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52. RARG variant predictive of doxorubicin-induced cardiotoxicity identifies a cardioprotective therapy

Author

Magdy, Tarek, primary, Jiang, Zhengxin, additional, Jouni, Mariam, additional, Fonoudi, Hananeh, additional, Lyra-Leite, Davi, additional, Jung, Gwanghyun, additional, Romero-Tejeda, Marisol, additional, Kuo, Hui-Hsuan, additional, Fetterman, K. Ashley, additional, Gharib, Mennat, additional, Burmeister, Brian T., additional, Zhao, Mingming, additional, Sapkota, Yadav, additional, Ross, Colin J., additional, Carleton, Bruce C., additional, Bernstein, Daniel, additional, and Burridge, Paul W., additional

Published
2021
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57. Targeting the Microtubule EB1-CLASP2 Complex Modulates Na V 1.5 at Intercalated Discs

Author

Marchal, Gerard A., primary, Jouni, Mariam, additional, Chiang, David Y., additional, Pérez-Hernández, Marta, additional, Podliesna, Svitlana, additional, Yu, Nuo, additional, Casini, Simona, additional, Potet, Franck, additional, Veerman, Christiaan C., additional, Klerk, Mischa, additional, Lodder, Elisabeth M., additional, Mengarelli, Isabella, additional, Guan, Kaomei, additional, Vanoye, Carlos G., additional, Rothenberg, Eli, additional, Charpentier, Flavien, additional, Redon, Richard, additional, George, Alfred L., additional, Verkerk, Arie O., additional, Bezzina, Connie R., additional, MacRae, Calum A., additional, Burridge, Paul W., additional, Delmar, Mario, additional, Galjart, Niels, additional, Portero, Vincent, additional, and Remme, Carol Ann, additional

Published
2021
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59. Generating a Cost-Effective Weekend-Free Chemically Defined hiPSC Culture Medium

Author

Fonoudi, Hananeh, Lyra-Leite, Davi M., Javed, Hoor A., and Burridge, Paul W.

Subjects
Induced Pluripotent Stem Cells, Cell Culture Techniques, Humans, Article, Cells, Cultured, Culture Media
Abstract

We have previously developed a cost-effective chemically defined medium formula for weekend-free culture of human induced pluripotent stem cells (hiPSCs), costing ∼3% of the price of commercial medium. This medium, which we termed B8, is specifically optimized for robust and fast growth of hiPSCs and for a weekend-free medium change regimen. We demonstrated that this medium is suitable for reprogramming of somatic cells into hiPSCs and for differentiation into a variety of lineages. Here, we provide a protocol for simple generation of the most cost-effective variant of this medium, along with a protocol for making Matrigel-coated plates and culturing, passaging, cryopreserving, and thawing hiPSCs. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Preparation of a highly optimized, robust, and cost-effective human induced pluripotent stem cell culture medium Basic Protocol 2: Weekend-free maintenance and passaging of human induced pluripotent stem cells in B8 medium.

Published
2020

63. Genetic Variants Associated with Therapy-Related Cardiomyopathy among Childhood Cancer Survivors of African Ancestry

Author

Sapkota, Yadav, primary, Qin, Na, additional, Ehrhardt, Matthew J., additional, Wang, Zhaoming, additional, Chen, Yan, additional, Wilson, Carmen L., additional, Estepp, Jeremie, additional, Rai, Parul, additional, Hankins, Jane S., additional, Burridge, Paul W., additional, Jefferies, John L., additional, Zhang, Jinghui, additional, Hudson, Melissa M., additional, Robison, Leslie L., additional, Armstrong, Gregory T., additional, Mulrooney, Daniel A., additional, and Yasui, Yutaka, additional

Published
2020
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65. A physical map of the mouse genome

