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Isak Demirel

Position: Senior Lecturer School/office: School of Medical Sciences

Room: X2104

Research subject

Biomedicine

About Isak Demirel

Isak Demirel is a Senior Lecturer in Biomedicine at the Department of Medical Sciences. He defended his thesis in 2014 at the Department of Medical Sciences. The thesis was focused on characterising the host-pathogen interaction of uropathogenic Escherichia coli (UPEC) during a urinary tract infection. During the latter part of his studies, the aim was to investigate if the immune response evoked by extended spectrum beta lactamase (ESBL) isolates differs from non-ESBL-producing uropathogenic E. coli. His research aimed to characterize the virulence patterns of ESBL isolates and to identify new novel treatment options to cope with the globally increased antibiotic resistance. Isak Demirel was appointed as Associate Professor (Docent) in Biomedicine in 2019 and leads the "infection & inflammation research group".

Research profile

Isak Demirels research interests are in the field of host-pathogen interaction and kidney disease. Isak Demirel is the main supervisor of four ongoing PhD students: Anna Lindblad (leg. BMA), Carolina Pettersson (leg. BMA) Stefania Kapetanaki (Leg. MD) and Anna Magnusson (Leg. Dentist).

Key questions of interest:

1. How does uropathogenic E. coli interact with the urinary tract and which virulence factors does the bacteria use to colonize the bladder?

2. How does renal fibroblast contribute to the host response during a urinary tract infection?

3. Can miRNA be used as a novel alternative treatment against multi-drug resistant uropathogenic E. coli?

4. What impact does proinflammatory cytokines and hormones have on the virulence of uropathogenic E. coli and Porphyromonas gingivalis?

5. How does Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans contribute to oral-and systemic disease?

6. How does the microbiota-generated metabolite TMAO contribute to the development of kidney disease?

Teaching and Administrative assignments

Isak Demirel is teaching at the medical school and the international master’s program in biomedicine at the department of medical sciences in different subject within biomedicine (microbiology, immunology, and cell biology).

Isak Demirel is the Unit head of unit “gastro-endocrino and urologic science” at the department of medical sciences and an Editorial board member of Scientific reports.

