About
We aim to demonstrate that increased activity of neural stem cells (induced plasticity)…
Contributions
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Here's how you can create a network of support to navigate failure in your R&D career.
While developing a mindset that views setbacks as opportunities for growth is essential, emphasizing the importance of embracing the discomfort that comes with challenges is as well. The phrase "no pain, no gain" encapsulates the reality that significant progress often requires enduring difficult and uncomfortable experiences. Focusing solely on mental and emotional well-being practices like mindfulness might give the impression that resilience is solely about maintaining balance. In reality, true resilience is built through facing and overcoming adversity head-on, learning to thrive under pressure, and using each challenging experience as a stepping stone for future success.
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Here's how you can create a network of support to navigate failure in your R&D career.
One thing I've found helpful in fostering personal resilience is embracing the challenges and setbacks as integral parts of the learning process. This allows to develop a stronger, more resilient approach. By viewing difficulties as opportunities to grow and improve, one may maintain motivation and drive even in the face of significant obstacles. This perspective not only enhances personal resilience but also promotes a culture of perseverance and innovation within the team.
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Here's how you can create a network of support to navigate failure in your R&D career.
While I appreciate the emphasis on seeking out colleagues who understand the unique challenges of R&D, I believe there should be a stronger focus on interdisciplinary collaboration. Limiting our peer circle to those within the same field might restrict the diversity of perspectives that can lead to truly innovative solutions. Including peers from different disciplines can offer fresh insights and creative approaches to problem-solving, which is essential in R&D. Additionally, more structured mentorship programs could be beneficial, as they provide guidance from experienced professionals who can offer strategic advice and support beyond peer interactions.
Activity
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Please check out our latest work. Using 12 hiPSC lines and our newly developed spinal cord differentiation protocol, we created thousands of spinal…
Please check out our latest work. Using 12 hiPSC lines and our newly developed spinal cord differentiation protocol, we created thousands of spinal…
Liked by Caghan Kizil
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Happy to share our latest paper just published in Cell Reports Medicine, where we have discovered fate commitment defects of neuromesodermal…
Happy to share our latest paper just published in Cell Reports Medicine, where we have discovered fate commitment defects of neuromesodermal…
Liked by Caghan Kizil
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Groundbreaking research! Researchers at MUSC Hollings Cancer Center have developed a new compound that shows promise in overcoming chemotherapy…
Groundbreaking research! Researchers at MUSC Hollings Cancer Center have developed a new compound that shows promise in overcoming chemotherapy…
Liked by Caghan Kizil
Experience
Education
Licenses & Certifications
Publications
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Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain
PLOS Biology
It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models in which the molecular basis of disease-induced neuronal regeneration could be investigated. We previously found that zebrafish stimulates neural stem cell (NSC) plasticity and neurogenesis in AD and could help to understand the mechanisms to be harnessed for developing new neurons in diseased mammalian brains. Here,…
It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models in which the molecular basis of disease-induced neuronal regeneration could be investigated. We previously found that zebrafish stimulates neural stem cell (NSC) plasticity and neurogenesis in AD and could help to understand the mechanisms to be harnessed for developing new neurons in diseased mammalian brains. Here, by performing single-cell transcriptomics, we found that amyloid toxicity-induced interleukin-4 (IL4) promotes NSC proliferation and neurogenesis by suppressing the tryptophan metabolism and reducing the production of serotonin. NSC proliferation was suppressed by serotonin via down-regulation of brain-derived neurotrophic factor (BDNF)-expression in serotonin-responsive periventricular neurons. BDNF enhances NSC plasticity and neurogenesis via nerve growth factor receptor A (NGFRA)/ nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFkB) signaling in zebrafish but not in rodents. Collectively, our results suggest a complex neuron-glia interaction that regulates regenerative neurogenesis after AD conditions in zebrafish.
