Full Text Journal Articles by
Author Ioannis Karakikes


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The Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.

Dries A M Feyen, Isaac Perea-Gil, Renee G C Maas, Magdalena Harakalova, Alexandra A Gavidia, Jennifer Arthur Ataam, Ting-Hsuan Wu, Aryan Vink, Jiayi Pei, Nirmal Vadgama, Albert J Suurmeijer, Wouter P Te Rijdt, Michelle Vu, Prashila L Amatya, Maricela Prado, Yuan Zhang, Logan Dunkenberger, Joost P G Sluijter, Karim Sallam, Folkert W Asselbergs, Mark Mercola, Ioannis Karakikes,

<b>Background:</b> Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy (DCM) with a high prevalence of ventricular arrhythmias. How the R14 deletion causes DCM is poorly understood and there are ... Read more >>

Circulation (Circulation)
[2021, :]

Cited: 0 times

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Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.

Jiongjia Cheng, Masanao Tsuda, Karl Okolotowicz, Mary Dwyer, Paul J Bushway, Alexandre R Colas, Joseph J Lancman, Dennis Schade, Isaac Perea-Gil, Arne A N Bruyneel, Jaechol Lee, Nirmal Vadgama, Justine Quach, Wesley L McKeithan, Travis L Biechele, Joseph C Wu, Randall T Moon, P Duc Si Dong, Ioannis Karakikes, John R Cashman, Mark Mercola,

Wnt signaling plays a central role in tissue maintenance and cancer. Wnt activates downstream genes through β-catenin, which interacts with TCF/LEF transcription factors. A major question is how this signaling is coordinated relative to tissue organization and renewal. We used a recently described class of small molecules that binds tubulin ... Read more >>

Cell Chem Biol (Cell chemical biology)
[2021, 28(5):625-635.e5]

Cited: 0 times

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A Novel Recessive Mutation in SPEG Causes Early Onset Dilated Cardiomyopathy.

Aviva Levitas, Emad Muhammad, Yuan Zhang, Isaac Perea Gil, Ricardo Serrano, Nashielli Diaz, Maram Arafat, Alexandra A Gavidia, Michael S Kapiloff, Mark Mercola, Yoram Etzion, Ruti Parvari, Ioannis Karakikes,

Dilated cardiomyopathy (DCM) is a common cause of heart failure and sudden cardiac death. It has been estimated that up to half of DCM cases are hereditary. Mutations in more than 50 genes, primarily autosomal dominant, have been reported. Although rare, recessive mutations are thought to contribute considerably to DCM, ... Read more >>

PLoS Genet (PLoS genetics)
[2020, 16(9):e1009000]

Cited: 3 times

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Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates.

Kitchener D Wilson, Mohamed Ameen, Hongchao Guo, Oscar J Abilez, Lei Tian, Maxwell R Mumbach, Sebastian Diecke, Xulei Qin, Yonggang Liu, Huaxiao Yang, Ning Ma, Sadhana Gaddam, Nathan J Cunningham, Mingxia Gu, Evgenios Neofytou, Maricela Prado, Thomas B Hildebrandt, Ioannis Karakikes, Howard Y Chang, Joseph C Wu,

Transposable elements (TEs) comprise nearly half of the human genome and are often transcribed or exhibit cis-regulatory properties with unknown function in specific processes such as heart development. In the case of endogenous retroviruses (ERVs), a TE subclass, experimental interrogation is constrained as many are primate-specific or human-specific. Here, we ... Read more >>

Dev Cell (Developmental cell)
[2020, 54(6):694-709.e9]

Cited: 3 times

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Translating genomic insights into cardiovascular medicines: Opportunities and challenges of CRISPR-Cas9.

Yuan Zhang, Ioannis Karakikes,

The growing appreciation of human genetics and genomics in cardiovascular disease (CVD) accompanied by the technological breakthroughs in genome editing, particularly the CRISPR-Cas9 technologies, has presented an unprecedented opportunity to explore the application of genome editing in cardiovascular medicine. The ever-growing genome editing toolbox includes an assortment of CRISPR-Cas systems ... Read more >>

Trends Cardiovasc Med (Trends in cardiovascular medicine)
[2020, :]

Cited: 0 times

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Molecular Signatures of Beneficial Class Effects of Statins on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Lei Tian, Angelos Oikonomopoulos, Chun Liu, Tomoya Kitani, Rajani Shrestha, Christopher L Chen, Sang-Ging Ong, Mark Smeets, Ioannis Karakikes, Nazish Sayed, Joseph C Wu,

Circulation (Circulation)
[2020, 141(14):1208-1210]

Cited: 1 time

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AlleleProfileR: A versatile tool to identify and profile sequence variants in edited genomes.