Active projects

Research groups

Publications

Articles in journals

Pettersson, C. , Wu, R. & Demirel, I. (2024). Estrogen-stimulated uropathogenic E. coli mediate enhanced neutrophil responses. Scientific Reports, 14 (1). [BibTeX]
Magnusson, A. , Wu, R. & Demirel, I. (2024). Porphyromonas gingivalis triggers microglia activation and neurodegenerative processes through NOX4. Frontiers in Cellular and Infection Microbiology, 14. [BibTeX]
Wu, R. , Pettersson, C. & Demirel, I. (2024). Testosterone increases the virulence traits of uropathogenic Escherichia coli. Frontiers in Microbiology, 15. [BibTeX]
Kapetanaki, S. , Kumawat, A. K. , Paramel Varghese, G. , Persson, K. & Demirel, I. (2024). TMAO enhances TNF-α mediated fibrosis and release of inflammatory mediators from renal fibroblasts. Scientific Reports, 14 (1). [BibTeX]
Thazhathveettil, J. , Kumawat, A. K. , Demirel, I. , Sirsjö, A. & Paramel Varghese, G. (2024). Vascular smooth muscle cells in response to cholesterol crystals modulates inflammatory cytokines release and promotes neutrophil extracellular trap formation. Molecular Medicine, 30 (1). [BibTeX]
Mohanty, S. , Lindelauf, C. , White, J. K. , Scheffschick, A. , Ehrenborg, E. , Demirel, I. , Brauner, H. & Brauner, A. (2023). Inhibition of COX-2 signaling favors E. coli during urinary tract infection. Journal of Inflammation, 20 (1). [BibTeX]
Wenglén, C. , Demirel, I. , Göthlin Eremo, A. , Grenegård, M. & Paramel Varghese, G. (2023). Targeting serotonin receptor 2B inhibits TGFβ induced differentiation of human vascular smooth muscle cells. European Journal of Pharmacology, 944. [BibTeX]
Jayaprakash Demirel, K. , Wu, R. , Neves Guimaraes, A. & Demirel, I. (2023). The role of NLRP3 in regulating gingival epithelial cell responses evoked by Aggregatibacter actinomycetemcomitans. Cytokine, 169. [BibTeX]
Lindblad, A. , Wu, R. , Persson, K. & Demirel, I. (2023). The Role of NLRP3 in Regulation of Antimicrobial Peptides and Estrogen Signaling in UPEC-Infected Bladder Epithelial Cells. Cells, 12 (18). [BibTeX]
Wu, R. , Kumawat, A. K. & Demirel, I. (2023). Trimethylamine N-Oxide (TMAO) Mediates Increased Inflammation and Colonization of Bladder Epithelial Cells during a Uropathogenic E. coli Infection In Vitro. Pathogens, 12 (4). [BibTeX]
Williams, B. M. , Cliff, C. L. , Demirel, I. , Squires, P. E. & Hills, C. E. (2022). Blocking connexin-43 hemichannel-mediated ATP release reduces communication within and between tubular epithelial cells and medullary fibroblasts in a model of diabetic nephropathy. Diabetic Medicine, 39 (12). [BibTeX]
Jayaprakash Demirel, K. , Neves Guimaraes, A. & Demirel, I. (2022). Effects of estradiol on the virulence traits of Porphyromonas gingivalis. Scientific Reports, 12 (1). [BibTeX]
Lindblad, A. , Johansson, C. , Persson, K. & Demirel, I. (2022). The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli. Scientific Reports, 12 (1). [BibTeX]
Kapetanaki, S. , Kumawat, A. K. , Persson, K. & Demirel, I. (2022). TMAO Suppresses Megalin Expression and Albumin Uptake in Human Proximal Tubular Cells Via PI3K and ERK Signaling. International Journal of Molecular Sciences, 23 (16). [BibTeX]
Persson, K. , Petersson, U. , Johansson, C. , Demirel, I. & Kruse, R. (2022). Transcriptional alterations in bladder epithelial cells in response to infection with different morphological states of uropathogenic Escherichia coli. Scientific Reports, 12 (1). [BibTeX]
Engelsöy, U. , Svensson, M. & Demirel, I. (2021). Estradiol Alters the Virulence Traits of Uropathogenic Escherichia coli. Frontiers in Microbiology, 12. [BibTeX]
Kumawat, A. K. , Paramel Varghese, G. , Jayaprakash, K. & Demirel, I. (2021). Human Renal Fibroblasts, but Not Renal Epithelial Cells, Induce IL-1β Release during a Uropathogenic Escherichia coli Infection In Vitro. Cells, 10 (12). [BibTeX]
Kapetanaki, S. , Kumawat, A. K. , Persson, K. & Demirel, I. (2021). The Fibrotic Effects of TMAO on Human Renal Fibroblasts Is Mediated by NLRP3, Caspase-1 and the PERK/Akt/mTOR Pathway. International Journal of Molecular Sciences, 22 (21). [BibTeX]
Demirel, I. , Persson, A. , Brauner, A. , Särndahl, E. , Kruse, R. & Persson, K. (2020). Activation of NLRP3 by uropathogenic Escherichia coli is associated with IL-1β release and regulation of antimicrobial properties in human neutrophils. Scientific Reports, 10 (1). [BibTeX]
Klarström-Engström, K. , Zhang, B. & Demirel, I. (2019). Human renal fibroblasts are strong immunomobilizers during a urinary tract infection mediated by uropathogenic Escherichia coli. Scientific Reports, 9 (1). [BibTeX]
Lindblad, A. , Persson, K. & Demirel, I. (2019). IL-1RA is part of the inflammasome-regulated immune response in bladder epithelial cells and influences colonization of uropathogenic E. coli. Cytokine, 123. [BibTeX]