Other authorsSee publication -
Alzheimer's disease, neural stem cells and neurogenesis: cellular phase at single-cell level
Neural Regeneration Research
Alzheimer's disease cannot be cured as of yet. Our current understanding on the causes of Alzheimer's disease is limited. To develop treatments, experimental models that represent a particular cellular phase of the disease and more rigorous scrutiny of the cellular pathological mechanisms are crucial. In recent years, Alzheimer's disease research underwent a paradigm shift. According to this tendency, Alzheimer's disease is increasingly being conceived of a disease where not only neurons but…
Alzheimer's disease cannot be cured as of yet. Our current understanding on the causes of Alzheimer's disease is limited. To develop treatments, experimental models that represent a particular cellular phase of the disease and more rigorous scrutiny of the cellular pathological mechanisms are crucial. In recent years, Alzheimer's disease research underwent a paradigm shift. According to this tendency, Alzheimer's disease is increasingly being conceived of a disease where not only neurons but also multiple cell types synchronously partake to manifest the pathology. Knowledge on every cell type adds an alternative approach and hope for the efforts towards the treatment. Neural stem cells and their neurogenic ability are making an appearance as a new aspect of the disease manifestation based on the recent findings that neurogenesis reduces dramatically in Alzheimer's disease patients compared to healthy individuals. Therefore, understanding how neural stem cells can form new neurons in Alzheimer's disease brains holds an immense potential for clinics. However, this provocative idea requires further evidence and tools for investigation. Recently, single cell sequencing appeared as a revolutionary tool to understand cellular programs in unprecedented resolution and it will undoubtedly facilitate comprehensive investigation of different cell types in Alzheimer's disease. In this mini-review, we will touch upon recent studies that use single cell sequencing for investigating cellular response in Alzheimer's disease and some consideration pertaining to the utilization of neural regeneration for Alzheimer's disease research.
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Glia-neuron interactions underlie state transitions to generalized seizures.
Nature Communications
Brain activity and connectivity alter drastically during epileptic seizures. The brain networks shift from a balanced resting state to a hyperactive and hypersynchronous state. It is, however, less clear which mechanisms underlie the state transitions. By studying neural and glial activity in zebrafish models of epileptic seizures, we observe striking differences between these networks. During the preictal period, neurons display a small increase in synchronous activity only locally, while the…
Brain activity and connectivity alter drastically during epileptic seizures. The brain networks shift from a balanced resting state to a hyperactive and hypersynchronous state. It is, however, less clear which mechanisms underlie the state transitions. By studying neural and glial activity in zebrafish models of epileptic seizures, we observe striking differences between these networks. During the preictal period, neurons display a small increase in synchronous activity only locally, while the gap-junction-coupled glial network was highly active and strongly synchronized across large distances. The transition from a preictal state to a generalized seizure leads to an abrupt increase in neural activity and connectivity, which is accompanied by a strong alteration in glia-neuron interactions and a massive increase in extracellular glutamate. Optogenetic activation of glia excites nearby neurons through the action of glutamate and gap junctions, emphasizing a potential role for glia-glia and glia-neuron connections in the generation of epileptic seizures.
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Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity
Cell Reports
The neural stem cell (NSC) reservoir can be harnessed for stem cell-based regenerative therapies. Zebrafish remarkably regenerate their brain by inducing NSC plasticity in a Amyloid-β-42 (Aβ42)-induced experimental Alzheimer's disease (AD) model. Interleukin-4 (IL-4) is also critical for AD-induced NSC proliferation. However, the mechanisms of this response have remained unknown. Using single-cell transcriptomics in the adult zebrafish brain, we identify distinct subtypes of NSCs and neurons…
The neural stem cell (NSC) reservoir can be harnessed for stem cell-based regenerative therapies. Zebrafish remarkably regenerate their brain by inducing NSC plasticity in a Amyloid-β-42 (Aβ42)-induced experimental Alzheimer's disease (AD) model. Interleukin-4 (IL-4) is also critical for AD-induced NSC proliferation. However, the mechanisms of this response have remained unknown. Using single-cell transcriptomics in the adult zebrafish brain, we identify distinct subtypes of NSCs and neurons and differentially regulated pathways and their gene ontologies and investigate how cell-cell communication is altered through ligand-receptor pairs in AD conditions. Our results propose the existence of heterogeneous and spatially organized stem cell populations that react distinctly to amyloid toxicity. This resource article provides an extensive database for the molecular basis of NSC plasticity in the AD model of the adult zebrafish brain. Further analyses of stem cell heterogeneity and neuro-regenerative ability at single-cell resolution could yield drug targets for mobilizing NSCs for endogenous neuro-regeneration in humans.
