Selected publications from our group members.

  • MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes

    S. Veitch, M. S. Njock, M. Chandy, M. A. Siraj, L. Chi, H. Mak, K. Yu, K. Rathnakumar, C. A. Perez-Romero, Z. Chen, F. J. Alibhai, D. Gustafson, S. Raju, R. Wu, D. Z. Khat, Y. Wang, A. Caballero, P. Meagher, E. Lau, L. Pepic, H. S. Cheng, N. J. Galant, K. L. Howe, R. K. Li, K. A. Connelly, M. Husain, P. Delgado-Olguin, and J. E. Fish

    Cardiovasc Diabetol, 21(1), 31, 2022
    URL RIS BibTex
  • JCAST: Sample-specific protein isoform databases for mass spectrometry-based proteomics experiments

  • JCAST is an open-source Python software tool that allows users to easily create custom protein sequence databases for proteogenomic applications. JCAST takes in RNA sequencing data containing alternative splicing junctions as input, models the likely translatable protein isoform sequences within a particular sample, performs in silico translation using annotated open reading frames, and outputs sample-specific protein sequence databases in FASTA format to support downstream mass spectrometry data analysis of protein isoforms. This article describes the functionality and usage of the JCAST software and documents a stable code repository for user access.

  • Transcriptome features of striated muscle aging and predictability of protein level changes

    Y. Han, L. Z. Li, N. L. Kastury, C. T. Thomas, M. P. Y. Lam, and E. Lau

    Mol. Omics, 2021
    URL DOI RIS BibTex
  • We performed total RNA sequencing and multi-omics analysis comparing skeletal muscle and cardiac muscle in young adult (4 months) vs. early aging (20 months) mice to examine the molecular mechanisms of striated muscle aging. We observed that aging cardiac and skeletal muscles both invoke transcriptomic changes in innate immune system and mitochondria pathways but diverge in extracellular matrix processes. On an individual gene level, we identified 611 age-associated signatures in skeletal and cardiac muscles, including a number of myokine and cardiokine encoding genes. Because RNA and protein levels correlate only partially, we reason that differentially expressed transcripts that accurately reflect their protein counterparts will be more valuable proxies for proteomic changes and by extension physiological states. We applied a computational data analysis workflow to estimate which transcriptomic changes are more likely relevant to protein-level regulation using large proteogenomics data sets. We estimate about 48% of the aging-associated transcripts predict protein levels well (r ≥ 0.5). In parallel, a comparison of the identified aging-regulated genes with public human transcriptomics data showed that only 35–45% of the identified genes show an age-dependent expression in corresponding human tissues. Thus, integrating both RNA–protein correlation and human conservation across data sources, we nominate 134 prioritized aging striated muscle signatures that are predicted to correlate strongly with protein levels and that show age-dependent expression in humans. The results here reveal new details into how aging reshapes gene expression in striated muscles at the transcript and protein levels.

  • Serum response factor deletion 5 regulates phospholamban phosphorylation and calcium uptake

    K. C. Woulfe, D. A. Jeffrey, J. P. D. Silva, C. E. Wilson, J. H. Mahaffey, E. Lau, D. Slavov, F. Hailu, A. Karimpour-Fard, K. Dockstader, M. R. Bristow, B. L. Stauffer, S. D. Miyamoto, and C. C. Sucharov

    J Mol Cell Cardiol, 159, 28-37, 2021
    RIS BibTex
  • Method for selective ablation of undifferentiated human pluripotent stem cell populations for cell-based therapies

    T. Chour, L. Tian, E. Lau, D. Thomas, I. Itzhaki, O. Malak, J. Z. Zhang, X. Qin, M. Wardak, Y. Liu, M. Chandy, K. E. Black, M. P. Lam, E. Neofytou, and J. C. Wu

    JCI Insight, 6(7), 2021
    RIS BibTex
  • Computation-assisted targeted proteomics of alternative splicing protein isoforms in the human heart

    Y. Han, S. D. Wood, J. M. Wright, V. Dostal, E. Lau, and M. P. Y. Lam

    J Mol Cell Cardiol, 154, 92-96, 2021
    URL RIS BibTex
  • Atlas of exosomal microRNAs secreted from human iPSC-derived cardiac cell types

    M. Chandy, J. W. Rhee, M. O. Ozen, D. R. Williams, L. Pepic, C. Liu, H. Zhang, J. Malisa, E. Lau, U. Demirci, and J. C. Wu

    Circulation, 142(18), 1794-1796, 2020
    URL RIS BibTex
  • Cardiac-derived exosomes have received intense interest for their roles in paracrine communications and regenerative therapies. However, current understanding of how exosomes mediate cellular signaling is incomplete, in part because the contents of exosomes from different cardiac cell types are poorly defined. To learn what signals cardiac cells release, we examined the microRNA (miRNA) compositions secreted in exosomes from human induced pluripotent stem cells (iPSCs) and 3 major iPSC-derived cardiac cell types.

