Details of the Researcher

PHOTO

Sherif Mohamed Rashad
Section
Graduate School of Biomedical Engineering
Job title
Associate Professor
Degree

  • 博士（医学）（東北大学）

  • Ｍ．Ｓ．（アレクサンドリア大学）

Research History 4

  • 2023/04 - Present
    Tohoku University　Graduate School of Biomedical Engineering　Associate Professor

  • 2018/04 - 2023/03
    Tohoku University　Department of Neurosurgery, Graduate school of medicine　Assistant professor

  • 2014/10 - 2018/03
    Tohoku University　Department of Neurosurgery, Graduate school of medicine　PhD student

  • 2011/01 - 2014/09
    Alexandria University, Egypt　Department of Neurosurgery, Graduate school of medicine　Neurosurgical Resident doctor

Education 3

  • Tohoku University Graduate school of medicine　Neurosurgery　PhD course

    2014/10 - 2018/03

  • Alexandria University school of medicine　Neurosurgery　Master's course

    2010/10 - 2014/03

  • Alexandria University school of medicine　MBcch

    2001/09 - 2008/10

Research Interests 13

  • oxidative stress

  • neuron

  • Cell Death

  • Glioma

  • Epitranscriptome

  • tRNA

  • apoptosis

  • Moyamoya disease

  • computational flow dynamics

  • stem cell therapy

  • sphingosine-1-phosphate

  • brain aneurysm

  • Stroke

Research Areas 6

  • Life sciences / Laboratory animal science /

  • Life sciences / Cell biology /

  • Life sciences / Neurosurgery /

  • Life sciences / Molecular biology /

  • Life sciences / Neuroanatomy and physiology /

  • Life sciences / Neuroscience - general /

Papers 46

  1. Transcriptome-wide alternative mRNA splicing analysis reveals post-transcriptional regulation of neuronal differentiation. International-journal

    Yuan Zhou, Sherif Rashad, Kuniyasu Niizuma

    The FEBS journal　2025/01/24

    DOI： 10.1111/febs.17408 　

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    Alternative splicing (AS) plays an important role in neuronal development, function, and disease. Efforts to analyze the transcriptome of AS in neurons on a wide scale are currently limited. We characterized the transcriptome-wide AS changes in SH-SY5Y neuronal differentiation model, which is widely used to study neuronal function and disorders. Our analysis revealed global changes in five AS programs that drive neuronal differentiation. Motif analysis revealed the contribution of RNA-binding proteins (RBPs) to the regulation of AS during neuronal development. We concentrated on the primary alternative splicing program that occurs during differentiation, specifically on events involving exon skipping (SE). Motif analysis revealed motifs for polypyrimidine tract-binding protein 1 (PTB) and ELAV-like RNA binding protein 1 (HuR/ELAVL1) to be the top enriched in SE events, and their protein levels were downregulated after differentiation. shRNA knockdown of either PTB and HuR was associated with enhanced neuronal differentiation and transcriptome-wide exon skipping events that drive the process of differentiation. At the level of gene expression, we observed only modest changes, indicating predominant post-transcriptional effects of PTB and HuR. We also observed that both RBPs altered cellular responses to oxidative stress, in line with the differentiated phenotype observed after either gene knockdown. Our work characterizes the AS changes in a widely used and important model of neuronal development and neuroscience research and reveals intricate post-transcriptional regulation of neuronal differentiation.

  2. Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation. International-journal

    Daisuke Ando, Sherif Rashad, Thomas J Begley, Hidenori Endo, Masashi Aoki, Peter C Dedon, Kuniyasu Niizuma

    International journal of molecular sciences　26　(2)　2025/01/15

    DOI： 10.3390/ijms26020706 　

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    The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as well as codon optimality across seven mouse tissues. Our analysis revealed distinct enrichment patterns of tRNA modifications in different tissues. Queuosine (Q) tRNA modification was most enriched in the brain compared to other tissues, while mitochondrial tRNA modifications and tRNA expression were highest in the heart. Using this observation, we synthesized, and delivered in vivo, codon-mutated EGFP for Q-codons, where the C-ending Q-codons were replaced with U-ending codons. The protein levels of mutant EGFP were downregulated in liver, which is poor in Q, while in brain EGFP, levels did not change. These data show that understanding tRNA modification enrichments across tissues is not only essential for understanding codon decoding and bias but can also be utilized for optimizing gene and mRNA therapeutics to be more tissue-, cell-, or condition-specific.

  3. Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A. International-journal

    Yuan Zhou, Sherif Rashad, Daisuke Ando, Yuki Kobayashi, Teiji Tominaga, Kuniyasu Niizuma

    Journal of cellular physiology　2024/11/08

    DOI： 10.1002/jcp.31477 　

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    Neurons are exceptionally sensitive to oxidative stress, which is the basis for many neurodegenerative disease pathophysiologies. The posttranscriptional basis for neuronal differentiation and behavior is not well characterized. The steady-state levels of mRNA are outcomes of an interplay between RNA transcription and decay. However, the correlation between mRNA transcription, translation, and stability remains elusive. We utilized a SH-SY5Y-based neural differentiation model that is widely used to study neurodegenerative diseases. After neuronal differentiation, we observed enhanced sensitivity of mature neurons to mitochondrial stresses and ferroptosis induction. We employed a newly developed simplified mRNA stability profiling technique to explore the role of mRNA stability in SH-SY5Y neuronal differentiation model. Transcriptome-wide mRNA stability analysis revealed neural-specific RNA stability kinetics. Our analysis revealed that mRNA stability could either exert the buffering effect on gene products or change in the same direction as transcription. Importantly, we observed that changes in mRNA stability corrected over or under transcription of mRNAs to maintain mRNA translation dynamics. Furthermore, we conducted integrative analysis of our mRNA stability data set, and a published CRISPR-i screen focused on neuronal oxidative stress responses. Our analysis unveiled novel neuronal stress response genes that were not evident at the transcriptional or translational levels. SEPHS2 emerged as an important neuronal stress regulator based on this integrative analysis. Motif analysis unveiled SAMD4A as a major regulator of the dynamic changes in mRNA stability observed during differentiation. Knockdown of SAMD4A impaired neuronal differentiation and influenced the response to oxidative stress. Mechanistically, SAMD4A was found to alter the stability of several mRNAs. The novel insights into the interplay between mRNA stability and cellular behaviors provide a foundation for understanding neurodevelopmental processes and neurodegenerative disorders and highlight dynamic mRNA stability as an important layer of gene expression.