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Dual Inhibition of GSK3β and CDK5 Protects the Cytoskeleton of Neurons from Neuroinflammatory-Mediated Degeneration In Vitro and In Vivo.
Stem Cell Reports
Neuroinflammation is a hallmark of neurological disorders and is accompanied by the production of neurotoxic agents such as nitric oxide. We used stem cell-based phenotypic screening and identified small molecules that directly protected neurons from neuroinflammation-induced degeneration. We demonstrate that inhibition of CDK5 is involved in, but not sufficient for, neuroprotection. Instead, additional inhibition of GSK3β is required to enhance the neuroprotective effects of CDK5 inhibition…
Neuroinflammation is a hallmark of neurological disorders and is accompanied by the production of neurotoxic agents such as nitric oxide. We used stem cell-based phenotypic screening and identified small molecules that directly protected neurons from neuroinflammation-induced degeneration. We demonstrate that inhibition of CDK5 is involved in, but not sufficient for, neuroprotection. Instead, additional inhibition of GSK3β is required to enhance the neuroprotective effects of CDK5 inhibition, which was confirmed using short hairpin RNA-mediated knockdown of CDK5 and GSK3β. Quantitative phosphoproteomics and high-content imaging demonstrate that neurite degeneration is mediated by aberrant phosphorylation of multiple microtubule-associated proteins. Finally, we show that our hit compound protects neurons in vivo in zebrafish models of motor neuron degeneration and Alzheimer's disease. Thus, we demonstrate an overlap of CDK5 and GSK3β in mediating the regulation of the neuronal cytoskeleton and that our hit compound LDC8 represents a promising starting point for neuroprotective drugs.
Other authorsSee publication -
GATA3 Promotes the Neural Progenitor State but Not Neurogenesis in 3D Traumatic Injury Model of Primary Human Cortical Astrocytes
Frontiers in Cellular Neuroscience
Astrocytes are abundant cell types in the vertebrate central nervous system and can act as neural stem cells in specialized niches where they constitutively generate new neurons. Outside the stem cell niches, however, these glial cells are not neurogenic. Although injuries in the mammalian central nervous system lead to profound proliferation of astrocytes, which cluster at the lesion site to form a gliotic scar, neurogenesis does not take place. Therefore, a plausible regenerative therapeutic…
Astrocytes are abundant cell types in the vertebrate central nervous system and can act as neural stem cells in specialized niches where they constitutively generate new neurons. Outside the stem cell niches, however, these glial cells are not neurogenic. Although injuries in the mammalian central nervous system lead to profound proliferation of astrocytes, which cluster at the lesion site to form a gliotic scar, neurogenesis does not take place. Therefore, a plausible regenerative therapeutic option is to coax the endogenous reactive astrocytes to a pre-neurogenic progenitor state and use them as an endogenous reservoir for repair. However, little is known on the mechanisms that promote the neural progenitor state after injuries in humans. Gata3 was previously found to be a mechanism that zebrafish brain uses to injury-dependent induction of neural progenitors. However, the effects of GATA3 in human astrocytes after injury are not known. Therefore, in this report, we investigated how overexpression of GATA3 in primary human astrocytes would affect the neurogenic potential before and after injury in 2D and 3D cultures. We found that primary human astrocytes are unable to induce GATA3 after injury. Lentivirus-mediated overexpression of GATA3 significantly increased the number of GFAP/SOX2 double positive astrocytes and expression of pro-neural factor ASCL1, but failed to induce neurogenesis, suggesting that GATA3 is required for enhancing the neurogenic potential of primary human astrocytes and is not sufficient to induce neurogenesis alone.
Other authorsSee publication -
Is Alzheimer's Also a Stem Cell Disease? - The Zebrafish Perspective.