  • Proteomic signatures of acute oxidative stress response to paraquat in the mouse heart

    V. Dostal, S. D. Wood, C. T. Thomas, Y. Han, E. Lau, and M. P. Y. Lam

    Sci Rep, 10(1), 18440, 2020
    RIS BibTex
  • High-throughput preparation of DNA, RNA, and protein from cryopreserved human iPSCs for multi-omics analysis

    J. X. Zhang, E. Lau, D. T. Paik, Y. Zhuge, and J. C. Wu

    Current protocols in stem cell biology, 54(1), e114, 2020
    URL DOI RIS BibTex
  • We describe the procedure to isolate genomic DNA, RNA, and protein directly from cryopreserved induced pluripotent stem cell (iPSC) vials using commercially available solid‐phase extraction kits, and we report the relationship between macromolecule yields and experimental and storage factors. Sufficient quantities of DNA, RNA, and protein are recoverable from as low as 1 million cryopreserved cells across 728 distinct iPSC lines suitable for whole‐genome sequencing, RNA sequencing, and mass spectrometry experiments. Nucleic acids extracted from iPSC stocks cryopreserved up to 4 years maintain sufficient quantity and integrity for downstream analysis with minimal genomic DNA fragmentation. An expected positive correlation exists between cell count and DNA or RNA yield, with comparable yields recovered between cells across different cryostorage timespans. This article provides an effective way to simultaneously isolate iPSC biomolecules for multi‐omics investigations.

  • Modeling secondary iron overload cardiomyopathy with human induced pluripotent stem cell-derived cardiomyocytes

    J.-W. Rhee, H. Yi, D. Thomas, C. K. Lam, N. Belbachir, L. Tian, X. Qin, J. Malisa, E. Lau, D. T. Paik, Y. Kim, B. S. Choi, N. Sayed, K. Sallam, R. Liao, and J. C. Wu

    Cell reports, 32(2), 107886, 2020
    URL DOI RIS BibTex
  • Splice-junction-based mapping of alternative isoforms in the human proteome

    E. Lau, Y. Han, D. R. Williams, C. T. Thomas, R. Shrestha, J. C. Wu, and M. P. Y. Lam

    Cell reports, 29(11), 3751—3765.e5, 2019
    URL DOI RIS BibTex
  • Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy

    J. Lee, V. Termglinchan, S. Diecke, I. Itzhaki, C. K. Lam, P. Garg, E. Lau, M. Greenhaw, T. Seeger, H. Wu, J. Z. Zhang, X. Chen, I. P. Gil, M. Ameen, K. Sallam, J.-W. Rhee, J. M. Churko, R. Chaudhary, T. Chour, P. J. Wang, M. P. Snyder, H. Y. Chang, I. Karakikes, and J. C. Wu

    Nature, 572(7769), 335—340, 2019
    URL DOI RIS BibTex
  • A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay

    T. Seeger, R. Shrestha, C. K. Lam, C. Chen, W. L. McKeithan, E. Lau, A. Wnorowski, G. McMullen, M. Greenhaw, J. Lee, A. Oikonomopoulos, S. Lee, H. Yang, M. Mercola, M. Wheeler, E. A. Ashley, F. Yang, I. Karakikes, and J. C. Wu

    Circulation, 139(6), 799—811, 2019
    URL DOI RIS BibTex
  • Systems-Wide Approaches in Induced Pluripotent Stem Cell Models

    E. Lau, D. T. Paik, and J. C. Wu

    Annual review of pathology, 14, 395—419, 2019
    URL DOI RIS BibTex
  • Human induced pluripotent stem cells (iPSCs) provide a renewable supply of patient-specific and tissue-specific cells for cellular and molecular studies of disease mechanisms. Combined with advances in various omics technologies, iPSC models can be used to profile the expression of genes, transcripts, proteins, and metabolites in relevant tissues. In the past 2 years, large panels of iPSC lines have been derived from hundreds of genetically heterogeneous individuals, further enabling genome-wide mapping to identify coexpression networks and elucidate gene regulatory networks. Here, we review recent developments in omics profiling of various molecular phenotypes and the emergence of human iPSCs as a systems biology model of human diseases.