  4. Intravenous administration of muse cells improves cerebral ischemia outcome via immunomodulation in the spleen. International-journal

    Yuya Kato, Daiki Aburakawa, Ryosuke Tashiro, Yuan Zhou, Sherif Rashad, Hidenori Endo, Teiji Tominaga, Kuniyasu Niizuma

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism　271678X241290363　2024/10/13

    DOI： 10.1177/0271678X241290363 　

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    Ischemic stroke is a leading cause of disability and death globally. Stem cell therapies are emerging as a frontier for enhancing post-stroke recovery, with Muse cells-a subclass of pluripotent stem cells-demonstrating considerable promise. Muse cells are notable not only for their potential in cell replacement but also for their role in modulating immune responses following cerebral infarction. In the present study, we administered Muse cells intravenously to mice after inducing a stroke via distal middle cerebral artery occlusion. We evaluated motor outcomes, splenocyte populations, cytokine profiles, and gene expression 2 weeks after inducing stroke. Additionally, comparisons were drawn between outcomes in splenectomized mice and those receiving adoptive splenocyte transfer to discern the specific influence of the spleen on treatment efficacy. Our findings revealed that Muse cell therapy facilitates motor recovery, an effect that is compromised in the absence of the spleen. Spleens in treated mice exhibited a shift in neutrophil counts, increased cytokine activity, and a notable uptick in the expression of genes related to protein folding. These insights affirm the potential therapeutic effect of Muse cells in post-stroke treatment strategies, with their efficacy attributed, at least in part, to immunomodulatory pathways involving the spleen.

  5. High-throughput fluorescence lifetime imaging flow cytometry. International-journal

    Hiroshi Kanno, Kotaro Hiramatsu, Hideharu Mikami, Atsushi Nakayashiki, Shota Yamashita, Arata Nagai, Kohki Okabe, Fan Li, Fei Yin, Keita Tominaga, Omer Faruk Bicer, Ryohei Noma, Bahareh Kiani, Olga Efa, Martin Büscher, Tetsuichi Wazawa, Masahiro Sonoshita, Hirofumi Shintaku, Takeharu Nagai, Sigurd Braun, Jessica P Houston, Sherif Rashad, Kuniyasu Niizuma, Keisuke Goda

    Nature communications　15　(1)　7376-7376　2024/09/04

    DOI： 10.1038/s41467-024-51125-y 　

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    Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments.

  6. Translational response to mitochondrial stresses is orchestrated by tRNA modifications. International-journal

    Sherif Rashad, Shadi Al-Mesitef, Abdulrahman Mousa, Yuan Zhou, Daisuke Ando, Guangxin Sun, Tomoko Fukuuchi, Yuko Iwasaki, Jingdong Xiang, Shane R Byrne, Jingjing Sun, Masamitsu Maekawa, Daisuke Saigusa, Thomas J Begley, Peter C Dedon, Kuniyasu Niizuma

    bioRxiv : the preprint server for biology　2024/02/14

    DOI： 10.1101/2024.02.14.580389 　

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    Mitochondrial stress and dysfunction play important roles in many pathologies. However, how cells respond to mitochondrial stress is not fully understood. Here, we examined the translational response to electron transport chain (ETC) inhibition and arsenite induced mitochondrial stresses. Our analysis revealed that during mitochondrial stress, tRNA modifications (namely f5C, hm5C, queuosine and its derivatives, and mcm5U) dynamically change to fine tune codon decoding, usage, and optimality. These changes in codon optimality drive the translation of many pathways and gene sets, such as the ATF4 pathway and selenoproteins, involved in the cellular response to mitochondrial stress. We further examined several of these modifications using targeted approaches. ALKBH1 knockout (KO) abrogated f5C and hm5C levels and led to mitochondrial dysfunction, reduced proliferation, and impacted mRNA translation rates. Our analysis revealed that tRNA queuosine (tRNA-Q) is a master regulator of the mitochondrial stress response. KO of QTRT1 or QTRT2, the enzymes responsible for tRNA-Q synthesis, led to mitochondrial dysfunction, translational dysregulation, and metabolic alterations in mitochondria-related pathways, without altering cellular proliferation. In addition, our analysis revealed that tRNA-Q loss led to a domino effect on various tRNA modifications. Some of these changes could be explained by metabolic profiling. Our analysis also revealed that utilizing serum deprivation or alteration with Queuine supplementation to study tRNA-Q or stress response can introduce various confounding factors by altering many other tRNA modifications. In summary, our data show that tRNA modifications are master regulators of the mitochondrial stress response by driving changes in codon decoding.