Engelsöy, U. , Rangel, I. & Demirel, I. (2019). Impact of Proinflammatory Cytokines on the Virulence of Uropathogenic Escherichia coli. Frontiers in Microbiology, 10. [BibTeX]
Asfaw Idosa, B. , Kelly, A. , Jacobsson, S. , Demirel, I. , Fredlund, H. , Särndahl, E. & Persson, A. (2019). Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent. Journal of Immunology Research. [BibTeX]
Demirel, I. , Persson, A. , Brauner, A. , Särndahl, E. , Kruse, R. & Persson, K. (2018). Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells. Frontiers in Cellular and Infection Microbiology, 8. [BibTeX]
Lönn, J. , Ljunggren, S. , Klarström-Engström, K. , Demirel, I. , Bengtsson, T. & Karlsson, H. (2018). Lipoprotein modifications by gingipains of Porphyromonas gingivalis. Journal of Periodontal Research, 53 (3), 403-413. [BibTeX]
Jayaprakash, K. , Demirel, I. , Khalaf, H. & Bengtsson, T. (2018). Porphyromonas gingivalis-induced inflammatory responses in THP1 cells are altered by native and modified low-density lipoproteins in a strain-dependent manner. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 126 (8), 667-677. [BibTeX]
Månsson, E. , Söderquist, B. , Nilsdotter-Augustinsson, Å. , Särndahl, E. & Demirel, I. (2018). Staphylococcus epidermidis from prosthetic joint infections induces lower IL-1 release from human neutrophils than isolates from normal flora. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 126 (8), 678-684. [BibTeX]
Bang, C. S. , Demirel, I. , Kruse, R. & Persson, K. (2017). Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli. PLOS ONE, 12 (6). [BibTeX]
Jayaprakash, K. , Demirel, I. , Gunaltay, S. , Khalaf, H. & Bengtsson, T. (2017). PKC, ERK/p38 MAP kinases and NF-B targeted signalling play a role in the expression and release of IL-1β and CXCL8 in Porphyromonas gingivalis-infected THP1 cells. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 125 (7), 623-633. [BibTeX]
Palm, E. , Demirel, I. , Bengtsson, T. & Khalaf, H. (2017). The role of toll-like and protease-activated receptors and associated intracellular signaling in Porphyromonas gingivalis-infected gingival fibroblasts. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 125 (2), 157-169. [BibTeX]
Demirel, I. , Rangel, I. , Petersson, U. , Persson, K. & Kruse, R. (2017). Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL)-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics. Frontiers in Microbiology, 8. [BibTeX]
Demirel, I. , Kruse, R. , Önnberg, A. & Persson, K. (2015). Ceftibuten-induced filamentation of extended spectrum beta lactamase (ESBL)-producing uropathogenic Escherichia coli alters host cell responses during an in vitro infection. Microbial Pathogenesis, 78, 52-62. [BibTeX]
Jayaprakash, K. , Demirel, I. , Khalaf, H. & Bengtsson, T. (2015). The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis. Molecular Oral Microbiology, 30 (5), 361-375. [BibTeX]
Palm, E. , Demirel, I. , Bengtsson, T. & Khalaf, H. (2015). The role of toll-like and protease-activated receptors in the expression of cytokines by gingival fibroblasts stimulated with the periodontal pathogen Porphyromonas gingivalis. Cytokine, 76 (2), 424-432. [BibTeX]
Kruse, R. , Demirel, I. , Säve, S. & Persson, K. (2014). IL-8 and global gene expression analysis define a key role of ATP in renal epithelial cell responses induced by uropathogenic bacteria. Purinergic Signalling Purinergic Signalling, 10 (3), 499-508. [BibTeX]
Bang, C. S. , Kruse, R. , Demirel, I. , Önnberg, A. , Söderquist, B. & Persson, K. (2014). Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).. Microbial Pathogenesis, 66, 29-35. [BibTeX]
Demirel, I. , Kinnunen, A. , Önnberg, A. , Söderquist, B. & Persson, K. (2013). Comparison of host response mechanisms evoked by extended spectrum beta lactamase (ESBL)- and non-ESBL-producing uropathogenic E. coli. BMC Microbiology, 13. [BibTeX]
Demirel, I. , Säve, S. , Kruse, R. & Persson, K. (2013). Expression of suppressor of cytokine signalling 3 (SOCS3) in human bladder epithelial cells infected with uropathogenic Escherichia coli. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 121 (2), 158-167. [BibTeX]
Khalaf, H. , Demirel, I. & Bengtsson, T. (2013). Suppression of inflammatory gene expression in T cells by Porphyromonas gingivalis is mediated by targeting MAPK signaling. Cellular & Molecular Immunology, 10 (5), 413-422. [BibTeX]
Demirel, I. , Vumma, R. , Mohlin, C. , Svensson, L. , Säve, S. & Persson, K. (2012). Nitric oxide activates IL-6 production and expression in human renal epithelial cells. American Journal of Nephrology, 36 (6), 524-530. [BibTeX]

