phlpp1 phosphatase, thus impairs lysosome-mediated pathogen clearance.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2017
Abstract: Circular RNAs (circRNAs) are a erse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.MOLMED.2013.05.001
Abstract: Inflammation is indispensable for host homeostasis against invading pathogens and efficient wound healing upon tissue malfunction and has to be tightly controlled by various mechanisms to limit excess responses harmful to host tissues. A myriad of disease conditions ranging from type 2 diabetes (T2D) to neurodegenerative and cardiovascular disorders are now shown to progress due to persistent, unresolved inflammation in metabolic tissues such as adipose, liver, pancreas, muscle, and brain. However, their underlying mechanisms are incompletely understood. The actions of innate and adaptive immune cells in these ailments are increasingly appreciated so much so that a new research area called 'immunometabolism' has emerged. In this review, we will highlight the fundamental roles of various immune cells in adipose tissue during the initiation and progression of obesity-induced inflammation and discuss potential anti-inflammatory therapies from different mechanistic points of view.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.MOLMED.2016.03.002
Abstract: Noncanonical NF-κB signaling differs from canonical NF-κB signaling by being activated through different cell surface receptors, cytoplasmic adaptors, and NF-κB dimers. Under normal physiological conditions, this noncanonical pathway has been implicated in erse biological processes, including lymphoid organogenesis, B cell maturation, osteoclast differentiation, and various functions of other immune cells. Recently, dysfunction of this pathway has also been causally associated with numerous immune-mediated pathologies and human malignancies. Here, we summarize the core elements as well as the recently identified novel regulators of the noncanonical NF-κB signaling pathway. The involvement of this pathway in different pathologies and the potential therapeutic options that are currently envisaged are also discussed.
Publisher: Rockefeller University Press
Date: 15-08-2017
DOI: 10.1084/JEM.20170910
Abstract: Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen–immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions. We bring to light recent discoveries and developments in mast cell research, including regulation of mast cell functions, differentiation, survival, and novel mouse models. Finally, we highlight the current and future opportunities for therapeutic intervention of mast cell functions in inflammatory diseases.
Publisher: Wiley
Date: 04-03-2021
DOI: 10.1002/LARY.29495
Abstract: The efficacy of short‐term oral corticosteroids in chronic rhinosinusitis without nasal polyps (CRSsNP) is unknown. The aim of this controlled study was to assess the immediate and long‐term outcomes from a short course of a commonly used oral corticosteroid, prednisolone, in well‐defined CRSsNP patients. Prospective, observational controlled study. A prospective‐controlled study of CRSsNP patients treated with prednisolone at 0.5 mg/kg tapered over 10 days and non‐prednisolone treated CRSsNP patients (controls) and follow‐up at 2, 6, and 12 months. Baseline and follow‐up SinoNasal Outcome Test (SNOT)‐22, nasal endoscopy (Lund‐Kennedy), and sinus CT scan scores (Lund‐Mackay) were compared. At 2 months, there was a significant improvement in the SNOT‐22, nasal endoscopy, and sinus CT scan scores in the prednisolone group ( P .0001) compared with controls (p = ns, Mann–Whitney U test). 52.5% of prednisolone‐treated CRSsNP patients had improved symptoms and did not require sinus surgery at 12 months compared with 14.3% of controls ( P .001). Side‐effects were reported in 8.9% of prednisolone‐treated patients. Patients who benefited from prednisolone had a median symptom duration of 7.25 (99% confidence, upper limit of 11) months compared with 18 months in those requiring surgery. Short‐term oral prednisolone significantly improved all three clinical measures of disease in CRSsNP patients and avoided surgical intervention in 52.5% patients in the first 12 months. Patients with symptoms for less than 11 months were most likely to benefit. The side‐effects of oral steroids require careful consideration and further studies are needed to ascertain appropriate dosage and treatment duration. 3 Laryngoscope , 131:E2618–E2626, 2021
Publisher: Springer Science and Business Media LLC
Date: 24-10-2020
Publisher: Cambridge University Press (CUP)
Date: 26-08-2022
DOI: 10.1017/S0022109021000570
Abstract: We investigate whether external industry tournament incentives influence the design of executive-compensation contracts. Using staggered negative mobility shocks as exogenous disruptions to tournament incentives, we show that firms treated by these shocks act to restore their executives’ diminished implicit risk-taking incentives by increasing compensation vega. On average, post-shock compensation vegas increase by approximately 10%. These effects are considerably larger for treated executives with strong tournament incentives and high ex ante mobility. Mobility shocks have no impact on compensation delta or total pay. Our results shed light on how explicit risk-taking incentives are optimized with respect to executive career concerns.
Publisher: Springer Science and Business Media LLC
Date: 06-1201
Publisher: Elsevier BV
Date: 07-2023
Publisher: Public Library of Science (PLoS)
Date: 23-09-2021
DOI: 10.1371/JOURNAL.PPAT.1009943
Abstract: Regulation of cellular metabolism is now recognized as a crucial mechanism for the activation of innate and adaptive immune cells upon erse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. Despite this dynamic interplay in host-pathogen interactions, the role of immunometabolism in the context of intracellular bacterial infections is still unclear. Here, employing unbiased metabolomic and transcriptomic approaches, we investigated the role of metabolic adaptations of macrophages upon Salmonella enterica serovar Typhimurium ( S . Typhimurium) infections. Importantly, our results suggest that S . Typhimurium abrogates glycolysis and its modulators such as insulin-signaling to impair macrophage defense. Mechanistically, glycolysis facilitates glycolytic enzyme aldolase A mediated v-ATPase assembly and the acidification of phagosomes which is critical for lysosomal degradation. Thus, impairment in the glycolytic machinery eventually leads to decreased bacterial clearance and antigen presentation in murine macrophages (BMDM). Collectively, our results highlight a vital molecular link between metabolic adaptation and phagosome maturation in macrophages, which is targeted by S . Typhimurium to evade cell-autonomous defense.
Publisher: Wiley
Date: 19-02-2021
DOI: 10.1111/IMCB.12440
Publisher: Wiley
Date: 06-02-2022
DOI: 10.1111/JELS.12305
Abstract: Excessive CEO power is often regarded as value‐destroying. We use a quasi‐exogenous regulatory shock to analyze whether improved governance helps to channel firms with powerful CEOs toward more value‐enhancing corporate policies. We use the Sarbanes‐Oxley Act and NYSE/NASDAQ listing rules and focus on firms that were required to improve governance. We find that postregulation firms led by powerful CEOs increase innovation inputs (Research and Development expenditures) and produce more innovation outputs (patents) that are scientifically more important (citations) and economically more valuable (market value of patents). Investment quality also improves, manifesting in better takeover performance and improvements in firm performance and corporate value. Our results suggest that improved governance can mitigate value destruction in powerful CEO‐managed firms. We take steps to mitigate econometric concerns and ensure our results are robust to various combinations of fixed effects and control variables.
No related grants have been discovered for GOKHAN CILDIR.