Fatih Kocabas

Fatih Kocabas
Yeditepe University · Department of Genetics and Bioengineering

PhD

About

87
Publications
8,090
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Introduction
Fatih Kocabas currently works at the Department of Genetics and Bioengineering, Yeditepe University. Fatih does research in Cancer Research, Molecular Biology and Cell Biology. Their current project is 'Small Molecule Induced Ex Vivo Hematopoietic Stem Cell Expansion'.
Additional affiliations
August 2014 - present
Yeditepe University
Position
  • Professor (Assistant)

Publications

Publications (87)
Article
Hematopoietic stem cells (HSCs), which are multipotent and have the ability to self‐renew, are frequently used in the treatment of hematological diseases and cancer. Small molecules that target HSC quiescence regulators could be used for ex vivo expansion of both mobilized peripheral blood (mPB) and umbilical cord blood (UCB) hematopoietic stem and...
Article
Interleukin-2 (IL-2) and its receptor play a pivotal role in the regulation of immune response and possess both immune-regulatory and immune-stimulatory functions. As a cytokine of lymphoid cells, the role of IL-2 has been revealed in hematopoietic stem cell (HSC) maintenance and proper hematopoiesis. Here, we investigated that small molecule Ro 26...
Chapter
Acute leukemia (AL) is a poor progressive resistant hematological disease, which has different subtypes and immunophenotypic properties according to leukemic blasts. AL is caused by genetic changes and associated with leukemia stem cells (LSCs), which determine its prognosis and endurance. LSCs are thought to be hematopoietic progenitor and stem ce...
Article
Full-text available
Hematopoietic stem cell (HSCs) transplantation is the primary therapeutic modality used to treat hematopoietic disorders. It centers on the capability of a small quantity of HSCs to repopulate whole blood lineages. Along with limited availability of suitable donors, the need for sufficient number of donor HSCs is still challenging in clinical relev...
Article
Mesenchymal stem cells (MSCs) have been shown to be promising for regenerative medicines with their immunomodulatory characteristics. They may be obtained from a variety of tissue types, including umbilical cord, adipose tissue, dental tissue, and bone marrow (BM). BM-MSCs are challenging in terms of their ex vivo expansion capability. Thus, we aim...
Article
Hematopoietic stem cells (HSCs) are essential in the production and maintenance of red blood and immune cells. Small molecules that target HSC modulators may aid in the proliferation and expansion of HSCs. To that end, we investigated the effect of two small molecules on HSC expansion: pluripotin (an ERK1 and RasGAP inhibitor) and CHIR-99021 (a GSK...
Article
Full-text available
Neonatal mammalian heart has been shown to possess the capacity to regenerate substantially after an injury. This remarkable regenerative capacity is lost in a week. This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after myocardial infarction in adult hearts. Recent studi...
Article
Full-text available
OTU proteases antagonize the cellular defense in the host cells and involve in pathogenesis. Intriguingly, P. falciparum, P. vivax, and P. yoelii have an uncharacterized and highly conserved viral OTU-like proteins. However, their structure, function or inhibitors have not been previously reported. To this end, we have performed structural modeling...
Article
Endothelial cells (ECs) are essential in the growth and progression of the tumor cells by supplying nutrition and angiogenesis factors. Targeting ECs emerged as a major strategy to prevent the growth of tumors. Studies suggest that ERK1/2 signaling is important for endothelial cells, which could be specifically targeted by small molecule SC1. We ai...
Article
The current COVID-19 outbreak has had a profound influence on public health and daily life. Despite all restrictions and vaccination programs, COVID-19 still can lead to fatality due to a lack of COVID-19-specific treatments. A number of studies have demonstrated the feasibility to develop therapeutics by targeting underlying components of the vira...
Article
Hematopoietic stem cells (HSCs) are particularly characterized by their quiescence and self-renewal. Cell cycle regulators tightly control quiescence and self-renewal capacity. Studies suggest that modulation of ubiquitination and neddylation could contribute to HSC function via cyclin-dependent kinase inhibitors (CDKIs). S-phase kinase-associated...