  • Identifying high-priority proteins across the human diseasome using semantic similarity

    E. Lau, V. Venkatraman, C. T. Thomas, J. C. Wu, J. E. V. Eyk, and M. P. Y. Lam

    Journal of proteome research, 17(12), 4267—4278, 2018
    URL DOI RIS BibTex
  • Omics, big data, and precision medicine in cardiovascular sciences

    E. Lau and J. C. Wu

    Circulation research, 122(9), 1165—1168, 2018
    URL DOI RIS BibTex
  • Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix

    A. S. Lee, M. Inayathullah, M. A. Lijkwan, X. Zhao, W. Sun, S. Park, W. X. Hong, M. B. Parekh, A. V. Malkovskiy, E. Lau, X. Qin, V. R. Pothineni, V. Sanchez-Freire, W. Y. Zhang, N. G. Kooreman, A. D. Ebert, C. K. F. Chan, P. K. Nguyen, J. Rajadas, and J. C. Wu

    Nature biomedical engineering, 2(2), 104—113, 2018
    URL DOI RIS BibTex
  • NextGen VOICES: Research resolutions

    F. Olmeta-Schult, L. M. Segal, S. Tyner, T. A. Moon, R. D.-W. Chow, P. Chakrabarty, M. Pacesa, A. I. Podgornaia, J. Chen, B. Singh, B. Cao, R. R. S. Sidhu, B. W. Q. Tan, P. Sood, S. Parker, M. A. Scult, D. V. Haute, N. Konstantinides, B. A. Schwendimann, S. Srivastava, R. Fiorenza, K. Dutton-Regester, R. Hale, E. O. Polat, E. Lau, A. L. Mayer, and E. R. White

    Science (New York, N.Y.), 359(6371), 26—28, 2018
    URL DOI RIS BibTex
  • Integrated Omics Dissection of Proteome Dynamics During Cardiac Remodeling

    E. Lau, Q. Cao, M. P. Y. Lam, J. Wang, D. C. M. Ng, B. J. Bleakley, J. M. Lee, D. A. Liem, D. Wang, H. Hermjakob, and P. Ping

    Nature communications, 9(1), 120, 2018
  • Transcript abundance and protein abundance show modest correlation in many biological models, but how this impacts disease signature discovery in omics experiments is rarely explored. Here we report an integrated omics approach, incorporating measurements of transcript abundance, protein abundance, and protein turnover to map the landscape of proteome remodeling in a mouse model of pathological cardiac hypertrophy. Analyzing the hypertrophy signatures that are reproducibly discovered from each omics data type across six genetic strains of mice, we find that the integration of transcript abundance, protein abundance, and protein turnover data leads to 75% gain in discovered disease gene candidates. Moreover, the inclusion of protein turnover measurements allows discovery of post-transcriptional regulations across diverse pathways, and implicates distinct disease proteins not found in steady-state transcript and protein abundance data. Our results suggest that multi-omics investigations of proteome dynamics provide important insights into disease pathogenesis in vivo.

  • Cardiovascular proteomics in the era of big data: experimental and computational advances

    M. P. Y. Lam, E. Lau, D. C. M. Ng, D. Wang, and P. Ping

    Clinical proteomics, 13, 23, 2016
    URL DOI RIS BibTex
  • Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems

    M. P. Y. Lam, V. Venkatraman, Y. Xing, E. Lau, Q. Cao, D. C. M. Ng, A. I. Su, J. Ge, J. E. V. Eyk, and P. Ping

    Journal of proteome research, 15(11), 4126—4134, 2016
    URL DOI RIS BibTex
  • Connecting the Dots: From Big Data to Healthy Heart

    E. Lau, K. E. Watson, and P. Ping

    Circulation, 134(5), 362—364, 2016
    URL DOI RIS BibTex
  • Identifying Low-Abundance Biomarkers: Aptamer-Based Proteomics Potentially Enables More Sensitive Detection in Cardiovascular Diseases

    A. Gramolini, E. Lau, and P. P. Liu

    Circulation, 134(4), 286—289, 2016
    URL DOI RIS BibTex
  • A large dataset of protein dynamics in the mammalian heart proteome

    E. Lau, Q. Cao, D. C. M. Ng, B. J. Bleakley, T. U. Dincer, B. M. Bot, D. Wang, D. A. Liem, M. P. Y. Lam, J. Ge, and P. Ping

    Scientific data, 3, 160015, 2016
    URL DOI RIS BibTex
  • Label-Free Quantitative Proteomics Reveals Survival Mechanisms Developed by Hypertrophic Chondrocytes under ER Stress

