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Article ; Online: Macrophages: Potential Therapeutic Target of Myocardial Injury in COVID-19.

Nishiga, Masataka / Wu, Joseph C

2021 Volume 129, Issue 1, Page(s) 47–49

MeSH term(s)	COVID-19 ; Humans ; Macrophages ; Myocardium ; SARS-CoV-2
Language	English
Publishing date	2021-06-24
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.121.319446
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Article ; Online: Ferroptosis of Pacemaker Cells in COVID-19.

Nishiga, Masataka / Jahng, James W S / Wu, Joseph C

Circulation research

2022 Volume 130, Issue 7, Page(s) 978–980

MeSH term(s)	COVID-19 ; Cell Line, Tumor ; Ferroptosis ; Humans ; Myocytes, Cardiac
Language	English
Publishing date	2022-03-31
Publishing country	United States
Document type	Editorial ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.122.320951
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Article ; Online: Adverse Impact of Cannabis on Human Health.

Chandy, Mark / Nishiga, Masataka / Wei, Tzu-Tang / Hamburg, Naomi M / Nadeau, Kari / Wu, Joseph C

Annual review of medicine

2023 Volume 75, Page(s) 353–367

Abstract: Cannabis, the most commonly used recreational drug, is illicit in many areas of the world. With increasing decriminalization and legalization, cannabis use is increasing in the United States and other countries. The adverse effects of cannabis are ... ...

Abstract	Cannabis, the most commonly used recreational drug, is illicit in many areas of the world. With increasing decriminalization and legalization, cannabis use is increasing in the United States and other countries. The adverse effects of cannabis are unclear because its status as a Schedule 1 drug in the United States restricts research. Despite a paucity of data, cannabis is commonly perceived as a benign or even beneficial drug. However, recent studies show that cannabis has adverse cardiovascular and pulmonary effects and is linked with malignancy. Moreover, case reports have shown an association between cannabis use and neuropsychiatric disorders. With growing availability, cannabis misuse by minors has led to increasing incidences of overdose and toxicity. Though difficult to detect, cannabis intoxication may be linked to impaired driving and motor vehicle accidents. Overall, cannabis use is on the rise, and adverse effects are becoming apparent in clinical data sets.
MeSH term(s)	Humans ; Cannabis/adverse effects ; Drug Overdose
Language	English
Publishing date	2023-08-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207930-6
ISSN	1545-326X ; 0066-4219
ISSN (online)	1545-326X
ISSN	0066-4219
DOI	10.1146/annurev-med-052422-020627
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Article ; Online: The use of new CRISPR tools in cardiovascular research and medicine.

Nishiga, Masataka / Liu, Chun / Qi, Lei S / Wu, Joseph C

Nature reviews. Cardiology

2022 Volume 19, Issue 8, Page(s) 505–521

Abstract: Many novel CRISPR-based genome-editing tools, with a wide variety of applications, have been developed in the past few years. The original CRISPR-Cas9 system was developed as a tool to alter genomic sequences in living organisms in a simple way. However, ...

Abstract	Many novel CRISPR-based genome-editing tools, with a wide variety of applications, have been developed in the past few years. The original CRISPR-Cas9 system was developed as a tool to alter genomic sequences in living organisms in a simple way. However, the functions of new CRISPR tools are not limited to conventional genome editing mediated by non-homologous end-joining or homology-directed repair but expand into gene-expression control, epigenome editing, single-nucleotide editing, RNA editing and live-cell imaging. Furthermore, genetic perturbation screening by multiplexing guide RNAs is gaining popularity as a method to identify causative genes and pathways in an unbiased manner. New CRISPR tools can also be applied to ex vivo or in vivo therapeutic genome editing for the treatment of conditions such as hyperlipidaemia. In this Review, we first provide an overview of the diverse new CRISPR tools that have been developed to date. Second, we summarize how these new CRISPR tools are being used to study biological processes and disease mechanisms in cardiovascular research and medicine. Finally, we discuss the prospect of therapeutic genome editing by CRISPR tools to cure genetic cardiovascular diseases.
MeSH term(s)	CRISPR-Cas Systems ; Gene Editing/methods ; Humans ; RNA, Guide, CRISPR-Cas Systems/genetics ; RNA, Guide, CRISPR-Cas Systems/metabolism
Chemical Substances	RNA, Guide, CRISPR-Cas Systems
Language	English
Publishing date	2022-02-10
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2490375-9
ISSN	1759-5010 ; 1759-5002
ISSN (online)	1759-5010
ISSN	1759-5002
DOI	10.1038/s41569-021-00669-3
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Article ; Online: CRISPRi/a Screening with Human iPSCs.