  7. Codon usage and mRNA stability are translational determinants of cellular response to canonical ferroptosis inducers

    Sherif Rashad, Shane R Byrne, Daisuke Saigusa, Jingdong Xiang, Yuan Zhou, Liyin Zhang, Thomas J Begley, Teiji Tominaga, Kuniyasu Niizuma

    Neuroscience　2022/08

    Publisher: Elsevier BV

    DOI： 10.1016/j.neuroscience.2022.08.009 　

    ISSN： 0306-4522

  8. RNF213 loss of function reshapes vascular transcriptome and spliceosome leading to disrupted angiogenesis and aggravated vascular inflammatory responses. International-journal

    Liyin Zhang, Sherif Rashad, Yuan Zhou, Kuniyasu Niizuma, Teiji Tominaga

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism　42　(11)　271678X221110679-2122　2022/06/25

    DOI： 10.1177/0271678X221110679 　

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    RNF213 gene mutations are the cause behind Moyamoya disease, a rare cerebrovascular occlusive disease. However, the function of RNF213 in the vascular system and the impact of its loss of function are not yet comprehended. To understand RNF23 function, we performed gene knockdown (KD) in vascular cells and performed various phenotypical analysis as well as extensive transcriptome and epitranscriptome profiling. Our data revealed that RNF213 KD led to disrupted angiogenesis in HUVEC, in part due to downregulation of DNA replication and proliferation pathways. Furthermore, HUVEC cells became sensitive to LPS induced inflammation after RNF213 KD, leading to retarded cell migration and enhanced macrophage transmigration. This was evident at the level of transcriptome as well. Interestingly, RNF213 led to extensive changes in mRNA splicing that were not previously reported. In vascular smooth muscle cells (vSMCs), RNF213 KD led to alteration in cytoskeletal organization, contractility, and vSMCs function related pathways. Finally, RNF213 KD disrupted endothelial-to-vSMCs communication in co-culture models. Overall, our results indicate that RNF213 KD sensitizes endothelial cells to inflammation, leading to altered angiogenesis. Our results shed the light on the important links between RNF213 mutations and inflammatory/immune inducers of MMD and on the unexplored role of epitranscriptome in MMD.

  9. Dysregulation of Rnf 213 gene contributes to T cell response via antigen uptake, processing, and presentation. International-journal

    Ryosuke Tashiro, Kuniyasu Niizuma, Jun Kasamatsu, Yuko Okuyama, Sherif Rashad, Atsuo Kikuchi, Miki Fujimura, Shigeo Kure, Naoto Ishii, Teiji Tominaga

    Journal of cellular physiology　236　(11)　7554-7564　2021/05/10

    DOI： 10.1002/jcp.30396 　

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    Growing evidence suggest the association between Moyamoya disease (MMD) and immune systems, such as antigen presenting cells in particular. Rnf213 gene, a susceptibility gene for MMD, is highly expressed in immune tissues, however, its function remains unclear. In addition, the physiological role of RNF213 gene polymorphism c.14576G > A (rs112735431), susceptibility variant for MMD, is also poorly understood. By studying Rnf213-knockout (Rnf213-KO) mice with deletion of largest exon32 and Rnf213-knockin (Rnf213-KI) mice with insertion of single-nucleotide polymorphism corresponding to c.14576G > A mutation in MMD patients, we aimed to investigate the role of RNF213 in dendritic cell development, and antigen processing and presentation. First, we found a high level of Rnf213 gene expression in conventional DCs and monocytes. Second, flow cytometric and confocal microscopic analysis revealed ovalbumin protein-pulsed Rnf213-KO and Rnf213-KI DCs showed impaired antigen uptake, proteolysis and reduced numbers of endosomes and lysosomes, and thereby failed to activate and proliferate antigen-specific T cells efficiently. In addition, Rnf213-KI DCs showed a similar phenotype to that of Rnf213-KO BMDCs. In conclusion, our findings suggest the critical role of RNF213 in antigen uptake, processing and presentation.

  10. The cell and stress-specific canonical and noncanonical tRNA cleavage. International-journal

    Sherif Rashad, Teiji Tominaga, Kuniyasu Niizuma

    Journal of cellular physiology　236　(5)　3710-3724　2021/05

    DOI： 10.1002/jcp.30107 　

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    Following stress, transfer RNA (tRNA) is cleaved to generate tRNA halves (tiRNAs). These tiRNAs have been shown to repress protein translation. Angiogenin was considered the main enzyme that cleaves tRNA at its anticodon to generate 35-45 nucleotide long tiRNA halves, however, the recent reports indicate the presence of angiogenin-independent cleavage. We previously observed tRNA cleavage pattern occurring away from the anticodon site. To explore this noncanonical cleavage, we analyze tRNA cleavage patterns in rat model of ischemia-reperfusion and in two rat cell lines. In vivo mitochondrial tRNAs were prone to this noncanonical cleavage pattern. In vitro, however, cytosolic and mitochondrial tRNAs could be cleaved noncanonically. Our results show an important regulatory role of mitochondrial stress in angiogenin-mediated tRNA cleavage. Neither angiogenin nor RNH1 appear to regulate the noncanonical tRNA cleavage. Finally, we verified our previous findings of the role of Alkbh1 in regulating tRNA cleavage and its impact on noncanonical tRNA cleavage.

  11. Physiologic blood flow is turbulent. International-journal

    Khalid M Saqr, Simon Tupin, Sherif Rashad, Toshiki Endo, Kuniyasu Niizuma, Teiji Tominaga, Makoto Ohta