Author

Gregory, Simon G., Sekhon, Mandeep, Schein, Jacqueline, Zhao, Shaying, Osoegawa, Kazutoyo, Scott, Carol E., Evans, Richard S., Burridge, Paul W., Cox, Tony V., Fox, Christopher A., Hutton, Richard D., Mullenger, Ian R., Phillips, Kimbly J., Smith, James, Stalker, Jim, Threadgold, Glen J., Birney, Ewan, Wylie, Kristine, Chinwalla, Asif, Wallis, John, Hillier, LaDeana, Carter, Jason, Gaige, Tony, Jaeger, Sara, Kremitzki, Colin, Layman, Dan, Maas, Jason, McGrane, Rebecca, Mead, Kelly, Walker, Rebecca, Jones, Steven, Smith, Michael, Asano, Jennifer, Bosdet, Ian, Chan, Susanna, Chittaranjan, Suganthi, Chiu, Readman, Fjell, Chris, Fuhrmann, Dan, Girn, Noreen, Gray, Catharine, Guin, Ran, Hsiao, Letticia, Krzywinski, Martin, Kutsche, Reta, Lee, Soo Sen, Mathewson, Carrie, McLeavy, Candice, Messervier, Steve, Ness, Steven, Pandoh, Pawan, Prabhu, Anna-Liisa, Saeedi, Parvaneh, Smailus, Duane, Spence, Lorraine, Stott, Jeff, Taylor, Sheryl, Terpstra, Wesley, Tsai, Miranda, Vardy, Jill, Wye, Natasja, Yang, George, Shatsman, Sofiya, Ayodeji, Bola, Geer, Keita, Tsegaye, Getahun, Shvartsbeyn, Alla, Gebregeorgis, Elizabeth, Krol, Margaret, Russell, Daniel, Overton, Larry, Malek, Joel A., Holmes, Mike, Heaney, Michael, Shetty, Jyoti, Feldblyum, Tamara, Nierman, William C., Catanese, Joseph J., Hubbard, Tim, Waterston, Robert H., Rogers, Jane, de Jong, Pieter J., Fraser, Claire M., Marra, Marco, McPherson, John D., and Bentley, David R.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy., Author(s): Simon G. Gregory [1]; Mandeep Sekhon [2]; Jacqueline Schein [3]; Shaying Zhao [4]; Kazutoyo Osoegawa [5]; Carol E. Scott [1]; Richard S. Evans [1]; Paul W. Burridge [1]; Tony [...]

Published
2002

71. Negligible-Cost and Weekend-Free Chemically Defined Human iPSC Culture

Author

Kuo, Hui-Hsuan, primary, Gao, Xiaozhi, additional, DeKeyser, Jean-Marc, additional, Fetterman, K. Ashley, additional, Pinheiro, Emily A., additional, Weddle, Carly J., additional, Fonoudi, Hananeh, additional, Orman, Michael V., additional, Romero-Tejeda, Marisol, additional, Jouni, Mariam, additional, Blancard, Malorie, additional, Magdy, Tarek, additional, Epting, Conrad L., additional, George, Alfred L., additional, and Burridge, Paul W., additional

Published
2020
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72. Physiological stress improves stem cell modeling of dystrophic cardiomyopathy

Author

Fullenkamp, Dominic E., Willis, Alexander B., Curtin, Jodi L., Amaral, Ansel P., Dittloff, Kyle T., Harris, Sloane I., Chychula, Ivana A., Holgren, Cory W., Burridge, Paul W., Russell, Brenda, Demonbreun, Alexis R., and McNally, Elizabeth M.

Abstract

Heart failure contributes to Duchenne muscular dystrophy (DMD), which arises from mutations that ablate dystrophin, rendering the plasma membrane prone to disruption. Cardiomyocyte membrane breakdown in patients with DMD yields a serum injury profile similar to other types of myocardial injury with the release of creatine kinase and troponin isoforms. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are highly useful but can be improved. We generated hiPSC-CMs from a patient with DMD and subjected these cells to equibiaxial mechanical strain to mimic in vivo stress. Compared to healthy cells, DMD hiPSC-CMs demonstrated greater susceptibility to equibiaxial strain after 2 h at 10% strain. We generated an aptamer-based profile of proteins released from hiPSC-CMs both at rest and subjected to strain and identified a strong correlation in the mechanical stress-induced proteome from hiPSC-CMs and serum from patients with DMD. We exposed hiPSC-CMs to recombinant annexin A6, a protein resealing agent, and found reduced biomarker release in DMD and control hiPSC-CMs subjected to strain. Thus, the application of mechanical strain to hiPSC-CMs produces a model that reflects an in vivo injury profile, providing a platform to assess pharmacologic intervention.

