Welcome to the Koç University Institutional Academic Repository
The Koç University Institutional Academic Repository (KUHub Research) is a state-of-the-art academic repository that consolidates all academic outputs—such as articles, conference proceedings, theses, research data, and more—produced by the university since its establishment in 1993.
KUHub Research adheres to the principles of Open Access and FAIR (Findable, Accessible, Interoperable, Reusable), providing access to the bibliographic records, research data, and full texts of research outputs. Equipped with innovative features such as Author Profile pages and enhanced tools, KUHub Research aims to enhance the visibility of researchers both nationally and internationally. KUHub Research aims to preserve and maintain Koç University's valuable academic legacy for future generations while also serving the needs of today’s researchers.
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Recent Submissions
Mechanisms of fast CO2 fixation reaction by enoyl-CoA carboxylases/reductase
(European Synchrotron Radiation Facility, 2028-01-01) Chretien, Anaïs; Ertem Kuzucu, Fatma Betul; Summers, Jacob; Wranik, Maximilian; 0000-0001-8480-1443; 0000-0002-2144-989x; 0000-0003-3113-0353; 0000-0002-2482-0164
Carbon dioxide (CO2) is an atmospheric greenhouse gas that feeds all life, plays a critical role in global warming, and could constitute an inexpensive carbon source for future sustainable industries. While synthetic chemistry lacks suitable catalysts to functionalize carbon dioxide in mild reaction conditions, autotrophs do it constantly, and thus there is increasing interest in exploiting the CO2-fixation mechanisms offered by nature. In this exchange proposal, we propose fast time-resolved structural-dynamics studies of one of the fastest CO2-fixation enzymes, enoyl-CoA carboxylase/reductase (ECR), using ambient temperature serial X-ray crystallography on Beamline ID29, ESRF, which achieves 10μs resolution. This study will reveal details of the enzyme subunit coupling as well as the enzyme-substrate interactions to correlate the structural and functional states of the enzyme during fixation and pave the way for faster biomolecule productions using engineered C-cycling enzymes.
Mechanisms of fast CO2 fixation reaction by enoyl-CoA carboxylases/reductase
(European Synchrotron Radiation Facility, 2027-01-01) Summers, Jacob; Sanctis, Daniele; Vlahakis, Niko; Knight, Victoria; Ertem Kuzucu, Fatma Betul; Chretien, Anaïs; Nurizzo, Didier; 0000-0003-3113-0353; 0000-0003-0391-8290; 0000-0002-5092-0265; 0000-0002-2144-989x; 0000-0001-8480-1443; 0000-0002-7367-5098
Carbon dioxide (CO2) is an atmospheric greenhouse gas that feeds all life, plays a critical role in global warming, and could constitute an inexpensive carbon source for future sustainable industries. While synthetic chemistry lacks suitable catalysts to functionalize carbon dioxide in mild reaction conditions, autotrophs do it constantly, and thus there is increasing interest in exploiting the CO2-fixation mechanisms offered by nature. In this exchange proposal, we propose fast time-resolved structural-dynamics studies of one of the fastest CO2-fixation enzymes, enoyl-CoA carboxylase/reductase (ECR), using ambient temperature serial X-ray crystallography on Beamline ID29, ESRF, which achieves 10μs resolution. This study will reveal details of the enzyme subunit coupling as well as the enzyme-substrate interactions to correlate the structural and functional states of the enzyme during fixation and pave the way for faster biomolecule productions using engineered C-cycling enzymes.
Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry
(Springer Science and Business Media LLC, 2026-02-01) Altıntaş, Ayşe; Souissi, Amira; Patti, Francesco; Spelman, Tim; Chisari, Clara; Gargouri, Amina; John, Nevin; Kermode, Allan G.; Kalincik, Tomas; Butzkueven, Helmut; Sajedi, Seyed Aidin; Lechner-Scott, Jeannette; Roos, Izanne; Laureys, Guy; Taylor, Bruce; Alroughani, Raed; Khoury, Samia J.; Macdonell, Richard; Weinstock-Guttman, Bianca; Havrdova, Eva Kubala; Maimone, Davide; Reddel, Stephen; Fabis-Pedrini, Marzena; Willekens, Barbara; Moghadasi, Abdorreza Naser; Lalive, Patrice; Lugaresi, Alessandra; Ozakbas, Serkan; Solaro, Claudio; Cárdenas-Robledo, Simón; Shaygannejad, Vahid; Etemadifar, Masoud; Boz, Cavit; Eichau, Sara; Tomassini, Valentina; Terzi, Murat; Prat, Alexandre; Habek, Mario; Blanco, Yolanda; Gerlach, Oliver; Turkoglu, Recai; Buzzard, Katherine; Skibina, Olga; Soysal, Aysun; van der Walt, Anneke; Hughes, Stella; van Pesch, Vincent; Foschi, Matteo; Surcinelli, Andrea; Prevost, Julie; Ramo-Tello, Cristina; McGuigan, Chris; Sa, Maria Jose; Kuhle, Jens; Spitaleri, Daniele; Singhal, Bhim; Ampapa, Radek; de Gans, Koen; Petersen, Thor; Simu, Mihaela; Lapointe, Emmanuelle; Sanchez-Menoyo, Jose Luis; Gray, Orla; Garber, Justin; Aguera-Morales, Eduardo; Gross-Paju, Katrin; Castillo-Triviño, Tamara; Al-Asmi, Abdullah; Grigoriadis, Nikolaos; Inshasi, Jihad; Al-Harbi, Talal; Hardy, Todd A.; Ramanathan, Sudarshini; Cambron, Melissa; Shuey, Neil; sempere, Angel Perez; Csepany, Tunde; Treviño-Frenk, Irene; Rozsa, Csilla; Cauchi, Marija; Karabudak, Rana; Mrabet, Saloua; Gouider, Riadh; School of Medicine; KUTTAM (Koç University Research Center for Translational Medicine); Yes; SCHOOL OF MEDICINE; Research Center
Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS).We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18-39 years), transition onset (40-49 years), LOMS (50-59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions.Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93).LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.
Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape
(Springer, 2026) Adsay, Nazmi Volkan; Bevere, M.; Gkountakos, A.; Valentinuzzi, S.; De Fabritiis, S.; Wong, C. S.; De Robertis, R.; Mattiolo, P.; Gentiluomo, M.; Fassan, M.; Pea, A.; Crinò, S. F.; Simbolo, M.; Mafficini, A.; Campa, D.; Cingarlini, S.; Landoni, L.; Lawlor, R. T.; Salvia, R.; D’Onofrio, M.; Milella, M.; Brosens, L. A.; Heaphy, C. M.; Hong, S.; Singhi, A. D.; Scarpa, A.; Luchini, C.; School of Medicine; KUTTAM (Koç University Research Center for Translational Medicine); KUH (KOÇ UNIVERSITY HOSPITAL); Research Center
Pancreatic neuroendocrine neoplasms (PanNENs) constitute a heterogeneous group of tumors distinguished by substantial variability in morphology, immunophenotype, molecular characteristics, and clinical behavior. In recent years, the advent of multiple omics-based methodologies has significantly enhanced our understanding of these neoplasms. Integrating histology and genomics with survival analyses has clarified that the fundamental distinction within this disease spectrum lies between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Furthermore, genomics, transcriptomics, and epigenetic profiling have deepened the granularity of the PanNET landscape, revealing marked differences even within the same diagnostic category, with important clinical implications. For example, DAXX / ATRX mutations, activation of the alternative lengthening of telomeres pathway, BEND2 gene fusions, and an α-cell transcriptional profile are more frequently associated with adverse outcomes. Additional omics approaches, including metabolomics, proteomics, radiomics, and the more recently developed spatially resolved methodologies, are further expanding current knowledge in this challenging field. In this review, we provide an integrated overview of PanNENs, synthesizing insights generated across diverse multi-omics platforms. Graphical abstract This review offers a comprehensive and integrative synthesis of the principal findings across histology, genomics, transcriptomics, epigenetics, metabolomics, proteomics, and radiomics in pancreatic neuroendocrine neoplasms. By integrating multiple omics layers, it advances a more holistic and in-depth characterization of these neoplasms, thereby enhancing the current understanding of their biological complexity.
Prognostic value of the aggregate index of systemic inflammation in predicting in-hospital adverse outcomes among patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention
(Springer, 2026) Parsova, Kemal Emrecan; Kahraman, E.; Durak, F.; Gumusdag, A.; Iskender, H.; Cakir, B.; Velibey, Y.; KUH (Koç University Hospital); KUH (KOÇ UNIVERSITY HOSPITAL)
Inflammation plays a pivotal role in the initiation and progression of atherosclerosis and acute coronary syndromes. The Aggregate Index of Systemic Inflammation (AISI), a novel biomarker derived from neutrophil, monocyte, platelet, and lymphocyte counts, reflects the systemic inflammatory response. Although AISI has demonstrated prognostic value in various cardiovascular settings, its utility in its association with in-hospital adverse outcomes among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) remains unclear. This study aimed to evaluate whether AISI reflects systemic inflammatory burden and its association with in-hospital adverse outcomes in STEMI patients undergoing primary PCI. Materials and methods This retrospective, single-center study included 2,678 consecutive STEMI patients who underwent primary PCI. AISI was calculated as (neutrophil × monocyte × platelet) / lymphocyte, and patients were stratified into high and low AISI groups according to the median value. The primary outcomes were in-hospital mortality and major adverse cardiac and cerebrovascular events (MACCE). Secondary endpoints included arrhythmic complications, acute stent thrombosis, and ischemic stroke. Results Patients with high AISI were older, had higher rates of diabetes and hypertension, elevated glucose and creatinine, and lower left ventricular ejection fraction. High AISI was associated with mortality and MACCE in univariate analyses, whereas continuous AISI showed only a statistically significant but clinically modest association after multivariable adjustment when expressed per 100-unit increase. These findings indicate that AISI has limited standalone prognostic value and should be interpreted as an adjunctive inflammatory marker. Elevated AISI showed an independent association with ischemic stroke (adjusted OR = 4.77, 95% CI 1.02–22.30, p = 0.047); however, this finding should be interpreted cautiously given the low number of events and wide confidence intervals. ROC analysis showed moderate discriminative performance for in-hospital mortality (AUC = 0.64), MACCE (AUC = 0.60), and ischemic stroke (AUC = 0.70). Conclusion AISI is a simple, cost-effective inflammatory marker that may aid in risk stratification for in-hospital adverse and cerebrovascular outcomes in STEMI patients undergoing primary PCI.