Department:
Medicine-Cardiology
Research Interests
Our laboratory develops mass spectrometry and computational techniques to understand the mechanisms driving disease progression in humans. Our current research focuses include protein dynamics, protein alternative isoform, and protein annotation methods.
ER STRESS IN CARDIAC REMODELING
The integrity of cellular proteins must be constantly regulated to maintain cellular functions. Endoplasmic reticulum (ER) stress occurs when protein homeostasis is disrupted, and induces potent response pathways to restore protein folding and homeostasis. Evidence now implicates ER stress as a central feature in diseases including cardiac hypertrophy and failure, but details of how ER stress quantitatively impacts on protein expression, dynamics, and signaling are poorly understood. Our laboratory employs multidimensional proteomics techniques to define the global proteostatic landscape of the cardiac proteome and how they are dysregulated during ER stress in diseases.
DIFFERENTIAL ALTERNATIV?E ISOFORM IN THE CARDIAC PROTEOME
Alternative splicing allows eukaryotes to produce a diverse proteome from a genome of limited size, by enabling multiple protein isoforms to be encoded in a single gene. Differential expression of alternative isoforms is common in human diseases from cancer to heart failure. Current knowledge remains poor on the functional consequences of alternative protein isoforms. Our goal is to develop new multi-omics strategies by integrating RNA-seq and shotgun proteomics approaches to determine the differential expression in the cardiac proteome.
Publications
- Srivastava H, Lippincott MJ, Currie J, Canfield R, Lam MPY, Lau E. Protein prediction models support widespread post-transcriptional regulation of protein abundance by interacting partners. PLoS Comput Biol. 2022 Nov;18(11):e1010702. PubMed PMID: 36356032
- Eaton DM, Berretta RM, Lynch JE, Travers JG, Pfeiffer RD, Hulke ML, Zhao H, Hobby ARH, Schena G, Johnson JP, Wallner M, Lau E, Lam MPY, Woulfe KC, Tucker NR, McKinsey TA, Wolfson MR, Houser SR. Sex-specific responses to slow progressive pressure overload in a large animal model of HFpEF. Am J Physiol Heart Circ Physiol. 2022 Oct 1;323(4):H797-H817. PubMed PMID: 36053749
- Han Y, Wennersten SA, Wright JM, Ludwig RW, Lau E, Lam MPY. Proteogenomics reveals sex-biased aging genes and coordinated splicing in cardiac aging. Am J Physiol Heart Circ Physiol. 2022 Sep 1;323(3):H538-H558. PubMed PMID: 35930447
- Lin YH, Major JL, Liebner T, Hourani Z, Travers JG, Wennersten SA, Haefner KR, Cavasin MA, Wilson CE, Jeong MY, Han Y, Gotthardt M, Ferguson SK, Ambardekar AV, Lam MP, Choudhary C, Granzier HL, Woulfe KC, McKinsey TA. HDAC6 modulates myofibril stiffness and diastolic function of the heart. J Clin Invest. 2022 May 16;132(10). PubMed PMID: 35575093
- Han EY, Wright J, Wood SD, Lau E, Lam MP. Computation-assisted targeted proteomics of alternative splice proteins in the human heart. J Mol Cell Cardiol. 2021
- Han Y, Thomas CT, Wennersten SA, Lau E, Lam MPY. Shotgun Proteomics Sample Processing Automated by an Open-Source Lab Robot. J Vis Exp. 2021 Oct 28;(176). PubMed PMID: 34779440
- Han Y, Li LZ, Kastury NL, Thomas CT, Lam MPY, Lau E. Transcriptome features of striated muscle aging and predictability of protein level changes. Mol Omics. 2021 Oct 11;17(5):796-808. PubMed PMID: 34328155
- Chour T, Tian L, Lau E, Thomas D, Itzhaki I, Malak O, Zhang JZ, Qin X, Wardak M, Liu Y, Chandy M, Black KE, Lam MP, Neofytou E, Wu JC. Method for selective ablation of undifferentiated human pluripotent stem cell populations for cell-based therapies. JCI Insight. 2021 Apr 8;6(7). PubMed PMID: 33830086