Frontiers in Cell and Developmental Biology
Alzheimer’s disease (AD) is the most common neurodegenerative disease and is the leading form of dementia. AD entails chronic inflammation, impaired synaptic integrity and reduced neurogenesis. The clinical and molecular onsets of the disease do not temporally overlap and the initiation phase of the cellular changes might start with a complex causativeness between chronic inflammation, reduced neural stem cell plasticity and neurogenesis. Although the immune and neuronal aspects in AD are well…
Alzheimer’s disease (AD) is the most common neurodegenerative disease and is the leading form of dementia. AD entails chronic inflammation, impaired synaptic integrity and reduced neurogenesis. The clinical and molecular onsets of the disease do not temporally overlap and the initiation phase of the cellular changes might start with a complex causativeness between chronic inflammation, reduced neural stem cell plasticity and neurogenesis. Although the immune and neuronal aspects in AD are well studied, the neural stem cell-related features are far less investigated. An intriguing question is, therefore, whether a stem cell can ever be made proliferative and neurogenic during the prevalent AD in the brain. Recent findings affirm this hypothesis and thus a plausible way to circumvent the AD phenotypes could be to mobilize the endogenous stem cells by enhancing their proliferative and neurogenic capacity as well as to provide the newborn neurons the potential to survive and integrate into the existing circuitry. To address these questions, zebrafish offers unprecedented information and tools, which can be effectively translated into mammalian experimental systems.
Other authorsSee publication -
3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues Aβ42-Induced Loss of Human Neural Stem Cell Plasticity.
Developmental Cell
Neural stem cells (NSCs) constitute an endogenous reservoir for neurons that could potentially be harnessed for regenerative therapies in disease contexts such as neurodegeneration. However, in Alzheimer's disease (AD), NSCs lose plasticity and thus possible regenerative capacity. We investigate how NSCs lose their plasticity in AD by using starPEG-heparin-based hydrogels to establish a reductionist 3D cell-instructive neuro-microenvironment that promotes the proliferative and neurogenic…
Neural stem cells (NSCs) constitute an endogenous reservoir for neurons that could potentially be harnessed for regenerative therapies in disease contexts such as neurodegeneration. However, in Alzheimer's disease (AD), NSCs lose plasticity and thus possible regenerative capacity. We investigate how NSCs lose their plasticity in AD by using starPEG-heparin-based hydrogels to establish a reductionist 3D cell-instructive neuro-microenvironment that promotes the proliferative and neurogenic ability of primary and induced human NSCs. We find that administration of AD-associated Amyloid-β42 causes classical neuropathology and hampers NSC plasticity by inducing kynurenic acid (KYNA) production. Interleukin-4 restores NSC proliferative and neurogenic ability by suppressing the KYNA-producing enzyme Kynurenine aminotransferase (KAT2), which is upregulated in APP/PS1dE9 mouse model of AD and in postmortem human AD brains. Thus, our culture system enables a reductionist investigation of regulation of human NSC plasticity for the identification of potential therapeutic targets for intervention in AD.
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Human TAUP301L overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain
Nature Publishing Group / Scientific Reports
Alzheimer's disease is the most common neurodegenerative disease, and one of the cellular hallmarks is toxicity caused by a protein called TAU. In humans, mutations in TAU leads to disruption of the microtubules, the major transport routes in our neurons. When we lose the integrity of our microtubules, neurons die. A big question is: "Can we stop the death of neurons by preventing the toxicity of TAU protein, and can we cure neurodegeneration?"
We are excited to have a clue that…Alzheimer's disease is the most common neurodegenerative disease, and one of the cellular hallmarks is toxicity caused by a protein called TAU. In humans, mutations in TAU leads to disruption of the microtubules, the major transport routes in our neurons. When we lose the integrity of our microtubules, neurons die. A big question is: "Can we stop the death of neurons by preventing the toxicity of TAU protein, and can we cure neurodegeneration?"
We are excited to have a clue that zebrafish may show us the way how to prevent TAU-dependent neurodegenerative disorders such as Alzheimer's disease or Frontotemporal Dementia. In our study, we made the zebrafish brain produce the most aggressive and disease-associated mutated version of human TAU protein. As a result, we found that zebrafish brain may have a molecular program that prevents TAU-mediated toxicity, and keeps the neurons alive. This finding is significant and may help us to find out how we can cure TAU-dependent neurodegenerative diseases in humans.Other authorsSee publication -
Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain
Journal of Visualized Experiments
This protocol describes the synthesis, characterization, and injection of monomeric amyloid-β42 peptides for generating amyloid toxicity in adult zebrafish to establish an Alzheimer's disease model, followed by histological analyses and detection of aggregations.