Arne A N Bruyneel, Alexandre R Colas, Ioannis Karakikes, Mark Mercola,

Gene editing strategies, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9), are revolutionizing biology. However, quantitative and sensitive detection of targeted mutations are required to evaluate and quantify the genome editing outcomes. Here we present AlleleProfileR, a new analysis tool, ... Read more >>

PLoS One (PloS one)
[2019, 14(12):e0226694]

Cited: 1 time

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Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy.

Jaecheol Lee, Vittavat Termglinchan, Sebastian Diecke, Ilanit Itzhaki, Chi Keung Lam, Priyanka Garg, Edward Lau, Matthew Greenhaw, Timon Seeger, Haodi Wu, Joe Z Zhang, Xingqi Chen, Isaac Perea Gil, Mohamed Ameen, Karim Sallam, June-Wha Rhee, Jared M Churko, Rinkal Chaudhary, Tony Chour, Paul J Wang, Michael P Snyder, Howard Y Chang, Ioannis Karakikes, Joseph C Wu,

Lamin A/C (LMNA) is one of the most frequently mutated genes associated with dilated cardiomyopathy (DCM). DCM related to mutations in LMNA is a common inherited cardiomyopathy that is associated with systolic dysfunction and cardiac arrhythmias. Here we modelled the LMNA-related DCM in vitro using patient-specific induced pluripotent stem cell-derived ... Read more >>

Nature (Nature)
[2019, 572(7769):335-340]

Cited: 34 times

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Concise Review: Precision Matchmaking: Induced Pluripotent Stem Cells Meet Cardio-Oncology.

Pooja Nair, Maricela Prado, Isaac Perea-Gil, Ioannis Karakikes,

As common chemotherapeutic agents are associated with an increased risk of acute and chronic cardiovascular complications, a new clinical discipline, cardio-oncology, has recently emerged. At the same time, the development of preclinical human stem cell-derived cardiovascular models holds promise as a more faithful platform to predict the cardiovascular toxicity of ... Read more >>

Stem Cells Transl Med (Stem cells translational medicine)
[2019, 8(8):758-767]

Cited: 2 times

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A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay.

Timon Seeger, Rajani Shrestha, Chi Keung Lam, Caressa Chen, Wesley L McKeithan, Edward Lau, Alexa Wnorowski, George McMullen, Matthew Greenhaw, Jaecheol Lee, Angelos Oikonomopoulos, Soah Lee, Huaxiao Yang, Mark Mercola, Matthew Wheeler, Euan A Ashley, Fan Yang, Ioannis Karakikes, Joseph C Wu,

<h4>Background</h4>Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in myosin-binding protein C3 ( MYBPC3) resulting in a premature termination codon (PTC). The underlying mechanisms of how PTC mutations in MYBPC3 lead to the onset and progression of HCM are poorly understood. This study's aim was to investigate the molecular mechanisms ... Read more >>

Circulation (Circulation)
[2019, 139(6):799-811]

Cited: 23 times

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Telomere shortening is a hallmark of genetic cardiomyopathies.

Alex C Y Chang, Andrew C H Chang, Anna Kirillova, Koki Sasagawa, Willis Su, Gerhard Weber, Jue Lin, Vittavat Termglinchan, Ioannis Karakikes, Timon Seeger, Alexandra M Dainis, John T Hinson, Jonathan Seidman, Christine E Seidman, John W Day, Euan Ashley, Joseph C Wu, Helen M Blau,

This study demonstrates that significantly shortened telomeres are a hallmark of cardiomyocytes (CMs) from individuals with end-stage hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) as a result of heritable defects in cardiac proteins critical to contractile function. Positioned at the ends of chromosomes, telomeres are DNA repeats that serve as ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2018, 115(37):9276-9281]

Cited: 19 times

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Recent Progress in Genome Editing Approaches for Inherited Cardiovascular Diseases.

Balpreet Kaur, Isaac Perea-Gil, Ioannis Karakikes,

PURPOSE OF REVIEW:This review describes the recent progress in nuclease-based therapeutic applications for inherited heart diseases in vitro, highlights the development of the most recent genome editing technologies and discusses the associated challenges for clinical translation. RECENT FINDINGS:Inherited cardiovascular disorders are passed from generation to generation. Over the past decade, ... Read more >>

Curr Cardiol Rep (Current cardiology reports)
[2018, 20(7):58]

Cited: 2 times

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SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation.