- Travers JG, Wennersten SA, Peña B, Bagchi RA, Smith HE, Hirsch RA, Vanderlinden LA, Lin YH, Dobrinskikh E, Demos-Davies KM, Cavasin MA, Mestroni L, Steinkühler C, Lin CY, Houser SR, Woulfe KC, Lam MPY, McKinsey TA. HDAC Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling. Circulation. 2021 May 11;143(19):1874-1890. PubMed PMID: 33682427
- Han Y, Wood SD, Wright JM, Dostal V, Lau E, Lam MPY. Computation-assisted targeted proteomics of alternative splicing protein isoforms in the human heart. J Mol Cell Cardiol. 2021 May;154:92-96. PubMed PMID: 33549679
- Han Y, Wright JM, Lau E, Lam MPY. Determining Alternative Protein Isoform Expression Using RNA Sequencing and Mass Spectrometry. STAR Protoc. 2020 Dec 18;1(3):100138. PubMed PMID: 33377032
- Dostal V, Wood SD, Thomas CT, Han Y, Lau E, Lam MPY. Proteomic signatures of acute oxidative stress response to paraquat in the mouse heart. Sci Rep. 2020 Oct 28;10(1):18440. PubMed PMID: 33116222
- Adhikari S, Nice EC, Deutsch EW, Lane L, Omenn GS, Pennington SR, Paik YK, Overall CM, Corrales FJ, Cristea IM, Van Eyk JE, Uhlén M, Lindskog C, Chan DW, Bairoch A, Waddington JC, Justice JL, LaBaer J, Rodriguez H, He F, Kostrzewa M, Ping P, Gundry RL, Stewart P, Srivastava S, Srivastava S, Nogueira FCS, Domont GB, Vandenbrouck Y, Lam MPY, Wennersten S, Vizcaino JA, Wilkins M, Schwenk JM, Lundberg E, Bandeira N, Marko-Varga G, Weintraub ST, Pineau C, Kusebauch U, Moritz RL, Ahn SB, Palmblad M, Snyder MP, Aebersold R, Baker MS. A high-stringency blueprint of the human proteome. Nat Commun. 2020 Oct 16;11(1):5301. PubMed PMID: 33067450
- Lau E, Han Y, Williams DR, Thomas CT, Shrestha R, Wu JC, Lam MPY. Splice-Junction-Based Mapping of Alternative Isoforms in the Human Proteome. Cell Rep. 2019 Dec 10;29(11):3751-3765.e5. PubMed PMID: 31825849
- Han Y, Wennersten SA, Lam MPY. Working the literature harder: what can text mining and bibliometric analysis reveal?. Expert Rev Proteomics. 2019 Nov - Dec;16(11-12):871-873. PubMed PMID: 31822126
- Stratton MS, Bagchi RA, Felisbino MB, Hirsch RA, Smith HE, Riching AS, Enyart BY, Koch KA, Cavasin MA, Alexanian M, Song K, Qi J, Lemieux ME, Srivastava D, Lam MPY, Haldar SM, Lin CY, McKinsey TA. Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation. Circ Res. 2019 Sep 13;125(7):662-677. PubMed PMID: 31409188
- Lau E, Venkatraman V, Thomas CT, Wu JC, Van Eyk JE, Lam MPY. Identifying High-Priority Proteins Across the Human Diseasome Using Semantic Similarity. J Proteome Res. 2018 Dec 7;17(12):4267-4278. PubMed PMID: 30256117
- Lam MPY, Ge Y. Harnessing the Power of Proteomics to Assess Drug Safety and Guide Clinical Trials. Circulation. 2018 Mar 6;137(10):1011-1014. PubMed PMID: 29506994
- Lau E, Cao Q, Lam MPY, Wang J, Ng DCM, Bleakley BJ, Lee JM, Liem DA, Wang D, Hermjakob H, Ping P. Integrated omics dissection of proteome dynamics during cardiac remodeling. Nat Commun. 2018 Jan 9;9(1):120. PubMed PMID: 29317621
- Lam MP, Ping P, Murphy E. Proteomics Research in Cardiovascular Medicine and Biomarker Discovery. J Am Coll Cardiol. 2016 Dec 27;68(25):2819-2830. PubMed PMID: 28007144
- Lam MP, Venkatraman V, Cao Q, Wang D, Dincer TU, Lau E, Su AI, Xing Y, Ge J, Ping P, Van Eyk JE. Prioritizing Proteomics Assay Development for Clinical Translation. J Am Coll Cardiol. 2015 Jul 14;66(2):202-4. PubMed PMID: 26160638
- Lam MP, Wang D, Lau E, Liem DA, Kim AK, Ng DC, Liang X, Bleakley BJ, Liu C, Tabaraki JD, Cadeiras M, Wang Y, Deng MC, Ping P. Protein kinetic signatures of the remodeling heart following isoproterenol stimulation. J Clin Invest. 2014 Apr;124(4):1734-44. PubMed PMID: 24614109