    M. Kudelko, C. W. L. Chan, R. Sharma, Q. Yao, E. Lau, I. K. Chu, K. S. E. Cheah, J. A. Tanner, and D. Chan

    Journal of proteome research, 15(1), 86—99, 2016
    URL DOI RIS BibTex
  • Prioritizing Proteomics Assay Development for Clinical Translation

    M. P. Y. Lam, V. Venkatraman, Q. Cao, D. Wang, T. U. Dincer, E. Lau, A. I. Su, Y. Xing, J. Ge, P. Ping, and J. E. V. Eyk

    Journal of the American College of Cardiology, 66(2), 202—204, 2015
    URL DOI RIS BibTex
  • Spatial and temporal dynamics of the cardiac mitochondrial proteome

    E. Lau, D. Huang, Q. Cao, T. U. Dincer, C. M. Black, A. J. Lin, J. M. Lee, D. Wang, D. A. Liem, M. P. Y. Lam, and P. Ping

    Expert review of proteomics, 12(2), 133—146, 2015
    URL DOI RIS BibTex
  • Mitochondrial protein turnover: methods to measure turnover rates on a large scale

    X. C. Y. Chan, C. M. Black, A. J. Lin, P. Ping, and E. Lau

    Journal of molecular and cellular cardiology, 78, 54—61, 2015
    URL DOI RIS BibTex
  • Mitochondrial proteins carry out diverse cellular functions including ATP synthesis, ion homeostasis, cell death signaling, and fatty acid metabolism and biogenesis. Compromised mitochondrial quality control is implicated in various human disorders including cardiac diseases. Recently it has emerged that mitochondrial protein turnover can serve as an informative cellular parameter to characterize mitochondrial quality and uncover disease mechanisms. The turnover rate of a mitochondrial protein reflects its homeostasis and dynamics under the quality control systems acting on mitochondria at a particular cell state. This review article summarizes some recent advances and outstanding challenges for measuring the turnover rates of mitochondrial proteins in health and disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".

  • Characterization of human plasma proteome dynamics using deuterium oxide

    D. Wang, D. A. Liem, E. Lau, D. C. M. Ng, B. J. Bleakley, M. Cadeiras, M. C. Deng, M. P. Y. Lam, and P. Ping

    Proteomics. Clinical applications, 8(78), 610—619, 2014
    URL DOI RIS BibTex
  • Lysine ubiquitination and acetylation of human cardiac 20S proteasomes

    N. Zong, P. Ping, E. Lau, H. J. Choi, D. C. Ng, D. Meyer, C. Fang, H. Li, D. Wang, I. M. Zelaya, J. R. Yates, and M. P. Lam

    Proteomics. Clinical applications, 8(78), 590—594, 2014
    URL DOI RIS BibTex
  • Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

    M. P. Y. Lam, D. Wang, E. Lau, D. A. Liem, A. K. Kim, D. C. M. Ng, X. Liang, B. J. Bleakley, C. Liu, J. D. Tabaraki, M. Cadeiras, Y. Wang, M. C. Deng, and P. Ping

    The Journal of clinical investigation, 124(4), 1734—1744, 2014
    URL DOI RIS BibTex
  • Characterization, design, and function of the mitochondrial proteome: from organs to organisms

    C. Lotz, A. J. Lin, C. M. Black, J. Zhang, E. Lau, N. Deng, Y. Wang, N. C. Zong, J. H. Choi, T. Xu, D. A. Liem, P. Korge, J. N. Weiss, H. Hermjakob, J. R. Yates, R. Apweiler, and P. Ping

    Journal of proteome research, 13(2), 433—446, 2014
    URL DOI RIS BibTex
  • Cyclophilin D and acetylation: a new link in cardiac signaling

    M. P. Y. Lam, E. Lau, D. A. Liem, and P. Ping

    Circulation research, 113(12), 1268—1269, 2013
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  • Response to Pomozi et al's research commentary

    L. J. Martin, E. Lau, H. Singh, L. Vergnes, E. J. Tarling, M. Mehrabian, I. Mungrue, S. Xiao, D. Shih, L. Castellani, P. Ping, K. Reue, E. Stefani, T. A. Drake, K. Bostrom, and A. J. Lusis

    Circulation research, 112(11), e152—3, 2013
    URL DOI RIS BibTex
  • Site-specific quantitative analysis of cardiac mitochondrial protein phosphorylation