Chapter
Gen terapisi, tarihsel olarak, insan hücrelerine yeni genlerin eklenmesi olarak tanımlanmıştır. Bununla birlikte, gen düzenleme teknolojilerinin ortaya çıkışı, insan genomunun belli bir dizisinin terapötik bir etki elde etmek için tam olarak manipüle edilebildiği yeni bir paradigmaya olanak sağlamıştır. Bu gelişim farklı mühendislik nükleazlarını k...
Chapter
The CRISPR/Cas9 is a RNA-guided nuclease complex that can be specifically programmed to target a user-specified DNA sequence. It has been a powerful and effective tool of genome editing. However, off-target activity of the Cas9 nuclease limits its potential use in the correction of inherited diseases and bona fide gene editing. Various protein engi...
Preprint
Full-text available
Hematopoietic stem cells (HSC), known for their ability to multipotent and self-renew, are often used in HSC transplantation for the treatment of hematological diseases and malignancies. Umbilical cord blood (UCB) and mobilized peripheral blood (mPB), which are alternatives to bone marrow (BM) for HSC transplantation, have reduced HSC. To address t...
Preprint
Full-text available
Hematopoietic stem/progenitor cell (HSPC) quiescence modulators play a key role in the modulation of HSPC numbers. Targeting HSPC modulators with small molecules could contribute to the cell cycle entry and expansion of HSPC. To this end, we have investigated the effect of two small molecules Pluripotin and CHIR-99021 on HSPC expansion. Both Plurip...
Article
Full-text available
The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease caused by Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) (Prec Clin Med 2020;3:9–13, Lancet 2020;395:497–506, N. Engl J Med 2020a;382:1199–207, Nature 2020;579:270–3). SARS-CoV-2 surveillance is essential to controlling widespread transmi...
Article
Full-text available
MEIS proteins are historically associated with tumorigenesis, metastasis, and invasion in cancer. MEIS and associated PBX-HOX proteins may act as tumor suppressors or oncogenes in different cellular settings. Their expressions tend to be misregulated in various cancers. Bioinformatic analyses have suggested their upregulation in leukemia/lymphoma,...
Article
ABSTACT Dermal fibroblasts are responsible from the production of extracellular matrix and take role in the closure of skin wounds. Dermal fibroblasts are major cell of origin in the generation of IPSCs and historically being used as feeder layer and biofiller in the restorative surgeries. Ex vivo expansion of the dermal fibroblasts provides a suit...
Article
Full-text available
Meis1, which belongs to TALE-type class of homeobox gene family, appeared as one of the key regulators of hematopoietic stem cell (HSC) self-renewal and a potential therapeutical target. However, small molecule inhibitors of MEIS1 remained unknown. This led us to develop inhibitors of MEIS1 that could modulate HSC activity. To this end, we have est...
Article
Hematopoietic stem cells (HSCs) are known to reside in a bone marrow (BM) niche, which is associated with relatively higher calcium content. HSCs sense and respond to calcium changes. However, how calcium‐sensing components modulate HSC function and expansion is largely unknown. We investigated temporal modulation of calcium sensing and Ca²⁺ homeos...
Article
Endothelial dysfunction is prominent in atherosclerosis, hypertension, diabetes, peripheral and cardiovascular diseases, and stroke. Novel therapeutic approaches to these conditions often involve development of tissue-engineered veins with ex vivo expanded endothelial cells. However, high cell number requirements limit these approaches to become ap...
Preprint
Full-text available
Meis1, which belongs to TALE-type class of homeobox gene family, appeared as one of the key regulators of hematopoietic stem cell (HSC) self-renewal and a potential therapeutical target. However, small molecule inhibitors of MEIS1 remained unknown. This led us to develop inhibitors of MEIS1 that could modulate HSC activity. To this end, we have est...