Jaecheol Lee, Ning-Yi Shao, David T Paik, Haodi Wu, Hongchao Guo, Vittavat Termglinchan, Jared M Churko, Youngkyun Kim, Tomoya Kitani, Ming-Tao Zhao, Yue Zhang, Kitchener D Wilson, Ioannis Karakikes, Michael P Snyder, Joseph C Wu,

Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation ... Read more >>

Cell Stem Cell (Cell stem cell)
[2018, 22(3):428-444.e5]

Cited: 14 times

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Passive Stretch Induces Structural and Functional Maturation of Engineered Heart Muscle as Predicted by Computational Modeling.

Oscar J Abilez, Evangeline Tzatzalos, Huaxiao Yang, Ming-Tao Zhao, Gwanghyun Jung, Alexander M Zöllner, Malte Tiburcy, Johannes Riegler, Elena Matsa, Praveen Shukla, Yan Zhuge, Tony Chour, Vincent C Chen, Paul W Burridge, Ioannis Karakikes, Ellen Kuhl, Daniel Bernstein, Larry A Couture, Joseph D Gold, Wolfram H Zimmermann, Joseph C Wu,

The ability to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes (CMs) makes them an attractive source for repairing injured myocardium, disease modeling, and drug testing. Although current differentiation protocols yield hPSC-CMs to >90% efficiency, hPSC-CMs exhibit immature characteristics. With the goal of overcoming this limitation, we tested the effects ... Read more >>

Stem Cells (Stem cells (Dayton, Ohio))
[2018, 36(2):265-277]

Cited: 35 times

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Molecular and functional resemblance of differentiated cells derived from isogenic human iPSCs and SCNT-derived ESCs.

Ming-Tao Zhao, Haodong Chen, Qing Liu, Ning-Yi Shao, Nazish Sayed, Hung-Ta Wo, Joe Z Zhang, Sang-Ging Ong, Chun Liu, Youngkyun Kim, Huaxiao Yang, Tony Chour, Hong Ma, Nuria Marti Gutierrez, Ioannis Karakikes, Shoukhrat Mitalipov, Michael P Snyder, Joseph C Wu,

Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear reprogramming by transcription factors (i.e., induced pluripotent stem cells, iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and preclinical application of differentiated cells generated by different reprogramming mechanisms have yet to be evaluated. Here we investigated the molecular ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2017, 114(52):E11111-E11120]

Cited: 22 times

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A Comprehensive TALEN-Based Knockout Library for Generating Human-Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases.

Ioannis Karakikes, Vittavat Termglinchan, Diana A Cepeda, Jaecheol Lee, Sebastian Diecke, Ayal Hendel, Ilanit Itzhaki, Mohamed Ameen, Rajani Shrestha, Haodi Wu, Ning Ma, Ning-Yi Shao, Timon Seeger, Nicole Woo, Kitchener D Wilson, Elena Matsa, Matthew H Porteus, Vittorio Sebastiano, Joseph C Wu,

<h4>Rationale</h4>Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome.<h4>Objective</h4>The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases ... Read more >>

Circ Res (Circulation research)
[2017, 120(10):1561-1571]

Cited: 27 times

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Efficient Genome Editing in Induced Pluripotent Stem Cells with Engineered Nucleases In Vitro.

Vittavat Termglinchan, Timon Seeger, Caressa Chen, Joseph C Wu, Ioannis Karakikes,

Precision genome engineering is rapidly advancing the application of the induced pluripotent stem cells (iPSCs) technology for in vitro disease modeling of cardiovascular diseases. Targeted genome editing using engineered nucleases is a powerful tool that allows for reverse genetics, genome engineering, and targeted transgene integration experiments to be performed in ... Read more >>

Methods Mol Biol (Methods in molecular biology (Clifton, N.J.))
[2017, 1521:55-68]

Cited: 3 times

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Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells.

Francesca Stillitano, Jens Hansen, Chi-Wing Kong, Ioannis Karakikes, Christian Funck-Brentano, Lin Geng, Stuart Scott, Stephan Reynier, Ma Wu, Yannick Valogne, Carole Desseaux, Joe-Elie Salem, Dorota Jeziorowska, Noël Zahr, Ronald Li, Ravi Iyengar, Roger J Hajjar, Jean-Sébastien Hulot,

A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel ... Read more >>

Elife (eLife)
[2017, 6:]

Cited: 24 times

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Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics.

