Browsing by Author "Gündüz, Nuray"

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Open Access
Biotin functionalized self‐assembled peptide nanofiber as an adjuvant for immunomodulatory response
(Wiley-VCH Verlag, 2020-12) Demircan, Muhammed Burak; Tohumeken, Sehmus; Gündüz, Nuray; Khalily, Mohammad Aref; Tekinay, T.; Güler, M. O.; Tekinay, Ayşe B.
Biotinylated peptide amphiphile (Biotin‐PA) nanofibers, are designed as a noncovalent binding location for antigens, which are adjuvants to enhance, accelerate, and prolong the immune response triggered by antigens. Presenting antigens on synthetic Biotin‐PA nanofibers generated a higher immune response than the free antigens delivered with a cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODN) (TLR9 agonist) adjuvant. Antigen attached Biotin‐PA nanofibers trigger splenocytes to produce high levels of cytokines (IFN‐γ, IL‐12, TNF‐α, and IL‐6) and to exhibit a superior cross‐presentation of the antigen. Both Biotin‐PA nanofibers and CpG ODN induce a Th‐1‐biased IgG subclass response; however, delivering the antigen with Biotin‐PA nanofibers induce significantly greater production of total IgG and subclasses of IgG compared to delivering the antigen with CpG ODN. Contrary to CpG ODN, Biotin‐PA nanofibers also enhance antigen‐specific splenocyte proliferation and increase the proportion of the antigen‐specific CD8(+) T cells. Given their biodegradability and biocompatibility, Biotin‐PA nanofibers have a significant potential in immunoengineering applications as a biomaterial for the delivery of a diverse set of antigens derived from intracellular pathogens, emerging viral diseases such as COVID‐19, or cancer cells to induce humoral and cellular immune responses against the antigens.
Open Access
Ketone body signaling mediates intestinal stem cell homeostasis and adaptation to diet
(Cell Press, 2019) Cheng, C.-W.; Biton, M.; Haber, A. L.; Gündüz, Nuray; Eng, G.; Gaynor, L. T.; Tripathi, S.; Çalıbaşı-Koçal, G.; Rickelt, S.; Butty, V. L.; Moreno-Serrano, M.; Iqbal, A. M.; Bauer-Rowe, K. E.; Imada, S.; Ulutaş, M. S.; Mylonas, C.; Whary, M. T.; Levine, S. S.; Başbınar, Y.; Hynes, R. O.; Mino-Kenudson, M.; Deshpande, V.; Boyer, L. A.; Fox, J. G.; Terranova, C.; Rai, K.; Piwnica-Worms, H.; Mihaylova, M. M.; Regev, A.; Yılmaz, Ö. H.
Little is known about how metabolites couple tissue-specific stem cell function with physiology. Here we show that, in the mammalian small intestine, the expression of Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2), the gene encoding the rate-limiting enzyme in the production of ketone bodies, including beta-hydroxybutyrate (βOHB), distinguishes self-renewing Lgr5 + stem cells (ISCs) from differentiated cell types. Hmgcs2 loss depletes βOHB levels in Lgr5 + ISCs and skews their differentiation toward secretory cell fates, which can be rescued by exogenous βOHB and class I histone deacetylase (HDAC) inhibitor treatment. Mechanistically, βOHB acts by inhibiting HDACs to reinforce Notch signaling, instructing ISC self-renewal and lineage decisions. Notably, although a high-fat ketogenic diet elevates ISC function and post-injury regeneration through βOHB-mediated Notch signaling, a glucose-supplemented diet has the opposite effects. These findings reveal how control of βOHB-activated signaling in ISCs by diet helps to fine-tune stem cell adaptation in homeostasis and injury. Graphical Abstract
Open Access
Molecular analysis of enginereed nanomaterials in biomedical and regenerative medicine applications
(2019-04) Gündüz, Nuray
Molecular mechanisms are inspiration source for effective nanomaterial synthesis through minimalist bottom-up approaches. Mimicking functional biophysicochemical properties of biomacromolecules can give new insights for design and synthesis of nanomaterials used in biomedical and regenerative medicine applications. In this thesis, rationally-designed nanomaterials and their biomedical applications as oral ketone delivery and biomineralization and long-term potential toxicities were investigated. In the first chapter, basic concepts of nanomaterial design, synthesis, characterization, and nano-bio interface were explained. In the second chapter, a novel long-term nanoparticle accumulation model was developed to understand active regulation of nanoparticle uptake, nanoparticle accumulation behavior and the impact of long-term exposure on cellular machineries (e.g. ER stress). In the third chapter, the role of ketone body betahydroxybutryrate (βOHB) generated by a metabolic enzyme, hydroxymethylglutaryl CoA synthase 2 (HMGCS2), on intestinal stem cell maintenance and regeneration after radiation injury was investigated. Consequences of βOHB depletion in intestine were rectified by oral delivery of PLGA-encapsulated and oligomer forms of βOHB. The last chapter, acidic epitopes of enamel proteins (e.g. amelogenin) were integrated into self-assembling peptides to remineralize eroded enamel. Overall these studies show potential of natureinspired engineered nanomaterials in vast range of biomedical and regenerative medicine applications.
Open Access
Safety of nanomaterials
(John Wiley & Sons, 2016-03-11) Gündüz, Nuray; Arslan, Elif; Güler, Mustafa O.; Tekinay, Ayşe B.; Güler, Mustafa O.; Tekinay, Ayşe B.
This chapter overviews the attempts in understanding the biocompatibility of nanomaterials and provides an account of how these views changed in light of recent findings, with emphasis on the methodology used in nanotoxicology studies. The excretion and clearance of engineered nanomaterials (ENMs) is discussed in the chapter, but it should be noted that cells themselves respond to ENMs by activating their exocytosis mechanisms, thus extruding or degrading ENMs at the subcellular level. Although the in vitro tests previously outlined in the chapter provide means of predicting the behavior of nanomaterials, it is nonetheless possible that unforeseen in vivo effects may occur. As with any material intended for human use, their safety must first and foremost be investigated to sufficient detail, through both in vitro experiments and animal studies, before they can be administered to human patients.