Other authorsSee publication -
The effects of aging on Amyloid-β42-induced neurodegeneration and regeneration in adult zebrafish brain
Neurogenesis
Alzheimer disease is the most prevalent neurodegenerative disease and is associated with aggregation of Amyloid-β42 peptides. In mammals, Amyloid-β42 causes impaired neural stem/progenitor cell (NSPC) proliferation and neurogenesis, which exacerbate with aging. The molecular programs necessary to enhance NSPC proliferation and neurogenesis in our brains to mount successful regeneration are largely unknown. Therefore, to identify the molecular basis of effective brain regeneration, we previously…
Alzheimer disease is the most prevalent neurodegenerative disease and is associated with aggregation of Amyloid-β42 peptides. In mammals, Amyloid-β42 causes impaired neural stem/progenitor cell (NSPC) proliferation and neurogenesis, which exacerbate with aging. The molecular programs necessary to enhance NSPC proliferation and neurogenesis in our brains to mount successful regeneration are largely unknown. Therefore, to identify the molecular basis of effective brain regeneration, we previously established an Amyloid-β42 model in adult zebrafish that displayed Alzheimer-like phenotypes reminiscent of humans. Interestingly, zebrafish exhibited enhanced NSPC proliferation and neurogenesis after microinjection of Amyloid-β42 peptide. Here, we compare old and young fish to address the effects of aging on regenerative ability after Amyloid-β42 deposition. We found that aging does not affect the rate of NSPC proliferation but reduces the neurogenic response and microglia/macrophage activation after microinjection of Amyloid-β42 in zebrafish, suggesting an important link between aging, neuroinflammation, regenerative neurogenesis and neural stem cell plasticity.
Other authorsSee publication -
IL4/STAT6 Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain
Cell Reports
We generated an Amyloid-β42 toxicity model in adult zebrafish brain, which shows cell death, microglial activation, synaptic degeneration and learning deficits. Unlike humans, fish brain increase stem cell proliferation and neurogenesis upon Aβ42. We found that Interleukin-4 as a key mediator of this response via a neuro-immune crosstalk. This report in Cell Reports shows for the first time that IL4 has such a direct effect on neural stem cells.
Other authorsSee publication -
Neural stem/progenitor cells in Alzheimer’s disease
Yale Journal of Biology and Medicine
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and a worldwide health challenge. Different therapeutic approaches are being developed to reverse or slow the loss of affected neurons. Another plausible therapeutic way that may complement the studies is to increase the survival of existing neurons by mobilizing the existing neural stem/progenitor cells (NSPCs) — i.e. “induce their plasticity” — to regenerate lost neurons despite the existing pathology and unfavorable…
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and a worldwide health challenge. Different therapeutic approaches are being developed to reverse or slow the loss of affected neurons. Another plausible therapeutic way that may complement the studies is to increase the survival of existing neurons by mobilizing the existing neural stem/progenitor cells (NSPCs) — i.e. “induce their plasticity” — to regenerate lost neurons despite the existing pathology and unfavorable environment. However, there is controversy about how NSPCs are affected by the unfavorable toxic environment during AD. In this review, we will discuss the use of stem cells in neurodegenerative diseases and in particular how NSPCs affect the AD pathology and how neurodegeneration affects NSPCs. In the end of this review, we will discuss how zebrafish as a useful model organism with extensive regenerative ability in the brain might help to address the molecular programs needed for NSPCs to respond to neurodegeneration by enhanced neurogenesis.
Other authorsSee publication -
Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides
PLoS One
Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected…
Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two– polyR and Trans – that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael’s addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.
Other authorsSee publication -
Effects of inflammation on stem cells: together they strive?