Published
2024
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73. Genetic Mosaicism in Calmodulinopathy

Author

Wren, Lisa M., primary, Jiménez-Jáimez, Juan, additional, Al-Ghamdi, Saleh, additional, Al-Aama, Jumana Y., additional, Bdeir, Amnah, additional, Al-Hassnan, Zuhair N., additional, Kuan, Jyn L., additional, Foo, Roger Y., additional, Potet, Franck, additional, Johnson, Christopher N., additional, Aziz, Miriam C., additional, Carvill, Gemma L., additional, Kaski, Juan-Pablo, additional, Crotti, Lia, additional, Perin, Francesca, additional, Monserrat, Lorenzo, additional, Burridge, Paul W., additional, Schwartz, Peter J., additional, Chazin, Walter J., additional, Bhuiyan, Zahurul A., additional, and George, Alfred L., additional

Published
2019
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74. Negligible-Cost and Weekend-Free Chemically Defined Human iPSC Culture

Author

Kuo, Hui-Hsuan, primary, Gao, Xiaozhi, additional, DeKeyser, Jean-Marc, additional, Fetterman, K. Ashley, additional, Pinheiro, Emily A., additional, Weddle, Carly J., additional, Fonoudi, Hananeh, additional, Orman, Michael V., additional, Romero-Tejeda, Marisol, additional, Jouni, Mariam, additional, Blancard, Malorie, additional, Magdy, Tarek, additional, Epting, Conrad L., additional, George, Alfred L., additional, and Burridge, Paul W., additional

Published
2019
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79. Stage-specific Effects of Bioactive Lipids on Human iPSC Cardiac Differentiation and Cardiomyocyte Proliferation

Author

Sharma, Arun, Zhang, Yuan, Buikema, Jan W., Serpooshan, Vahid, Chirikian, Orlando, Kosaric, Nina, Churko, Jared M., Dzilic, Elda, Shieh, Alice, Burridge, Paul W., Wu, Joseph C., Wu, Sean M., Sharma, Arun, Zhang, Yuan, Buikema, Jan W., Serpooshan, Vahid, Chirikian, Orlando, Kosaric, Nina, Churko, Jared M., Dzilic, Elda, Shieh, Alice, Burridge, Paul W., Wu, Joseph C., and Wu, Sean M.

Published
2018

80. Stage-specific Effects of Bioactive Lipids on Human iPSC Cardiac Differentiation and Cardiomyocyte Proliferation

Author

Cardiovasculaire Immunologie, Circulatory Health, Sharma, Arun, Zhang, Yuan, Buikema, Jan W., Serpooshan, Vahid, Chirikian, Orlando, Kosaric, Nina, Churko, Jared M., Dzilic, Elda, Shieh, Alice, Burridge, Paul W., Wu, Joseph C., Wu, Sean M., Cardiovasculaire Immunologie, Circulatory Health, Sharma, Arun, Zhang, Yuan, Buikema, Jan W., Serpooshan, Vahid, Chirikian, Orlando, Kosaric, Nina, Churko, Jared M., Dzilic, Elda, Shieh, Alice, Burridge, Paul W., Wu, Joseph C., and Wu, Sean M.