    Scientific reports　10　(1)　15492-15492　2020/09/23

    DOI： 10.1038/s41598-020-72309-8 　

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    Contemporary paradigm of peripheral and intracranial vascular hemodynamics considers physiologic blood flow to be laminar. Transition to turbulence is considered as a driving factor for numerous diseases such as atherosclerosis, stenosis and aneurysm. Recently, turbulent flow patterns were detected in intracranial aneurysm at Reynolds number below 400 both in vitro and in silico. Blood flow is multiharmonic with considerable frequency spectra and its transition to turbulence cannot be characterized by the current transition theory of monoharmonic pulsatile flow. Thus, we decided to explore the origins of such long-standing assumption of physiologic blood flow laminarity. Here, we hypothesize that the inherited dynamics of blood flow in main arteries dictate the existence of turbulence in physiologic conditions. To illustrate our hypothesis, we have used methods and tools from chaos theory, hydrodynamic stability theory and fluid dynamics to explore the existence of turbulence in physiologic blood flow. Our investigation shows that blood flow, both as described by the Navier-Stokes equation and in vivo, exhibits three major characteristics of turbulence. Womersley's exact solution of the Navier-Stokes equation has been used with the flow waveforms from HaeMod database, to offer reproducible evidence for our findings, as well as evidence from Doppler ultrasound measurements from healthy volunteers who are some of the authors. We evidently show that physiologic blood flow is: (1) sensitive to initial conditions, (2) in global hydrodynamic instability and (3) undergoes kinetic energy cascade of non-Kolmogorov type. We propose a novel modification of the theory of vascular hemodynamics that calls for rethinking the hemodynamic-biologic links that govern physiologic and pathologic processes.

  12. The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. International-journal Peer-reviewed

    Sherif Rashad, Xiaobo Han, Kanako Sato, Eikan Mishima, Takaaki Abe, Teiji Tominaga, Kuniyasu Niizuma

    RNA biology　1-12　2020/06/21

    DOI： 10.1080/15476286.2020.1779492 　

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    tiRNAs are small non-coding RNAs produced when tRNA is cleaved under stress. tRNA methylation modifications has emerged in recent years as important regulators for tRNA structural stability and sensitivity to cleavage and tiRNA generation during stress, however, the specificity and higher regulation of such a process is not fully understood. Alkbh1 is a m1A demethylase that leads to destabilization of tRNA and enhanced tRNA cleavage. We examined the impact of Alkbh1 targeting via gene knockdown or overexpression on B35 rat neuroblastoma cell line fate following stresses and on tRNA cleavage. We show that Alkbh1 impact on cell fate and tRNA cleavage is a stress specific process that is impacted by the demethylating capacity of the cellular stress in question. We also show that not all tRNAs are cleaved equally following Alkbh1 manipulation and stress, and that Alkbh1 KD fails to rescue tRNAs from cleavage following demethylating stresses. These findings shed a light on the specificity and higher regulation of tRNA cleavage and should act as a guide for future work exploring the utility of Alkbh1 as a therapeutic target for cancers or ischaemic insult.

  13. Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach. International-journal Peer-reviewed

    Sherif Rashad, Daisuke Saigusa, Takahiro Yamazaki, Yotaro Matsumoto, Yoshihisa Tomioka, Ritsumi Saito, Akira Uruno, Kuniyasu Niizuma, Masayuki Yamamoto, Teiji Tominaga

    Scientific reports　10　(1)　6507-6507　2020/04/16

    DOI： 10.1038/s41598-020-63483-w 　

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    Understanding the root causes of neuronal vulnerability to ischemia is paramount to the development of new therapies for stroke. Transient global cerebral ischemia (tGCI) leads to selective neuronal cell death in the CA1 sub-region of the hippocampus, while the neighboring CA3 sub-region is left largely intact. By studying factors pertaining to such selective vulnerability, we can develop therapies to enhance outcome after stroke. Using untargeted liquid chromatography-mass spectrometry, we analyzed temporal metabolomic changes in CA1 and CA3 hippocampal areas following tGCI in rats till the setting of neuronal apoptosis. 64 compounds in CA1 and 74 in CA3 were found to be enriched and statistically significant following tGCI. Pathway analysis showed that pyrimidine and purine metabolism pathways amongst several others to be enriched after tGCI in CA1 and CA3. Metabolomics analysis was able to capture very early changes following ischemia. We detected 6 metabolites to be upregulated and 6 to be downregulated 1 hour after tGCI in CA1 versus CA3. Several metabolites related to apoptosis and inflammation were differentially expressed in both regions after tGCI. We offer a new insight into the process of neuronal apoptosis, guided by metabolomic profiling that was not performed to such an extent previously.

  14. Author Correction: The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study. International-journal Peer-reviewed

    Sherif Rashad, Khalid M Saqr, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    Scientific reports　10　(1)　6217-6217　2020/04/07

    DOI： 10.1038/s41598-020-62862-7 　

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    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  15. Stress Induced tRNA Halves (tiRNAs) as Biomarkers for Stroke and Stroke Therapy; Pre-clinical Study. International-journal Peer-reviewed

    Kanako Sato, Sherif Rashad, Kuniyasu Niizuma, Teiji Tominaga

    Neuroscience　2020/03/19

    DOI： 10.1016/j.neuroscience.2020.03.018 　

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    tiRNAs are small non-coding RNAs generated by angiogenin-mediated tRNA cleavage during cellular stress. Some tiRNAs were shown to be cytoprotective, while other reports indicate that the generation of tiRNAs is cytotoxic. We used rat model of focal cerebral ischemia-reperfusion (I/R) injury to study the generation and regulation of tiRNAs following in vivo I/R and the impact of neuroprotective therapy on their generation. tiRNAs were induced after I/R and Minocycline therapy reduced global tiRNA levels. Our results showed that tRNA cleavage is tRNA species specific, and neuroprotective treatment does not affect all tiRNA species. We also evaluated the temporal changes in several tRNA modifying enzymes and showed a correlation between their expression and tRNA cleavage. In conclusion, we show that tiRNAs can serve as biomarkers for stroke and stroke therapy, further adding them to the repertoire of tools that can be used to monitor and treat stroke.

  16. The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study. International-journal Peer-reviewed

    Sherif Rashad, Khalid M Saqr, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    Scientific reports　10　(1)　3700-3700　2020/02/28

    DOI： 10.1038/s41598-020-60683-2 　

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    Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used high-resolution Large Eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.