Articles, reviews/surveys

Svensson, L. , Poljakovic, M. , Demirel, I. , Sahlberg, C. & Persson, K. (2018). Host-Derived Nitric Oxide and Its Antibacterial Effects in the Urinary Tract. Advances in Microbial Physiology, 73, 1-62. [BibTeX]

Conference papers

Thazhathveettil, J. , Kumawat, A. , Demirel, I. , Sirsjö, A. & Paramel, G. (2023). Cholesterol crystals uptake in vascular smooth muscle cells modulates local immune responses. In: Atherosclerosis. Paper presented at 91st Annual Meeting of the European-Atherosclerosis-Society (EAS 2023), Mannheim, Germany, May 21-24, 2023. (pp. S9-S9). Elsevier. [BibTeX]
Kurt, S. , Pirronello, F. , Reitsema, R. , Demirel, I. , Rangel, I. , Sirsjö, A. , Dreifaldt, M. & Kumawat, A. (2023). Increased proportion of circulating neutrophils with impaired phagocytosis capacity in patients with peripheral arterial disease. In: Atherosclerosis. Paper presented at 91st Annual Meeting of the European-Atherosclerosis-Society (EAS 2023), Mannheim, Germany, May 21-24, 2023. (pp. S22-S22). Elsevier. [BibTeX]
Williams, B. M. , Cliff, C. L. , Demirel, I. , Squires, P. E. & Hills, C. E. (2022). Connexin-43 hemichannel mediated ATP release stimulates fibroblast activation in an in vitro model of diabetic kidney disease. In: Diabetic Medicine. Paper presented at Diabetes UK Professional Conference 2022, (Online conference), London, UK, March 28 - April 1, 2022. John Wiley & Sons. [BibTeX]

Doctoral theses, comprehensive summaries

Demirel, I. (2014). Uropathogenic Esherichia coli, multidrug-resistance and induction of host defense mechanisms. (Doctoral dissertation). (Comprehensive summary) Örebro: Örebro universitet. [BibTeX]

Manuscripts

Demirel, I. , Kruse, R. , Önnberg, A. & Persson, K. Antibiotic-induced filamentation of extended spectrum beta lactamase (ESBL)-producing uropathogenic E. coli alters host cell responses during an in vitro infection. [BibTeX]
Lindblad, A. , Persson, K. & Demirel, I. Caspase-1 and caspase-4 affect gene expression of host defense factors inUPEC-infected bladder epithelial cells. [BibTeX]
Asfaw Idosa, B. , Persson, A. , Jacobsson, S. , Demirel, I. , Fredlund, H. , Särndahl, E. & Kelly, A. LOS-dependent Neisseria meningitidis-induced caspase-1 activation in human neutrophils. [BibTeX]
Jayaprakash, K. , Demirel, I. , Gunaltay, S. , Khalaf, H. & Bengtsson, T. PKC, ERK/p38 MAP kinases and NF-κB targeted signalling plays a crucial role in expression and release of IL-1β and CXCL8 in Porphyromonas gingivalis infected monocytes. [BibTeX]
Jayaprakash, K. , Demirel, I. , Khalaf, H. & Bengtsson, T. Porphyromonas gingivalis induced release of reactive oxygen species and interleukin-1 beta and the effects of low density lipoproteins in monocytes and whole blood. [BibTeX]
Palm, E. , Demirel, I. , Bengtsson, T. & Khalaf, H. The role of toll-like and protease-activated receptors and associated intracellular signalling in Porphyromonas gingivalis-infected gingival fibroblasts. [BibTeX]
Palm, E. , Demirel, I. , Bengtsson, T. & Khalaf, H. The role of toll-like and protease-activated receptors in the expression of cytokines by gingival fibroblasts stimulated with the periodontal pathogen Porphyromonas gingivalis. [BibTeX]