Published
2018

83. Stage-specific Effects of Bioactive Lipids on Human iPSC Cardiac Differentiation and Cardiomyocyte Proliferation

Author

Sharma, Arun, primary, Zhang, Yuan, additional, Buikema, Jan W., additional, Serpooshan, Vahid, additional, Chirikian, Orlando, additional, Kosaric, Nina, additional, Churko, Jared M., additional, Dzilic, Elda, additional, Shieh, Alice, additional, Burridge, Paul W., additional, Wu, Joseph C., additional, and Wu, Sean M., additional

Published
2018
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84. Doxorubicin induces caspase-mediated proteolysis of KV7.1

Author

Strigli, Anne, primary, Raab, Christian, additional, Hessler, Sabine, additional, Huth, Tobias, additional, Schuldt, Adam J. T., additional, Alzheimer, Christian, additional, Friedrich, Thomas, additional, Burridge, Paul W., additional, Luedde, Mark, additional, and Schwake, Michael, additional

Published
2018
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87. Passive Stretch Induces Structural and Functional Maturation of Engineered Heart Muscle as Predicted by Computational Modeling

Author

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

Published
2017
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91. Genetic Mosaicism in Calmodulinopathy.

Author

Wren, Lisa M., Jiménez-Jáimez, Juan, Al-Ghamdi, Saleh, Al-Aama, Jumana Y., Bdeir, Amnah, Al-Hassnan, Zuhair N., Kuan, Jyn L., Foo, Roger Y., Potet, Franck, Johnson, Christopher N., Aziz, Miriam C., Carvill, Gemma L., Kaski, Juan-Pablo, Crotti, Lia, Perin, Francesca, Monserrat, Lorenzo, Burridge, Paul W., Schwartz, Peter J., Chazin, Walter J., and Bhuiyan, Zahurul A.

Abstract

Supplemental Digital Content is available in the text. Background: CaM (calmodulin) mutations are associated with congenital arrhythmia susceptibility (calmodulinopathy) and are most often de novo. In this report, we sought to broaden the genotype-phenotype spectrum of calmodulinopathies with 2 novel calmodulin mutations and to investigate mosaicism in 2 affected families. Methods: CaM mutations were identified in 4 independent cases by DNA sequencing. Biochemical and electrophysiological studies were performed to determine functional consequences of each mutation. Results: Genetic studies identified 2 novel CaM variants (CALM3 -E141K in 2 cases; CALM1 -E141V) and one previously reported CaM pathogenic variant (CALM3 -D130G) among 4 probands with shared clinical features of prolonged QTc interval (range 505–725 ms) and documented ventricular arrhythmia. A fatal outcome occurred for 2 of the cases. The parents of all probands were asymptomatic with normal QTc duration. However, 2 of the families had multiple affected offspring or multiple occurrences of intrauterine fetal demise. The mother from the family with recurrent intrauterine fetal demise exhibited the CALM3 -E141K mutant allele in 25% of next-generation sequencing reads indicating somatic mosaicism, whereas CALM3 -D130G was present in 6% of captured molecules of the paternal DNA sample, also indicating mosaicism. Two novel mutations (E141K and E141V) impaired Ca2+ binding affinity to the C-domain of CaM. Human-induced pluripotent stem cell-derived cardiomyocytes overexpressing mutant or wild-type CaM showed that both mutants impaired Ca2+-dependent inactivation of L-type Ca2+ channels and prolonged action potential duration. Conclusions: We report 2 families with somatic mosaicism associated with arrhythmogenic calmodulinopathy, and demonstrate dysregulation of L-type Ca2+ channels by 2 novel CaM mutations affecting the same residue. Parental mosaicism should be suspected in families with unexplained fetal arrhythmia or fetal demise combined with a documented CaM mutation. [ABSTRACT FROM AUTHOR]

Published
2019
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92. Multi-cellular interactions sustain long-term contractility of human pluripotent stem cell-derived cardiomyocytes

Author

Burridge, Paul W, Metzler, Scott A, Nakayama, Karina H, Abilez, Oscar J, Simmons, Chelsey S, Bruce, Marc A, Matsuura, Yuka, Kim, Paul, Wu, Joseph C, Butte, Manish, Huang, Ngan F, and Yang, Phillip C