  17. Octacalcium phosphate collagen composite (OCP/Col) enhance bone regeneration in a rat model of skull defect with dural defect. International-journal Peer-reviewed

    Takashi Sasaki, Kuniyasu Niizuma, Atsushi Kanoke, Keiko Matsui, Shogo Ogita, Sherif Rashad, Tadashi Kawai, Mika Watanabe, Hidenori Endo, Tetsu Takahashi, Shinji Kamakura, Teiji Tominaga

    Heliyon　6　(2)　e03347　2020/02

    DOI： 10.1016/j.heliyon.2020.e03347 　

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    Cranial bone defects are a major issue in the field of neurosurgery, and improper management of such defects can cause cosmetic issues as well as more serious infections and inflammation. Several strategies exist to manage these defects clinically, but most rely on synthetic materials that are prone to complications; thus, a bone regenerative approach would be superior. We tested a material (octacalcium phosphate collagen composite [OCP/Col]) that is known to enhance bone regeneration in a skull defect model in rats. Using a critical-sized rat skull defect model, OCP/Col was implanted in rats with an intact dura or with a partial defect of the dura. The results were compared with those in a no-treatment group over the course of 12 weeks using computed tomographic and histological analysis. OCP/Col enhanced bone regeneration, regardless of whether there was a defect of the dura. OCP/Col can be used to treat skull defects, even when the dura is injured or removed surgically, via bone regeneration with enhanced resorption of OCP/Col, thus limiting the risk of infection greatly.

  18. Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano-miRNAs. International-journal Peer-reviewed

    Sherif Rashad, Xiaobo Han, Khalid Saqr, Simon Tupin, Makoto Ohta, Kuniyasu Niizuma, Teiji Tominaga

    Journal of cellular physiology　2020/01/08

    DOI： 10.1002/jcp.29436 　

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    Endothelial cells (ECs) respond to flow stress via a variety of mechanisms, leading to various intracellular responses that can modulate the vessel wall and lead to diseases if the flow is disturbed. Mechano-microRNAs (miRNAs) are a subset of miRNAs in the ECs that are flow responsive. Mechano-miRNAs were shown to be related to atherosclerosis pathophysiology, and a number of them were identified as pathologic. Here, we exposed human carotid ECs to different wall shear stresses (WSS), high and low, and evaluated the response of miRNAs by microarray and quantitative polymerase chain reaction analysis. We discovered five new mechano-miRNAs that were not reported in that context previously to the best of our knowledge. Moreover, functional pathway analysis revealed that under low WSS conditions, several pathways regulating apoptosis are affected. In addition, KLF2 and KLF4, known atheroprotective genes, were downregulated under low WSS and upregulated under high WSS. KLF2 and VCAM1, both angiogenic, were upregulated under high WSS. NOS3, which is vascular protective, was also upregulated with higher WSS. On the contrary, ICAM-1 and E-selectin, both atherogenic and proinflammatory, were upregulated with high WSS. Collectively, the epigenetic landscape with the gene expression analysis reveals that low WSS is associated with a proapoptotic state, while high WSS is associated with a proliferative and proinflammatory state.

  19. tRNA cleavage: a new insight. International-journal Peer-reviewed

    Sherif Rashad, Kuniyasu Niizuma, Teiji Tominaga

    Neural regeneration research　15　(1)　47-52　2020/01

    DOI： 10.4103/1673-5374.264447 　

    ISSN： 1673-5374

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    Over the past decades, tRNA was found to be a rich hub of RNA modifications such as 1-methyladenosine and 5-methycytosine modifications and others, holding more than half of all modifications occurring in RNA molecules. Moreover, tRNA was discovered to be a source of various small noncoding RNA species, such as the stress induced angiogenin cleaved tRNA halves (tiRNA) or the miRNA like tRNA derived fragments. tRNA cleavage under stress was fist discovered in bacteria and later was found to be conserved across different species, including mammals. Under cellular stress conditions, tRNA undergoes conformational changes and angiogenin cleaves it into 3' and 5' halves. 5'tiRNA halves were shown to repress protein translations. tRNA cleavage is thought of to be a cytoprotective mechanism by which cells evade apoptosis, however some data hints to the opposite; that tiRNA are cytotoxic or at least related to apoptosis initiation. tRNA cleavage also was shown to be affected by tRNA modifications via different enzymes in the cytosol and mitochondria. In this review, we will highlight the biology of tRNA cleavage, show the evidence of it being cytoprotective or a marker of cell death and shed a light on its role in disease models and human diseases as well as possible future directions in this field of RNA research.

  20. A novel model of cerebral hyperperfusion with blood-brain barrier breakdown, white matter injury, and cognitive dysfunction. Peer-reviewed

    Mansour A, Rashad S, Niizuma K, Fujimura M, Tominaga T

    Journal of neurosurgery　1-13　2019/10

    DOI： 10.3171/2019.7.JNS19212 　

    ISSN： 0022-3085

  21. tiRNAs as a novel biomarker for cell damage assessment in in vitro ischemia-reperfusion model in rat neuronal PC12 cells. Peer-reviewed

    Elkordy A, Rashad S, Shehabeldeen H, Mishima E, Niizuma K, Abe T, Tominaga T

    Brain research　1714　8-17　2019/07

    DOI： 10.1016/j.brainres.2019.02.019 　

    ISSN： 0006-8993

  22. What does computational fluid dynamics tell us about intracranial aneurysms? A meta-analysis and critical review. Peer-reviewed

    Saqr KM, Rashad S, Tupin S, Niizuma K, Hassan T, Tominaga T, Ohta M

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism　271678X19854640　2019/06

    DOI： 10.1177/0271678X19854640 　

    ISSN： 0271-678X

  23. Neuroprotective effects of minocycline and progesterone on white matter injury after focal cerebral ischemia. Peer-reviewed