EMBO Reports
Inflammation entails a complex set of defense mechanisms acting in concert to restore the homeostatic balance in organisms after damage or pathogen invasion. This immune response consists of the activity of various immune cells in a highly complex manner. Inflammation is a double‐edged sword as it is reported to have both detrimental and beneficial consequences. In this review, we discuss the effects of inflammation on stem cell activity, focusing primarily on neural stem/progenitor cells in…
Inflammation entails a complex set of defense mechanisms acting in concert to restore the homeostatic balance in organisms after damage or pathogen invasion. This immune response consists of the activity of various immune cells in a highly complex manner. Inflammation is a double‐edged sword as it is reported to have both detrimental and beneficial consequences. In this review, we discuss the effects of inflammation on stem cell activity, focusing primarily on neural stem/progenitor cells in mammals and zebrafish. We also give a brief overview of the effects of inflammation on other stem cell compartments, exemplifying the positive and negative role of inflammation on stemness. The majority of the chronic diseases involve an unremitting phase of inflammation due to improper resolution of the initial pro‐inflammatory response that impinges on the stem cell behavior. Thus, understanding the mechanisms of crosstalk between the inflammatory milieu and tissue‐resident stem cells is an important basis for clinical efforts. Not only is it important to understand the effect of inflammation on stem cell activity for further defining the etiology of the diseases, but also better mechanistic understanding is essential to design regenerative therapies that aim at micromanipulating the inflammatory milieu to offset the negative effects and maximize the beneficial outcomes.
Other authorsSee publication -
Regeneration, Plasticity, and Induced Molecular Programs in Adult Zebrafish Brain
BioMed Research International
Regenerative capacity of the brain is a variable trait within animals. Aquatic vertebrates such as zebrafish have widespread ability to renew their brains upon damage, while mammals have—if not none—very limited overall regenerative competence. Underlying cause of such a disparity is not fully evident; however, one of the reasons could be activation of peculiar molecular programs, which might have specific roles after injury or damage, by the organisms that regenerate. If this hypothesis is…
Regenerative capacity of the brain is a variable trait within animals. Aquatic vertebrates such as zebrafish have widespread ability to renew their brains upon damage, while mammals have—if not none—very limited overall regenerative competence. Underlying cause of such a disparity is not fully evident; however, one of the reasons could be activation of peculiar molecular programs, which might have specific roles after injury or damage, by the organisms that regenerate. If this hypothesis is correct, then there must be genes and pathways that (a) are expressed only after injury or damage in tissues, (b) are biologically and functionally relevant to restoration of neural tissue, and (c) are not detected in regenerating organisms. Presence of such programs might circumvent the initial detrimental effects of the damage and subsequently set up the stage for tissue redevelopment to take place by modulating the plasticity of the neural stem/progenitor cells. Additionally, if transferable, those “molecular mechanisms of regeneration” could open up new avenues for regenerative therapies of humans in clinical settings. This review focuses on the recent studies addressing injury/damage-induced molecular programs in zebrafish brain, underscoring the possibility of the presence of genes that could be used as biomarkers of neural plasticity and regeneration.
Other authorsSee publication -
Simplet/Fam53b is required for Wnt signal transduction by regulating β-catenin nuclear localization.
Development
Kizil C, Küchler B, Yan JJ, Ozhan G, Moro E, Argenton F, Brand M, Weidinger G,
Antos CL. Development. 141(18):3529-39. doi:10.1242/dev.108415Other authorsSee publication -
Neuroinflammation and central nervous system regeneration in vertebrates
Trends in Cell Biology
Injuries in the central nervous system (CNS) are one of the leading causes of mortality or persistent disabilities in humans. One of the reasons why humans cannot recover from neuronal loss is the limited regenerative capacity of their CNS. By contrast, non-mammalian vertebrates exhibit widespread regeneration in diverse tissues including the CNS. Understanding those mechanisms activated during regeneration may improve the regenerative outcome in the severed mammalian CNS. Of those mechanisms…
Injuries in the central nervous system (CNS) are one of the leading causes of mortality or persistent disabilities in humans. One of the reasons why humans cannot recover from neuronal loss is the limited regenerative capacity of their CNS. By contrast, non-mammalian vertebrates exhibit widespread regeneration in diverse tissues including the CNS. Understanding those mechanisms activated during regeneration may improve the regenerative outcome in the severed mammalian CNS. Of those mechanisms, recent evidence suggests that inflammation may be important in regeneration. In this review we compare the different events following acute CNS injury in mammals and non-mammalian vertebrates. We also discuss the involvement of the immune response in initiating regenerative programs and how immune cells and neural stem/progenitor cells (NSPCs) communicate.