Subjects
Original Article
Abstract

Therapeutic delivery of cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) represents a novel clinical approach to regenerate the injured myocardium. However, poor survival and contractility of these cells are a significant bottleneck to their clinical use. To better understand the role of cell-cell communication in enhancing the phenotype and contractile properties of hPSC-CMs, we developed a three-dimensional (3D) hydrogel composed of hPSC-CMs, human pluripotent stem cell-derived endothelial cells (hPSC-ECs), and/or human amniotic mesenchymal stem cells (hAMSCs). The objective of this study was to examine the role of multi-cellular interactions among hPSC-ECs and hAMSCs on the survival and long-term contractile phenotype of hPSC-CMs in a 3D hydrogel. Quantification of spontaneous contractility of hPSC-CMs in tri-culture demonstrated a 6-fold increase in the area of contractile motion after 6 weeks with characteristic rhythmic contraction frequency, when compared to hPSC-CMs alone (P < 0.05). This finding was supported by a statistically significant increase in cardiac troponin T protein expression in the tri-culture hydrogel construct at 6 weeks, when compared to hPSC-CMs alone (P < 0.001). The sustained hPSC-CM survival and contractility in tri-culture was associated with a significant upregulation in the gene expression of L-type Ca2+ ion channel, Cav1.2, and the inward-rectifier potassium channel, Kir2.1 (P < 0.05), suggesting a role of ion channels in mediating these processes. These findings demonstrate that multi-cellular interactions modulate hPSC-CM phenotype, function, and survival, and they will have important implications in engineering cardiac tissues for treatment of cardiovascular diseases.

Published
2014

93. Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro

Author

Matsa, Elena, primary, Burridge, Paul W., additional, Yu, Kun-Hsing, additional, Ahrens, John H., additional, Termglinchan, Vittavat, additional, Wu, Haodi, additional, Liu, Chun, additional, Shukla, Praveen, additional, Sayed, Nazish, additional, Churko, Jared M., additional, Shao, Ningyi, additional, Woo, Nicole A., additional, Chao, Alexander S., additional, Gold, Joseph D., additional, Karakikes, Ioannis, additional, Snyder, Michael P., additional, and Wu, Joseph C., additional

Published
2016
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94. Abstract 289: Transcriptomic Analysis of Inter- and Intra-patient Variation in Human iPSCs: Platform for Precision Medicine to Predict Drug Toxicity

Author

Matsa, Elena, primary, Burridge, Paul W, additional, Yu, Kun-Hsing, additional, Wu, Haodi, additional, Termglinchan, Vittavat, additional, Liu, Chun, additional, Shukla, Praveen, additional, Sayed, Nazish, additional, Karakikes, Ioannis, additional, Snyder, Michael P, additional, and Wu, Joseph C, additional

Published
2016
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95. Screening Adverse Drug-Induced Arrhythmia Events Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Low-Impedance Microelectrode Arrays

Author

Navarrete, Enrique G., Liang, Ping, Lan, Feng, Sanchez-Freire, Verónica, Simmons, Chelsey, Gong, Tingyu, Sharma, Arun, Burridge, Paul W., Patlolla, Bhagat, Lee, Andrew S, Wu, Haodi, Beygui, Ramin E., Wu, Sean M., Robbins, Robert C., Bers, Donald M., and Wu, Joseph C.

Subjects
Male, Adolescent, Induced Pluripotent Stem Cells, Drug Evaluation, Preclinical, Action Potentials, Arrhythmias, Cardiac, Cardiovascular Agents, Article, Tissue Array Analysis, Electric Impedance, Humans, Myocytes, Cardiac, Microelectrodes, Cells, Cultured
Abstract

Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities.Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell-derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls.We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.

Published
2013

100. Induced Pluripotent Stem Cells from Familial Alzheimer's Disease Patients Differentiate into Mature Neurons with Amyloidogenic Properties

Author

Mahairaki, Vasiliki, primary, Ryu, Jiwon, additional, Peters, Ann, additional, Chang, Qing, additional, Li, Tong, additional, Park, Tea Soon, additional, Burridge, Paul W., additional, Talbot, Conover C., additional, Asnaghi, Laura, additional, Martin, Lee J., additional, Zambidis, Elias T., additional, and Koliatsos, Vassilis E., additional

Published
2014
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