    Faheem H, Mansour A, Elkordy A, Rashad S, Shebl M, Madi M, Elwy S, Niizuma K, Tominaga T

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia　64　206-213　2019/04

    DOI： 10.1016/j.jocn.2019.04.012 　

    ISSN： 0967-5868

  24. ラット上矢静脈洞血栓症モデルにおける、脳血流変化の観察

    濱崎 亮, 新妻 邦泰, Rashad Sherif, 清水 宏明, 冨永 悌二

    脳循環代謝　30　(1)　114-114　2018/10

    Publisher: (一社)日本脳循環代謝学会

    ISSN： 0915-9401

    eISSN： 2188-7519

  25. A refined model of chronic cerebral hypoperfusion resulting in cognitive impairment and a low mortality rate in rats. International-journal Peer-reviewed

    Ahmed Mansour, Kuniyasu Niizuma, Sherif Rashad, Akira Sumiyoshi, Rie Ryoke, Hidenori Endo, Toshiki Endo, Kenichi Sato, Ryuta Kawashima, Teiji Tominaga

    Journal of neurosurgery　131　(3)　892-902　2018/09/07

    DOI： 10.3171/2018.3.JNS172274 　

    More details Close

    OBJECTIVE: The cognitive deficits of vascular dementia and the vasoocclusive state of moyamoya disease have often been mimicked with bilateral stenosis/occlusion of the common carotid artery (CCA) or internal carotid artery. However, the cerebral blood flow (CBF) declines abruptly in these models after ligation of the CCA, which differs from "chronic" cerebral hypoperfusion. While some modified but time-consuming techniques have used staged occlusion of both CCAs, others used microcoils for CCA stenosis, producing an adverse effect on the arterial endothelium. Thus, the authors developed a new chronic cerebral hypoperfusion (CCH) model with cognitive impairment and a low mortality rate in rats. METHODS: Male Sprague-Dawley rats were subjected to unilateral CCA occlusion and contralateral induction of CCA stenosis (modified CCA occlusion [mCCAO]) or a sham operation. Cortical regional CBF (rCBF) was measured using laser speckle flowmetry. Cognitive function was assessed using a Barnes circular maze (BCM). MRI studies were performed 4 weeks after the operation to evaluate cervical and intracranial arteries and parenchymal injury. Behavioral and histological studies were performed at 4 and 8 weeks after surgery. RESULTS: The mCCAO group revealed a gradual CBF reduction with a low mortality rate (2.3%). White matter degeneration was evident in the corpus callosum and corpus striatum. Although the cellular density declined in the hippocampus, MRI revealed no cerebral infarctions after mCCAO. Immunohistochemistry revealed upregulated inflammatory cells and angiogenesis in the hippocampus and cerebral cortex. Results of the BCM assessment indicated significant impairment in spatial learning and memory in the mCCAO group. Although some resolution of white matter injury was observed at 8 weeks, the animals still had cognitive impairment. CONCLUSIONS: The mCCAO is a straightforward method of producing a CCH model in rats. It is associated with a low mortality rate and could potentially be used to investigate vascular disease, moyamoya disease, and CCH. This model was verified for an extended time point of 8 weeks after surgery.

  26. A refined model of chronic cerebral hypoperfusion resulting in cognitive impairment and a low mortality rate in rat. Peer-reviewed

    sherif rashad, co-author

    J Neurosurg.　7　1-11　2018/09

  27. Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear Stress: The 2015 International Aneurysm CFD Challenge. Peer-reviewed

    sherif rashad, h co-author

    Cardiovasc Eng Technol.　2018/09

  28. Intracellular S1P Levels Dictate Fate of Different Regions of the Hippocampus following Transient Global Cerebral Ischemia Peer-reviewed

    Sherif Rashad, Kuniyasu Niizuma, Daisuke Saigusa, Xiaobo Han, Mika Sato-Maeda, Ritsumi Saito, Akira Uruno, Miki Fujimura, Shuntaro Ikawa, Masayuki Yamamoto, Teiji Tominaga

    Neuroscience　384　(384)　188-202　2018/08/01

    Publisher: Elsevier Ltd

    DOI： 10.1016/j.neuroscience.2018.05.015 　

    ISSN： 1873-7544 0306-4522

  29. Early BBB breakdown and subacute inflammasome activation and pyroptosis as a result of cerebral venous thrombosis. Peer-reviewed

    sherif rashad, First author

    brain research　2018/07

  30. Surgery for spinal intramedullary tumors: technique, outcome and factors affecting resectability. Peer-reviewed

    sherif rashad, First author

    Neurosurgical review　41　(2)　503-511　2018/04

  31. Impact of bifurcation angle and inflow coefficient on the rupture risk of bifurcation type basilar artery tip aneurysms Peer-reviewed

    Sherif Rashad, Shin-Ichiro Sugiyama, Kuniyasu Niizuma, Kenichi Sato, Hidenori Endo, Shunsuke Omodaka, Yasushi Matsumoto, Miki Fujimura, Teiji Tominaga

    Journal of Neurosurgery　128　(3)　723-730　2018/03/01

    Publisher: American Association of Neurological Surgeons

    DOI： 10.3171/2016.10.JNS161695 　

    ISSN： 1933-0693 0022-3085

  32. 神経アポトーシスにおけるS1Pシグナル伝達 虚血性細胞死に対する抵抗性と脆弱性への関連(S1P signaling in neuronal apoptosis: links to resistance and vulnerability to ischemic cell death)

    Rashad Sherif, 新妻 邦泰, 三枝 大輔, 韓 笑波, 前田 美香, 藤村 幹, 井川 俊太郎, 冨永 悌二

    脳循環代謝　29　(1)　215-215　2017/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN： 0915-9401

    eISSN： 2188-7519

  33. Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex Peer-reviewed

    Mika Sato-Maeda, Miki Fujimura, Sherif Rashad, Yuiko Morita-Fujimura, Kuniyasu Niizuma, Hiroyuki Sakata, Shuntaro Ikawa, Teiji Tominaga