Nishiga, Masataka / Qi, Lei S / Wu, Joseph C

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2320, Page(s) 261–281

Abstract: Identifying causative genes in a given phenotype or disease model is important for biological discovery and drug development. The recent development of the CRISPR/Cas9 system has enabled unbiased and large-scale genetic perturbation screens to identify ... ...

Abstract	Identifying causative genes in a given phenotype or disease model is important for biological discovery and drug development. The recent development of the CRISPR/Cas9 system has enabled unbiased and large-scale genetic perturbation screens to identify causative genes by knocking out many genes in parallel and selecting cells with desired phenotype of interest. However, compared to cancer cell lines, human somatic cells including cardiomyocytes (CMs), neuron cells, and endothelial cells are not easy targets of CRISPR screens because CRISPR screens require a large number of isogenic cells to be cultured and thus primary cells from patients are not ideal. The combination of CRISPR screens with induced pluripotent stem cell (iPSC) technology would be a powerful tool to identify causative genes and pathways because iPSCs can be expanded easily and differentiated to any cell type in principle. Here we describe a robust protocol for CRISPR screening using human iPSCs. Because each screening is different and needs to be customized depending on the cell types and phenotypes of interest, we show an example of CRISPR knockdown screening using CRISPRi system to identify essential genes to differentiate iPSCs to CMs.
MeSH term(s)	Base Sequence ; CRISPR-Cas Systems ; Causality ; Cells, Cultured ; Chromatography, Liquid/methods ; DNA/isolation & purification ; Doxycycline/pharmacology ; Flow Cytometry ; Gene Editing/methods ; Genetic Association Studies ; Genetic Vectors/genetics ; HEK293 Cells ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Induced Pluripotent Stem Cells/cytology ; Lentivirus/genetics ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; RNA, Guide, CRISPR-Cas Systems/genetics ; Transfection
Chemical Substances	RNA, Guide, CRISPR-Cas Systems ; DNA (9007-49-2) ; Doxycycline (N12000U13O)
Language	English
Publishing date	2021-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1484-6_23
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Article ; Online: Therapeutic genome editing in cardiovascular diseases.

Nishiga, Masataka / Qi, Lei S / Wu, Joseph C

Advanced drug delivery reviews

2020 Volume 168, Page(s) 147–157

Abstract: During the past decade, developments in genome editing technology have fundamentally transformed biomedical research. In particular, the CRISPR/Cas9 system has been extensively applied because of its simplicity and ability to alter genomic sequences ... ...

Abstract	During the past decade, developments in genome editing technology have fundamentally transformed biomedical research. In particular, the CRISPR/Cas9 system has been extensively applied because of its simplicity and ability to alter genomic sequences within living organisms, and an ever increasing number of CRISPR/Cas9-based molecular tools are being developed for a wide variety of applications. While genome editing tools have been used for many aspects of biological research, they also have enormous potential to be used for genome editing therapy to treat a broad range of diseases. For some hematopoietic diseases, clinical trials of therapeutic genome editing with CRISPR/Cas9 are already starting phase I. In the cardiovascular field, genome editing tools have been utilized to understand the mechanisms of diseases such as cardiomyopathy, arrythmia, and lipid metabolism, which now open the door to therapeutic genome editing. Currently, therapeutic genome editing in the cardiovascular field is centered on liver-targeting strategies to reduce cardiovascular risks. Targeting the heart is more challenging. In this review, we discuss the potential applications, recent advances, and current limitations of therapeutic genome editing in the cardiovascular field.
MeSH term(s)	Animals ; Cardiovascular Diseases/genetics ; Cardiovascular Diseases/therapy ; Clustered Regularly Interspaced Short Palindromic Repeats ; DNA Breaks, Double-Stranded ; DNA Repair/physiology ; Gene Editing/methods ; Humans ; Pluripotent Stem Cells/physiology
Language	English
Publishing date	2020-02-21
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2020.02.003
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Article ; Online: Induced pluripotent stem cells as a biopharmaceutical factory for extracellular vesicles.

