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Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2
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Publication Open Access Androgen receptor-mediated transcription in prostate cancer(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Morova, Tunç; Department of Computer Engineering; Department of Chemical and Biological Engineering; Lack, Nathan Alan; Özturan, Doğancan; Faculty Member; PhD Student; Department of Computer Engineering; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 120842; N/AAndrogen receptor (AR)-mediated transcription is critical in almost all stages of prostate cancer (PCa) growth and differentiation. This process involves a complex interplay of coregulatory proteins, chromatin remodeling complexes, and other transcription factors that work with AR at cis-regulatory enhancer regions to induce the spatiotemporal transcription of target genes. This enhancer-driven mechanism is remarkably dynamic and undergoes significant alterations during PCa progression. In this review, we discuss the AR mechanism of action in PCa with a focus on how cis-regulatory elements modulate gene expression. We explore emerging evidence of genetic variants that can impact AR regulatory regions and alter gene transcription in PCa. Finally, we highlight several outstanding questions and discuss potential mechanisms of this critical transcription factor.Publication Open Access Development, characterization, and hematopoietic differentiation of Griscelli syndrome type 2 induced pluripotent stem cells(BioMed Central, 2021) Güney-Esken, Gülen; Erol, Özgür Doğuş; Pervin, Burcu; Korkusuz, Petek; Günel-Özcan, Ayşen; Uçkan-Çetinkaya, Duygu; Aerts-Kaya, Fatima; Sevinç, Gülben Gürhan; Önder, Tamer Tevfik; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 42946Background: Griscelli syndrome type 2 (GS-2) is a rare, autosomal recessive immune deficiency syndrome caused by a mutation in the RAB27A gene, which results in the absence of a protein involved in vesicle trafficking and consequent loss of function of in particular cytotoxic T and NK cells. Induced pluripotent stem cells (iPSC) express genes associated with pluripotency, have the capacity for infinite expansion, and can differentiate into cells from all three germ layers. They can be induced using integrative or non-integrative systems for transfer of the Oct4, Sox2, Klf4, and cMyc (OSKM) transcription factors. To better understand the pathophysiology of GS-2 and to test novel treatment options, there is a need for an in vitro model of GS-2. Methods: here, we generated iPSCs from 3 different GS-2 patients using lentiviral vectors. The iPSCs were characterized using flow cytometry and RT-PCR and tested for the expression of pluripotency markers. In vivo differentiation to cells from all three germlines was tested using a teratoma assay. In vitro differentiation of GS-2 iPSCs into hematopoietic stem and progenitor cells was done using Op9 feeder layers and specified media. Results: all GS-2 iPSC clones displayed a normal karyotype (46XX or 46XY) and were shown to express the same RAB27A gene mutation that was present in the original somatic donor cells. GS-2 iPSCs expressed SSEA1, SSEA4, TRA-1-60, TRA-1-81, and OCT4 proteins, and SOX2, NANOG, and OCT4 expression were confirmed by RT-PCR. Differentiation capacity into cells from all three germ layers was confirmed using the teratoma assay. GS-2 iPSCs showed the capacity to differentiate into cells of the hematopoietic lineage. Conclusions: using the lentiviral transfer of OSKM, we were able to generate different iPSC clones from 3 GS-2 patients. These cells can be used in future studies for the development of novel treatment options and to study the pathophysiology of GS-2 disease.
Publication Metadata only Progress Study: progression of chronic kidney disease in children and heat shock proteins(SPRINGER, 2021) Yürük Yıldırım, Zeynep Nagehan; Usta Akgül, Sebahat; Alpay, Harika; Aksu, Bağdagül; Savran Oğuz, Fatma; Kıyak, Aysel; Akıncı, Nurver; Yavuz, Sevgi; Özçelik, Gül; Gedikbaşı, Asuman; Gökçe, İbrahim; Özkayın, Neşe; Yıldız, Nurdan; Pehlivanoğlu, Cemile; Göknar, Nilüfer; Saygılı, Seha; Tülpar, Sebahat; Küçük, Nuran; Ağbaş, Ayşe; Dirican, Ahmet; Emre, Sevinç; Nayir, Ahmet; Yolmaz, Alev; Bilge, İlmay; Taşdemir, Mehmet; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 198907; 175867Various molecular and cellular processes are involved in renal fibrosis, such as oxidative stress, inflammation, endothelial cell injury, and apoptosis. Heat shock proteins (HSPs) are implicated in the progression of chronic kidney disease (CKD). Our aim was to evaluate changes in urine and serum HSP levels over time and their relationships with the clinical parameters of CKD in children. In total, 117 children with CKD and 56 healthy children were examined. The CKD group was followed up prospectively for 24 months. Serum and urine HSP27, HSP40, HSP47, HSP60, HSP70, HSP72, and HSP90 levels and serum anti-HSP60 and anti-HSP70 levels were measured by ELISA at baseline, 12 months, and 24 months. The urine levels of all HSPs and the serum levels of HSP40, HSP47, HSP60, HSP70, anti-HSP60, and anti-HSP70 were higher at baseline in the CKD group than in the control group. Over the months, serum HSP47 and HSP60 levels steadily decreased, whereas HSP90 and anti-HSP60 levels steadily increased. Urine HSP levels were elevated in children with CKD; however, with the exception of HSP90, they decreased over time. In conclusion, our study demonstrates that CKD progression is a complicated process that involves HSPs, but they do not predict CKD progression. The protective role of HSPs against CKD may weaken over time, and HSP90 may have a detrimental effect on the disease course.