Imperial College London

DrPeterDiMaggio

Faculty of EngineeringDepartment of Chemical Engineering

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 5589p.dimaggio Website

 
 
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Location

 

218ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

55 results found

Whitwell H, DiMaggio P, HighLight-PTM: An Online Application to aid Matching Peptide Pairs with Isotopically Labelled PTMs, Bioinformatics, ISSN: 1367-4803

Journal article

Kalesh K, Lukauskas S, Borg AJ, Snijders AP, Ayyappan V, Leung AKL, Haskard DO, DiMaggio PAet al., 2019, An integrated chemical proteomics approach for quantitative profiling of intracellular ADP-Ribosylation, Scientific Reports, Vol: 9, ISSN: 2045-2322

ADP-ribosylation is integral to a diverse range of cellular processes such as DNA repair, chromatin regulation and RNA processing. However, proteome-wide investigation of its cellular functions has been limited due to numerous technical challenges including the complexity of the poly(ADP-ribose) (PAR) chains, low abundance of the modification and lack of sensitive enrichment methods. We herein show that an adenosine analogue with a terminal alkyne functionality at position 2 of the adenine (2-alkyne adenosine or 2YnAd) is suitable for selective enrichment, fluorescence detection and mass spectrometry proteomics analysis of the candidate ADP-ribosylome in mammalian cells. Although similar labelling profiles were observed via fluorescence imaging for 2YnAd and 6YnAd, a previously reported clickable NAD+ precursor, quantitative mass spectrometry analysis of the two probes in MDA-MB-231 breast cancer cells revealed a significant increase in protein coverage of the 2YnAd probe. To facilitate global enrichment of ADP-ribosylated proteins, we developed a dual metabolic labelling approach that involves simultaneous treatment of live cells with both 2YnAd and 6YnAd. By combining this dual metabolic labelling strategy with highly sensitive tandem mass tag (TMT) isobaric mass spectrometry and hierarchical Bayesian analysis, we have quantified the responses of thousands of endogenous proteins to clinical PARP inhibitors Olaparib and Rucaparib.

Journal article

Lucia A, Dimaggio PA, 2019, A multi-scale computational approach to understanding cancer metabolism, Data Science for Healthcare: Methodologies and Applications, Pages: 327-345, ISBN: 9783030052485

© Springer Nature Switzerland AG 2019. A first principles Nash equilibrium approach to modeling, simulation, and analysis of metabolic pathways is presented. The modeling framework is described in detail, and small examples illustrating mass and charge balancing, the inclusion of enzymatic reactions in the model, constraint linear independence, and allosteric inhibition are given in order to provide a tutorial for the reader. The methodology is then applied to the methionine salvage pathway in order to demonstrate that it can correctly capture the behavior of an important pathway in the study of cancer. It is shown that methylthioadenosine (MTA) accumulation as a result of the loss of activity of the enzyme S-methyl-5′-thioadenosine phosphorylase (MTAP) is correctly predicted by the Nash equilibrium approach under tight regulation of adenine. Several examples are presented to elucidate the key ideas in modeling cancer metabolism using the Nash equilibrium approach.

Book chapter

Chavas TEJ, Fuchter MJ, DiMaggio PA, 2018, Unbiased mass spectrometry elucidation of the targets and mechanisms of activity-based probes: A case study involving sulfonyl fluorides, ACS Chemical Biology, Vol: 13, Pages: 2897-2907, ISSN: 1554-8929

The elucidation of protein/drug interactions remains a major challenge in drug discovery. Liquid chromatography–tandem mass spectrometry has emerged as a tremendously powerful technology for this endeavor, but its full potential has yet to be realized owing in part to unresolved challenges in data analysis. Herein, we demonstrate how tandem mass spectrometry can comprehensively map small molecule/peptide adducts when combined with unconstrained sequencing. Using a published sulfonyl fluoride activity-based probe as a model system, this method enabled the discovery of several unreported sites of interaction with its target proteins. Crucially, this probe was found to undergo quantitative displacement and hydrolysis from the target protein’s active site. Isotopic labeling experiments provided a mechanistic rationale for the observed hydrolysis that involves neighboring-group participation. A chemical biology tagging strategy that leverages the probe’s observed lability was developed and shown to be compatible with the original small molecule inhibitor in discovery profiling experiments.