Other authorsSee publication -
Turkey must end violent response to protests
Science
Altindis E, Alpar MA, Aksay E, Beckwith J, Bökel C, Curl RF, Darnell RB, Elledge SJ, Erman B, Frahm J, Goff SP, Greengard P, Hoffmann R, Ilhan B, Kaslin J, Lipkin SM, Poulopoulou C, Raz E, Rubin MA, Salturk M, Schrock RR, Trautmann A, Unutmaz D, Weinstein H, Kizil C.
doi: 10.1126/science.341.6143.236-aOther authorsSee publication -
Micromanipulation of gene expression in the adult zebrafish brain using cerebroventricular microinjection of morpholino oligonucleotides.
The Journal of Visualized Experiments (JoVE)
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Regenerative Neurogenesis from Neural Progenitor Cells Requires Injury-Induced Expression of Gata3
Developmental Cell
Kizil C, Kyritsis N, Dudczig S, Kroehne V, Freudenreich D, Kaslin J, Brand M.
doi:10.1016/j.devcel.2012.10.014.Other authorsSee publication -
Acute inflammation initiates the regenerative response in the adult zebrafish brain.
Science
Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche
A, Brand M.
doi:10.1126/science.1228773.Other authorsSee publication -
The chemokine receptor cxcr5 regulates the regenerative neurogenesis response in the adult zebrafish brain.
Neural Development
Kizil C, Dudczig S, Kyritsis N, Machate A, Blaesche J, Kroehne V, Brand M.
doi: 10.1186/1749-8104-7-27.
Other authorsSee publication -
Adult neurogenesis and brain regeneration in zebrafish.
Developmental Neurobiology
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Academic autonomy: more freedom for Turkish science
Nature
Kizil C.
doi: 10.1038/477538d. -
Cerebroventricular microinjection (CVMI) into adult zebrafish brain is an efficient misexpression method for forebrain ventricular cells.
PLoS ONE
Kizil C, Brand M.
doi: 10.1371/journal.pone.0027395.
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Characterization of fam53b, simplet (smp) gene in caudal fin regeneration and embryonic development of zebrafish (Danio rerio)
Eberhard-Karls Universitaet Tubingen / Max Planck Institute for Developmental Biology
Dissertation Thesis
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Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration.
Developmental Biology
Kizil C, Otto GW, Geisler R, Nüsslein-Volhard C, Antos CL.
doi:10.1016/j.ydbio.2008.09.032.Other authorsSee publication -
Charcterization of sox11A gene expression during larval development and regeneration and promotor analysis during development of zebrafish (Danio rerio)
Georg-August University of Gottingen / MAx Planck Institute for Developmental Biology
Master's Thesis.
Patents
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METHOD FOR FORMING A FUNCTIONAL NETWORK OF HUMAN NEURONAL AND GLIAL CELLS
Issued DE PCT/DE2017/100408
Honors & Awards
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Schaefer Research Scholars Award for Excellence in Human Physiology Research
Columbia University
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European Union Regional Development Funds R&D Technology Development
European Union / SAB
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Helmholtz Validation Funds
Helmholtz Association
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Permanent W2 position
DZNE, Helmholtz Association
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Research grant
Deutsche Forschungsgemeinschaft
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Research Grant
Deutsche Forschungsgemeinschaft (DFG)
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Innovation-to-Application (I2A) Award
DZNE, Helmholtz Association
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Research Grant
Deutsche Forschungsgemeinschaft (DFG)
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Helmholtz Young Investigator Award
Helmholtz Association, Germany
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Associate Professorship
YÖK, Turkey
- Universitelerarasi Kurul, Turkey - Associate Professorship (Turkey)
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Research Award
Alzheimer Research Initiative e.V.