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES　26　(9)　1904-1911　2017/09

    DOI： 10.1016/j.jstrokecerebrovasdis.2017.06.032 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  34. Uneven cerebral hemodynamic change as a cause of neurological deterioration in the acute stage after direct revascularization for moyamoya disease: cerebral hyperperfusion and remote ischemia caused by the 'watershed shift' Peer-reviewed

    Xian-kun Tu, Miki Fujimura, Sherif Rashad, Shunji Mugikura, Hiroyuki Sakata, Kuniyasu Niizuma, Teiji Tominaga

    NEUROSURGICAL REVIEW　40　(3)　507-512　2017/07

    DOI： 10.1007/s10143-017-0845-9 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  35. Stereotactic radiosurgery as a feasible treatment for intramedullary spinal arteriovenous malformations: a single-center observation Peer-reviewed

    Sherif Rashad, Toshiki Endo, Yoshihiro Ogawa, Kenichi Sato, Hidenori Endo, Yasushi Matsumoto, Akira Takahashi, Teiji Tominaga

    NEUROSURGICAL REVIEW　40　(2)　259-266　2017/04

    DOI： 10.1007/s10143-016-0758-z 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  36. Impact of bifurcation angle and inflow coefficient on rupture risk of bifurcation type basilar artery top aneurysms Invited

    sherif rashad, First author

    Transactions of Japanese Society for Medical and Biological Engineering　55　(5)　412-412　2017

    Publisher: Japanese Society for Medical and Biological Engineering

    DOI： 10.11239/jsmbe.55Annual.412 　

    More details Close

    <p>Risk factors for aneurysm rupture have been studied extensively in the past, with several factors showing significant correlations with rupture status. We analysed seventy-one basilar tip aneurysms were included in this study, 22 ruptured and 49 unruptured. Patient data (age and sex), morphometric factors (aneurysm maximum height and volume, aspect ratio, bifurcation angle, bottleneck ratio, and neck-parent artery ratio) and hemodynamic factors (inflow coefficient and wall shear stress) were compared between ruptured and unruptured groups, and statistically analyzed. Aspect ratio, bifurcation angle, bottleneck ratio, and inflow coefficient were significantly correlated with the rupture status on univariate analysis. Logistic regression analysis showed that aspect ratio and bifurcation angle were predictors of rupture. Bifurcation angle correlated inversely with inflow coefficient which in turn correlated directly with wall shear stress on Pearson's correlation coefficient Bifurcation angle and aspect ratio were independent predictors for aneurysm rupture.</p>

  37. Daughter Sac Formation Related to Blood Inflow Jet in an Intracranial Aneurysm Peer-reviewed

    Sin-ichiro Sugiyama, Hidenori Endo, Shunsuke Omodaka, Toshiki Endo, Kuniyasu Niizuma, Sherif Rashad, Toshio Nakayama, Kenichi Funamoto, Makoto Ohta, Teiji Tominaga

    WORLD NEUROSURGERY　96　396-402　2016/12

    DOI： 10.1016/j.wneu.2016.09.040 　

    ISSN： 1878-8750

    eISSN： 1878-8769

  38. Long-term follow-up of pediatric moyamoya disease treated by combined direct-indirect revascularization surgery: single institute experience with surgical and perioperative management Peer-reviewed

    Sherif Rashad, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

    NEUROSURGICAL REVIEW　39　(4)　615-622　2016/10

    DOI： 10.1007/s10143-016-0734-7 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  39. Blood Flow Into Basilar Tip Aneurysms: A Predictor for Recanalization After Coil Embolization Peer-reviewed

    Shin-ichiro Sugiyama, Kuniyasu Niizuma, Kenichi Sato, Sherif Rashad, Misaki Kohama, Hidenori Endo, Toshiki Endo, Yasushi Matsumoto, Makoto Ohta, Teiji Tominaga

    STROKE　47　(10)　2541-2547　2016/10

    DOI： 10.1161/STROKEAHA.116.013555 　

    ISSN： 0039-2499

    eISSN： 1524-4628

  40. Endovascular Modalities for the Treatment of Cavernous Sinus Arteriovenous Fistulas: A Single-Center Experience Peer-reviewed

    Tamer Hassan, Sherif Rashad, Waseem Aziz, Ahmed Sultan, Tamer Ibrahim

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES　24　(12)　2824-2838　2015/12

    DOI： 10.1016/j.jstrokecerebrovasdis.2015.08.016 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  41. De Novo Giant Partially Thrombosed Aneurysm Complicating STA-MCA Bypass Site in 3 Years: Case Report with Review of the Literature Peer-reviewed

    Sherif Rashad, Tamer Hassan, Hiroaki Shimizu, Tamer Ibrahim, Ahmed Sultan, Bassma El-Sabaa

    Neurosurgery Quarterly　25　(3)　296-301　2015/08/19

    Publisher: Lippincott Williams and Wilkins

    DOI： 10.1097/WNQ.0000000000000046 　

    ISSN： 1534-4916 1050-6438

  42. Therapeutic Clip Occlusion of the Anterior Choroidal Artery Involved with Partially Thrombosed Fusiform Aneurysm: A Case Report Peer-reviewed

    Sherif Rashad, Hidenori Endo, Ahmed Elsayed Sultan, Hiroaki Shimizu, Miki Fujimura, Kenichi Sato, Yasushi Matsumoto, Teiji Tominaga

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES　24　(8)　E227-E230　2015/08

    DOI： 10.1016/j.jstrokecerebrovasdis.2015.04.024 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  43. Management of spinal dural arterio-venous fistulas. Report of 12 cases and review of literature Peer-reviewed