Caressa Chen, Vittavat Termglinchan, Ioannis Karakikes,

Heart failure (HF), a common sequela of cardiovascular diseases, remains a staggering clinical problem, associated with high rates of morbidity and mortality worldwide. Advances in pharmacological, interventional, and operative management have improved patient care, but these interventions are insufficient to halt the progression of HF, particularly the end-stage irreversible loss ... Read more >>

Stem Cells (Stem cells (Dayton, Ohio))
[2017, 35(5):1131-1140]

Cited: 7 times

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Gene Transfer in Cardiomyocytes Derived from ES and iPS Cells.

Francesca Stillitano, Ioannis Karakikes, Roger J Hajjar,

The advent of human induced pluripotent stem cell (hiPSC) technology has produced patient-specific hiPSC derived cardiomyocytes (hiPSC-CMs) that can be used as a platform to study cardiac diseases and to explore new therapies.The ability to genetically manipulate hiPSC-CMs not only is essential for identifying the structural and/or functional role of ... Read more >>

Methods Mol Biol (Methods in molecular biology (Clifton, N.J.))
[2017, 1521:183-193]

Cited: 2 times

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Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers.

Mingxia Gu, Ning-Yi Shao, Silin Sa, Dan Li, Vittavat Termglinchan, Mohamed Ameen, Ioannis Karakikes, Gustavo Sosa, Fabian Grubert, Jaecheol Lee, Aiqin Cao, Shalina Taylor, Yu Ma, Zhixin Zhao, James Chappell, Rizwan Hamid, Eric D Austin, Joseph D Gold, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch,

In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers that alleviate the disease. Here, we used comparison of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from three families with unaffected mutation carriers (UMCs), FPAH patients, and gender-matched controls ... Read more >>

Cell Stem Cell (Cell stem cell)
[2017, 20(4):490-504.e5]

Cited: 78 times

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Genomic correction of familial cardiomyopathy in human engineered cardiac tissues.

Francesca Stillitano, Irene C Turnbull, Ioannis Karakikes, Mathieu Nonnenmacher, Peter Backeris, Jean-Sébastien Hulot, Evangelia G Kranias, Roger J Hajjar, Kevin D Costa,

In this study, we used three-dimensional human engineered cardiac tissue technology to directly show that phospholamban (PLN) R14del mutation impairs cardiac contractility and to demonstrate restoration of contractile properties with targeted genetic correction of this inheritable form of dilated cardiomyopathy. ... Read more >>

Eur Heart J (European heart journal)
[2016, 37(43):3282-3284]

Cited: 25 times

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Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction.

Tatiana Kuznetsova, Francois Haddad, Judita Knez, Yael Rosenberg-Hasson, Janine Sung, Nicholas Cauwenberghs, Lutgarde Thijs, Ioannis Karakikes, Holden Maecker, Kenneth W Mahaffey, Joseph C Wu, Jan A Staessen,

There is strong evidence that inflammatory mediators play a key role in the progression to heart failure in patients with systemic hypertension (HTN). The present study aimed to identify a set of cytokines that are associated with early left ventricular (LV) remodeling and dysfunction as captured by echocardiography in patients ... Read more >>

J Am Soc Hypertens (Journal of the American Society of Hypertension : JASH)
[2015, 9(12):975-84.e3]

Cited: 9 times

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A Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next-Generation Sequencing Assay for Inherited Heart Diseases.

Kitchener D Wilson, Peidong Shen, Eula Fung, Ioannis Karakikes, Angela Zhang, Kolsoum InanlooRahatloo, Justin Odegaard, Karim Sallam, Ronald W Davis, George K Lui, Euan A Ashley, Curt Scharfe, Joseph C Wu,

<h4>Rationale</h4>Thousands of mutations across >50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited because many sequencing services and off-the-shelf kits suffer from slow turnaround, inefficient capture of genomic DNA, and high cost. Furthermore, customization of these assays to cover emerging ... Read more >>

Circ Res (Circulation research)
[2015, 117(7):603-611]

Cited: 16 times

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Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes.

Ioannis Karakikes, Mohamed Ameen, Vittavat Termglinchan, Joseph C Wu,

Disease models are essential for understanding cardiovascular disease pathogenesis and developing new therapeutics. The human induced pluripotent stem cell (iPSC) technology has generated significant enthusiasm for its potential application in basic and translational cardiac research. Patient-specific iPSC-derived cardiomyocytes offer an attractive experimental platform to model cardiovascular diseases, study the earliest ... Read more >>

Circ Res (Circulation research)
[2015, 117(1):80-88]

Cited: 153 times

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