Article
Recent developments in gene editing technology have enabled scientists to modify DNA sequence by using engineered endonucleases. These gene editing tools are promising candidates for clinical applications, especially for treatment of inherited disorders like sickle cell disease (SCD). SCD is caused by a point mutation in human β-globin gene (HBB)....
Preprint
Full-text available
Recent developments in gene editing technology have enabled scientists to modify DNA sequence by using engineered endonucleases. These gene editing tools are promising candidates for clinical applications, especially for treatment of inherited disorders like sickle cell disease (SCD). SCD is caused by a point mutation in human β-globin gene (HBB)....
Chapter
Platelet and blood transfusions have vital importance to the lives of many patients. Platelet transfusions are a life-saving intervention by reducing risk of bleeding in thrombocytopenic patients. Due to the short shelf life of platelets and their limited availability, researchers have developed various platelet transfusion production technologies....
Preprint
Full-text available
c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Targeting modulators of HSC quiescence and metabolism could lead to HSC cell cycle entry with concomitant expansion. Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold increase in murine LSKCD34low HSC compartment pos...
Article
Background: c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Objective: Targeting modulators of HSC quiescence and metabolism could lead to HSC cell cycle entry with concomitant expansion. Methods and results: Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold...
Chapter
Full-text available
The common prevalence of heart failure and limitations in its treatment are leading cause of attention and interest towards the induction of cardiac regeneration with novel approaches. Recent studies provide growing evidence regarding bona fide cardiac regeneration post genetic manipulations, administration of stimulatory factors and myocardial inj...
Chapter
Hematopoietic stem cells (HSCs) are rare cells, which housed in the adult bone marrow. They maintain all types of differentiated blood cells throughout life. Due to limited availability of HSCs for transplantation, treatment of various inherited bone marrow disorders and anemia requires the development of HSC expansion and gene editing technologies...
Article
Background: Meis1 is a member of three-amino-acid loop extension (TALE) homeodomain transcription factors. Studies in the last decade have shown that Meis1 has crucial roles in cardiac regeneration, stem cell function, and tumorigenesis. Objective: We have recently demonstrated that knocking out of Meis1 in adult cardiomyocytes resulted in the i...
Conference Paper
Erişkin ve ya çocuklarda malign hastalıklar ya da doğuştan kazanılmış malign olmayan birçok hastalıkta hücrelerin yeniden yapılandırılmasını sağlamak adına kök hücre transplantasyonları tercih edilse de henüz klinik anlamda etkin bir biçimde transplantasyon için istenilen hücre büyümesi oranlarına ulaşılamamıştır. in vivo fazındaki hematopoetik kök...
Article
Full-text available
Heart has long been considered a terminally differentiated organ. Recent studies, however, have suggested that there is a modest degree of cardiomyocyte (CM) turnover in adult mammalian heart, albeit not sufficient for replacement of lost CMs following cardiac injuries. Cardiac regeneration studies in various model organisms including zebrafish, ne...
Article
Full-text available
Heart has long been considered a terminally differentiated organ. Recent studies, however, have suggested that there is a modest degree of cardiomyocyte (CM) turnover in adult mammalian heart, albeit not sufficient for replacement of lost CMs following cardiac injuries. Cardiac regeneration studies in various model organisms including zebrafish, ne...
Presentation
Hematopoetik kök hücrelerin (HKH) çoğaltılması, kök hücre alanındaki çalışmalarda karşılaşılan en önemli problemlerin başında gelmektedir. Birçok çalışmada bu problemi aşmak için HKH’lerin çoğaltılması sırasında büyüme faktörleri ve sitokinler kullanılmış ve hücrelerin durağan fazı (dormansi) hedeflenerek hücre döngüsü inhibitörleri ve inhibitör fa...
Conference Paper
We have previously showed that targeting HSC quiescence regulators not only lead to cell cycle entry but also induce HSC expansion . Intriguingly, an oncogene, c-myc, opposed to what has been expected following loss of function in bone marrow leads to accumulation of HSPCs upto 4 fold in vivo. Thus, transient inhibition of c-myc could provide a mea...