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Travel Award
The Company of Biologists, Oxford University Press, UK
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Meeting Scholarship (Keystone)
National Institute fo Health, USA
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Travel Award
International Society for Stem Cell Research (ISSCR), USA
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Travel Award
Gordon Research Conferences, USA
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Research Fellowship
TU Dresden
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Research scholarship
Max Planck Society, Germany
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Research Fellowship
Max Planck Society, Germany
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Basic science research scholarship
TÜBITAK, Turkey
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Scholarship
Roketsan AS, Turkey
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Distinction award
Ministry of Education, Turkey
- Mimistry of Education fellowship for undergraduate studies abroad (1999) (Turkey)
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Qualification
Ministry of Education, Turkey
- 53rd place in University Entrance Exams (1999) (Turkey)
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Science scholarship
Middle East Technical University, Turkey
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Success award
Turkiye Is Bankasi, Turkey
- Türkiye Is Bankasi A.S University Entrance Exams Success Award (1999). (Turkey)
Languages
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English
Native or bilingual proficiency
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Turkish
Native or bilingual proficiency
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German
Professional working proficiency
Organizations
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New York Academy of Sciences
Professional Member
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German Stem Cell Network
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- Present -
Society for Neuroscience (SfN)
Member
- Present -
The European Society for Fish Models in Biology and Medicine (EuFishBioMed)
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- Present -
International Society of Stem Cell Research (ISSCR)
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Federation of European Neuroscience Societies (FENS)
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German Society for Developmental Biology (GfE)
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More activity by Caghan
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Excited that today in Nature our collaboration with Manolis Kellis and David Bennett has published an analysis of scRNAseq data from more than 1.3…
Excited that today in Nature our collaboration with Manolis Kellis and David Bennett has published an analysis of scRNAseq data from more than 1.3…
Liked by Caghan Kizil
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Happy to see that our paper on new lysyl oxidase inhibitors in overcoming chemoresistance in TNBC is out today! I thank my lab members Metin Cetin…
Happy to see that our paper on new lysyl oxidase inhibitors in overcoming chemoresistance in TNBC is out today! I thank my lab members Metin Cetin…
Liked by Caghan Kizil
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Join us at Columbia University Irving Medical Center! 🌟 🐟 🔬 We are hiring a Technician B to support our research in New York City. This role…
Join us at Columbia University Irving Medical Center! 🌟 🐟 🔬 We are hiring a Technician B to support our research in New York City. This role…
Shared by Caghan Kizil
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Big thanks to Kurt von Figura and Andrej Hasilik. 40 years ago, you changed the direction of my life…” (the missing ’T’ was a price worth paying 😉)…
Big thanks to Kurt von Figura and Andrej Hasilik. 40 years ago, you changed the direction of my life…” (the missing ’T’ was a price worth paying 😉)…
Liked by Caghan Kizil
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As part of the new Department of Life Sciences initiative at the University of Bath, we are recruiting to sixpositions in the broad field of…
As part of the new Department of Life Sciences initiative at the University of Bath, we are recruiting to sixpositions in the broad field of…
Liked by Caghan Kizil
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Konstantinos Lazaridis and I spoke with NPR Cathy Wurzer about the #exposome and #exposomics for new podcast from the Mayo Clinic. Cathy and her team…
Konstantinos Lazaridis and I spoke with NPR Cathy Wurzer about the #exposome and #exposomics for new podcast from the Mayo Clinic. Cathy and her team…
Liked by Caghan Kizil
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I am deliriously happy to share that I have passed all four papers of the European Qualifying Examination (EQE)! I will soon be a fully qualified…
I am deliriously happy to share that I have passed all four papers of the European Qualifying Examination (EQE)! I will soon be a fully qualified…
Liked by Caghan Kizil
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Yanındayız Derneği olarak dün akşam birlikte yaz mevsimini karşıladık. Buluşmamızı onurlandıran üyelerimize, destekçilerimize, tüm dostlarımıza…
Yanındayız Derneği olarak dün akşam birlikte yaz mevsimini karşıladık. Buluşmamızı onurlandıran üyelerimize, destekçilerimize, tüm dostlarımıza…
Liked by Caghan Kizil
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"I told [my mom] I would do the talking for us. I learned to carry the relationship for both of us. I learned to love and express love for both of…
"I told [my mom] I would do the talking for us. I learned to carry the relationship for both of us. I learned to love and express love for both of…
Liked by Caghan Kizil
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After 4 years on The National Institutes of Health MNG Study Section, 2 years as Chair, I concluded my service this month. Over 1,000 applications;…
After 4 years on The National Institutes of Health MNG Study Section, 2 years as Chair, I concluded my service this month. Over 1,000 applications;…
Liked by Caghan Kizil
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