    M. P. Y. Lam, E. Lau, S. B. Scruggs, D. Wang, T.-Y. Kim, D. A. Liem, J. Zhang, C. M. Ryan, K. F. Faull, and P. Ping

    Journal of proteomics, 81, 15—23, 2013
    URL DOI RIS BibTex
  • Metabolic labeling reveals proteome dynamics of mouse mitochondria

    T.-Y. Kim, D. Wang, A. K. Kim, E. Lau, A. J. Lin, D. A. Liem, J. Zhang, N. C. Zong, M. P. Y. Lam, and P. Ping

    Molecular & cellular proteomics : MCP, 11(12), 1586—1594, 2012
    URL DOI RIS BibTex
  • An MRM-based workflow for quantifying cardiac mitochondrial protein phosphorylation in murine and human tissue

    M. P. Y. Lam, S. B. Scruggs, T.-Y. Kim, C. Zong, E. Lau, D. Wang, C. M. Ryan, K. F. Faull, and P. Ping

    Journal of proteomics, 75(15), 4602—4609, 2012
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  • ABCC6 localizes to the mitochondria-associated membrane

    L. J. Martin, E. Lau, H. Singh, L. Vergnes, E. J. Tarling, M. Mehrabian, I. Mungrue, S. Xiao, D. Shih, L. Castellani, P. Ping, K. Reue, E. Stefani, T. A. Drake, K. Bostrom, and A. J. Lusis

    Circulation research, 111(5), 516—520, 2012
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  • Perspectives on: SGP symposium on mitochondrial physiology and medicine: mitochondrial proteome design: from molecular identity to pathophysiological regulation

    J. Zhang, A. Lin, J. Powers, M. P. Lam, C. Lotz, D. Liem, E. Lau, D. Wang, N. Deng, P. Korge, N. C. Zong, H. Cai, J. Weiss, and P. Ping

    The Journal of general physiology, 139(6), 395—406, 2012
    URL DOI RIS BibTex
  • Substrate- and isoform-specific proteome stability in normal and stressed cardiac mitochondria

    E. Lau, D. Wang, J. Zhang, H. Yu, M. P. Y. Lam, X. Liang, N. Zong, T.-Y. Kim, and P. Ping

    Circulation research, 110(9), 1174—1178, 2012
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  • Online combination of reversed-phase/reversed-phase and porous graphitic carbon liquid chromatography for multicomponent separation of proteomics and glycoproteomics samples

    M. P. Y. Lam, E. Lau, S. Siu, D. C. M. Ng, R. P. W. Kong, P. C. N. Chiu, W. S. B. Yeung, C. Lo, and I. K. Chu

    Electrophoresis, 32(21), 2930—2940, 2011
    URL DOI RIS BibTex
  • Fully automatable two-dimensional reversed-phase capillary liquid chromatography with online tandem mass spectrometry for shotgun proteomics

    S. Siu, M. P. Y. Lam, E. Lau, R. P. W. Kong, S. M. Y. Lee, and I. K. Chu

    Proteomics, 11(11), 2308—2319, 2011
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  • Combinatorial use of offline SCX and online RP-RP liquid chromatography for iTRAQ-based quantitative proteomics applications

    E. Lau, M. P. Y. Lam, S. Siu, R. P. W. Kong, W. L. Chan, Z. Zhou, J. Huang, C. Lo, and I. K. Chu

    Molecular bioSystems, 7(5), 1399—1408, 2011
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  • Online coupling of reverse-phase and hydrophilic interaction liquid chromatography for protein and glycoprotein characterization

    M. P. Y. Lam, S. Siu, E. Lau, X. Mao, H. Sun, P. C. N. Chiu, W. S. B. Yeung, D. M. Cox, and I. K. Chu

    Analytical and bioanalytical chemistry, 398(2), 791—804, 2010
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  • OsNOA1/RIF1 is a functional homolog of AtNOA1/RIF1: implication for a highly conserved plant cGTPase essential for chloroplast function

    H. Liu, E. Lau, M. P. Y. Lam, H. Chu, S. Li, G. Huang, P. Guo, J. Wang, L. Jiang, I. K. Chu, C. Lo, and Y. Tao

    The New phytologist, 187(1), 83—105, 2010
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  • N-linked glycoprotein analysis using dual-extraction ultrahigh-performance liquid chromatography and electrospray tandem mass spectrometry

    S. Siu, M. P. Y. Lam, E. Lau, W. S. B. Yeung, D. M. Cox, and I. K. Chu

    Methods in molecular biology (Clifton, N.J.), 600, 133—143, 2009
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