Presentation
Hematopoietic stem cells (HSC) and cardiomyocytes divide rarely and only after a stimulus. Identifying the function of Ub-activating E1 family and how they are involved in mitotic and endoreduplicative cell cycle progression may help to understand the mechanism of HSC quiescence [1,2,3] as well as post-natal cardiomyocyte cell cycle arrest [4,5,6]....
Poster
We have previously showed that targeting HSC quiescence regulators not only lead to cell cycle entry but also induce HSC expansion [1-3]. Intriguingly, an oncogene, c-myc, opposed to what has been expected following loss of function in bone marrow leads to accumulation of HSPCs upto 4 fold in vivo [4]. Thus, transient inhibition of c-myc could prov...
Conference Paper
Introduction & Aim Clinical therapies of stem cells have become a conspicuous research field especially with the fact of them being needed for autoimmune diseases and tissue transplantations for local immune repression. Recent studies show that stem cells carry high capacity of immunomodulation [1,2,3]. Despite human adipogenic stem cells (hASCs) w...
Conference Paper
Mesenchymal stem cells (MSCs) and their clinical therapies have turned into a gold studying field recently.Regarding to the immunomodulatory effects, MSCs carry a significant potential for preventing tissue incompatibility.Nowadays, scientists established that, human newborn foreskin stem cells carry hematopoietic stem cell surface markers.These de...
Conference Paper
Full-text available
Crimean-Congo hemorrhagic fever virus (CCHFV) is a deadly tick born virus with no currently existing therapies. In the L segment of CCHFV genome, CHFV OTU deubiquitinase is expressed and involve in viral invasion through antagonizing of NF-κB signaling pathway. Development of robust drug screening strategies and identification of small molecule inh...
Article
Full-text available
Findings in the last decade suggest that there is a considerable amount of cardiomyocyte turnover in the human heart throughout life, albeit not sufficient for heart regeneration following myocardial infarctions. Only a few species are known to be remarkably efficient in cardiac regeneration. They restore lost cardiomyocytes via a process of cardio...
Article
Full-text available
Crimean-Congo hemorrhagic fever virus (CCHFV) is a deadly tick-borne virus with high mortality rates. Current antivirals lack specificity, making them susceptible to off-target effects and cytotoxicity. There is an outmost need for the identification of active compounds for anti-CCHFV therapies. Inhibition of CCHFV OTU protease by small molecules i...
Article
Full-text available
Hematopoietic stem cells (HSC) are primarily dormant but have the potential to become highly active on demand to reconstitute blood. This requires a swift metabolic switch from glycolysis to mitochondrial oxidative phosphorylation. Maintenance of low levels of reactive oxygen species (ROS), a by-product of mitochondrial metabolism, is also necessar...
Article
Full-text available
Crimean-Congo hemorrhagic fever virus (CCHFV) is a deadly virus that has been listed in the Category C as a potential bioterror agent. There are no specific therapies against CCHFV, which urges identification of potential therapeutic targets and development of CCHFV therapies. CCHFV OTU protease takes an important role in viral invasion through ant...
Article
Full-text available
Adult hematopoietic stem cells (HSCs) are maintained in a microenvironment, known as niche in the endosteal regions of the bone marrow. This stem cell niche with low oxygen tension requires HSCs to adopt a unique metabolic profile. We have recently demonstrated that mouse long-term hematopoietic stem cells (LT-HSCs) utilize glycolysis instead of mi...
Article
Full-text available
There is an outmost need for the identification of specific antiviral compounds. Current antivirals lack specificity, making them susceptible to off-target effects, and highlighting importance of development of assays to discover antivirals targeting viral specific proteins. Previous studies for identification of inhibitors of RNA-dependent RNA pol...
Article
Full-text available
An important feature of stem cells is their maintenance in their respective hypoxic niche. Survival in this low-oxygen microenvironment requires significant metabolic adaptation. We demonstrated that mouse HSCs utilize glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands. We have adapted various tools for chara...
Article
Full-text available
How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch f...