Nishiga, Masataka / Guo, Hongchao / Wu, Joseph C

European heart journal

2018 Volume 39, Issue 20, Page(s) 1848–1850

MeSH term(s)	Biological Products ; Extracellular Vesicles ; Heart Failure ; Humans ; Induced Pluripotent Stem Cells ; Pluripotent Stem Cells
Chemical Substances	Biological Products
Language	English
Publishing date	2018-02-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehy097
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Article: Deciphering pathogenicity of variants of uncertain significance with CRISPR-edited iPSCs.

Guo, Hongchao / Liu, Lichao / Nishiga, Masataka / Cong, Le / Wu, Joseph C

Trends in genetics : TIG

2021 Volume 37, Issue 12, Page(s) 1109–1123

Abstract: Genetic variants play an important role in conferring risk for cardiovascular diseases (CVDs). With the rapid development of next-generation sequencing (NGS), thousands of genetic variants associated with CVDs have been identified by genome-wide ... ...

Abstract	Genetic variants play an important role in conferring risk for cardiovascular diseases (CVDs). With the rapid development of next-generation sequencing (NGS), thousands of genetic variants associated with CVDs have been identified by genome-wide association studies (GWAS), but the function of more than 40% of genetic variants is still unknown. This gap of knowledge is a barrier to the clinical application of the genetic information. However, determining the pathogenicity of a variant of uncertain significance (VUS) is challenging due to the lack of suitable model systems and accessible technologies. By combining clustered regularly interspaced short palindromic repeats (CRISPR) and human induced pluripotent stem cells (iPSCs), unprecedented advances are now possible in determining the pathogenicity of VUS in CVDs. Here, we summarize recent progress and new strategies in deciphering pathogenic variants for CVDs using CRISPR-edited human iPSCs.
MeSH term(s)	CRISPR-Cas Systems/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Gene Editing ; Genome-Wide Association Study ; Humans ; Induced Pluripotent Stem Cells ; Virulence
Language	English
Publishing date	2021-09-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2021.08.009
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Article: Cryo-electron tomography reveals the structural diversity of cardiac proteins in their cellular context.

Woldeyes, Rahel A / Nishiga, Masataka / Vander Roest, Alison S / Engel, Leeya / Giri, Prerna / Montenegro, Gabrielle C / Wu, Andrew C / Dunn, Alexander R / Spudich, James A / Bernstein, Daniel / Schmid, Michael F / Wu, Joseph C / Chiu, Wah

bioRxiv : the preprint server for biology

2023

Abstract: Cardiovascular diseases are a leading cause of death worldwide, but our understanding of the underlying mechanisms is limited, in part because of the complexity of the cellular machinery that controls the heart muscle contraction cycle. Cryogenic ... ...

Abstract	Cardiovascular diseases are a leading cause of death worldwide, but our understanding of the underlying mechanisms is limited, in part because of the complexity of the cellular machinery that controls the heart muscle contraction cycle. Cryogenic electron tomography (cryo-ET) provides a way to visualize diverse cellular machinery while preserving contextual information like subcellular localization and transient complex formation, but this approach has not been widely applied to the study of heart muscle cells (cardiomyocytes). Here, we deploy a platform for studying cardiovascular disease by combining cryo-ET with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). After developing a cryo-ET workflow for visualizing macromolecules in hiPSC-CMs, we reconstructed sub-nanometer resolution structures of the human thin filament, a central component of the contractile machinery. We also visualized a previously unobserved organization of a regulatory complex that connects muscle contraction to calcium signaling (the troponin complex), highlighting the value of our approach for interrogating the structures of cardiac proteins in their cellular context.
Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.26.564098
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Article ; Online: COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives.

Nishiga, Masataka / Wang, Dao Wen / Han, Yaling / Lewis, David B / Wu, Joseph C

Nature reviews. Cardiology

2020 Volume 17, Issue 9, Page(s) 543–558

Abstract: Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have ... ...

Abstract	Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.
MeSH term(s)	Betacoronavirus/physiology ; COVID-19 ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/physiopathology ; Comorbidity ; Coronavirus Infections/epidemiology ; Coronavirus Infections/metabolism ; Coronavirus Infections/physiopathology ; Disease Management ; Humans ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/physiopathology ; Risk Factors ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-07-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2490375-9
ISSN	1759-5010 ; 1759-5002
ISSN (online)	1759-5010
ISSN	1759-5002
DOI	10.1038/s41569-020-0413-9
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