    Sherif Rashad, Mohamed Abdel-Bary, Waseem Aziz, Tamer Hassan

    CLINICAL NEUROLOGY AND NEUROSURGERY　125　81-86　2014/10

    DOI： 10.1016/j.clineuro.2014.07.028 　

    ISSN： 0303-8467

    eISSN： 1872-6968

  44. Carotid artery occlusion for the treatment of symptomatic giant carotid aneurysms: a proposal of classification and surgical protocol Peer-reviewed

    Sherif Rashad, Tamer Hassan, Waseem Aziz, Ahmed Marei

    NEUROSURGICAL REVIEW　37　(3)　501-511　2014/07

    DOI： 10.1007/s10143-014-0533-y 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  45. Near fatal epistaxis from traumatic giant carotid artery pseudoaneurysm; case report. Peer-reviewed

    sherif rashad, First author

    Neurosurgery Quarterly　24　(1)　56-62　2014/02

    DOI： 10.1097/WNQ.0b013e31828cbed9 　

  46. Vein of Galen Aneurysmal Malformation Presented by Dementia and Impotence in an Adult: Case Report Peer-reviewed

    Sherif Rashad, Tamer Hassan

    NEUROSURGERY QUARTERLY　23　(2)　140-143　2013/05

    DOI： 10.1097/WNQ.0b013e31828c6f01 　

    ISSN： 1050-6438

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Misc. 3

  1. ラット静脈洞血栓症モデルにおける,脳血流変化の観察

    濱崎亮, 新妻邦泰, RASHAD Sherif, 高橋和孝, 清水宏明, 冨永悌二

    日本分子脳神経外科学会プログラム・抄録集　19th　2018

  2. ラット上矢静脈洞血栓症モデルにおける,脳血流変化の観察

    濱崎亮, 濱崎亮, 新妻邦泰, 新妻邦泰, RASHAD Sherif, 清水宏明, 冨永悌二

    脳循環代謝(Web)　30　(1)　2018

    ISSN： 2188-7519

  3. AVEC CFD2016

    安西眸, TUPIN Simon, 渡邉和浩, RASHAD Sherif, 太田信

    日本バイオレオロジー学会誌(Web)　30　(2)　2016

    ISSN： 2186-5663

Presentations 14

  1. BBB breakdown, neuroinflammation and widespread lipid disturbances caused by CVT in rats

    sherif rashad

    JNS 2018 – The 77th annual meeting of the Japanese neurosurgical society.　2018

  2. Impact of bifurcation angle and inflow coefficient on rupture risk of bifurcation type basilar artery aneurysms Invited

    sherif rashad

    JSMBE56 - The 56th Annual Meeting of Japanese Society for Medical and Biological Engineering　2017

  3. Impact of bifurcation angle and inflow coefficient on rupture risk of bifurcation type basilar artery top aneurysms Invited

    sherif rashad

    The 42nd Japan stroke society meeting (Stroke 2017), Osaka, Japan.　2017

  4. Conformational changes of tRNA in the hippocampal CA1 subregion after transient global cerebral ischemia in rats

    sherif rashad

    59th Japan cerebral blood flow and metabolism Society meeting (BRAIN Japan 2016), Tokoshima, Japan　2016

  5. Experimental model of chronic cerebral hypoperfusion in rats with gradual decreasement of cerebral blood flow and cognitive impairment

    sherif rashad (Co-presenter

    The 75th annual meeting of the Japanese neurosurgical society (JNS 2016), Fukouka, Japan　2016

  6. Conformational changes of tRNA in the hippocampal CA1 subregion after transient global cerebral ischemia in rats, roles in apoptosis and value as a stress marker

    sherif rashad

    The 75th annual meeting of the Japanese neurosurgical society (JNS 2016), Fukouka, Japan　2016

  7. Bifurcation configuration as a criterion affecting risk of aneurysm rupture in Basilar artery aneurysms International-presentation

    sherif rashad

    VII European Congress on Computational Methods in Applied Sciences and Engineering (ECCOMAS 2016), Crete, Greece　2016

  8. Determination of rupture status of MCA aneurysms using hemodynamic and geometric parameters.

    sherif rashad

    31th annual meeting of the Japanese Society for NeuroEndovascular Therapy (JSNET), Okayama, Japan 2015　2015

  9. Radiotherapy for intramedullary AVMs

    sherif rashad

    30th annual meeting of the Japanese society of spinal Surgery 2015 (jsss2015), Sapporo, Japan　2015

  10. Proposed Protocol for "where" to Occlude Giant Carotid Aneurysm with Mass Effect International-presentation

    sherif rashad

    World Live neurovascular conference 2014 (WLNC 2014), Buenos Aires, Argentina　2014

  11. De-novo Giant Partially Thrombosed Aneurysm Complicating Sta-mca Bypass Site in 3 Years; Case Report with Review of the Literature International-presentation

    sherif rashad

    15th World Federation of neurological surgeons 2013 (WFNS 2013), Seoul, South Korea　2013

  12. Vein of Galen Aneurysmal Malformation Presented by Dementia and Impotence in an Adult; Case Report International-presentation

    sherif rashad

    15th World Federation of neurological surgeons 2013 (WFNS 2013), Seoul, South Korea　2013

  13. Near Fatal Epistaxis from Traumatic Giant Carotid Artery Pseudoaneurysm; Case Report International-presentation

    sherif rashad

    15th World Federation of neurological surgeons 2013 (WFNS 2013), Seoul, South Korea　2013

  14. Recurrent near fatal epistaxis after parent vessel ligation from traumatic carotid pseudoaneurysm: case report

    sherif rashad

    28th meeting of the Japanese society for neuroendovascular therapy 2012 (JSNET 2012), Sendai, Japan　2012/11

Show all Show first 5