Journal article

Lucia A, DiMaggio PA, Alonso-Martinez D, 2018, Metabolic pathway analysis using a nash equilibrium approach, JOURNAL OF GLOBAL OPTIMIZATION, Vol: 71, Pages: 537-550, ISSN: 0925-5001

Journal article

Kostrzewski T, Borg AJ, Meng Y, Filipovic I, Male V, Wack A, DiMaggio PA, Brady HJMet al., 2018, Multiple levels of control determine how E4bp4/Nfil3 regulates NK cell development, Journal of Immunology, Vol: 200, Pages: 1370-1381, ISSN: 1550-6606

The transcription factor E4bp4/Nfil3 has been shown to have a critical role in the development of all innate lymphoid cell types including NK cells. In this study, we show that posttranslational modifications of E4bp4 by either SUMOylation or phosphorylation have profound effects on both E4bp4 function and NK cell development. We examined the activity of E4bp4 mutants lacking posttranslational modifications and found that Notch1 was a novel E4bp4 target gene. We observed that abrogation of Notch signaling impeded NK cell production and the total lack of NK cell development from E4bp4−/− progenitors was completely rescued by short exposure to Notch peptide ligands. This work reveals both novel mechanisms in NK cell development by a transcriptional network including E4bp4 with Notch, and that E4bp4 is a central hub to process extrinsic stimuli.

Journal article

Lucia A, Thomas E, DiMaggio PA, 2018, On the Explicit Use of Enzyme-Substrate Reactions in Metabolic Pathway Analysis, 3rd International Conference on Machine Learning, Optimization, and Data Science (MOD), Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 88-99, ISSN: 0302-9743

Conference paper

Chen PB, Ding S, Zanghì G, Soulard V, DiMaggio PA, Fuchter MJ, Mecheri S, Mazier D, Scherf A, Malmquist NAet al., 2016, Plasmodium falciparum PfSET7: enzymatic characterization and cellular localization of a novel protein methyltransferase in sporozoite, liver and erythrocytic stage parasites., Scientific Reports, Vol: 6, ISSN: 2045-2322

Epigenetic control via reversible histone methylation regulates transcriptional activation throughout the malaria parasite genome, controls the repression of multi-copy virulence gene families and determines sexual stage commitment. Plasmodium falciparum encodes ten predicted SET domain-containing protein methyltransferases, six of which have been shown to be refractory to knock-out in blood stage parasites. We have expressed and purified the first recombinant malaria methyltransferase in sufficient quantities to perform a full enzymatic characterization and reveal the ill-defined PfSET7 is an AdoMet-dependent histone H3 lysine methyltransferase with highest activity towards lysines 4 and 9. Steady-state kinetics of the PfSET7 enzyme are similar to previously characterized histone methyltransferase enzymes from other organisms, however, PfSET7 displays specific protein substrate preference towards nucleosomes with pre-existing histone H3 lysine 14 acetylation. Interestingly, PfSET7 localizes to distinct cytoplasmic foci adjacent to the nucleus in erythrocytic and liver stage parasites, and throughout the cytoplasm in salivary gland sporozoites. Characterized recombinant PfSET7 now allows for target based inhibitor discovery. Specific PfSET7 inhibitors can aid in further investigating the biological role of this specific methyltransferase in transmission, hepatic and blood stage parasites, and may ultimately lead to the development of suitable antimalarial drug candidates against this novel class of essential parasite enzymes.

Journal article

Lucia A, Dimaggio PA, 2016, A Nash Equilibrium approach to metabolic network analysis, Pages: 45-58, ISSN: 0302-9743

© Springer International Publishing AG 2016. A novel approach to metabolic network analysis using a Nash Equilibrium formulation is proposed. Enzymes are considered to be players in a multi-player game in which each player attempts to minimize the dimensionless Gibbs free energy associated with the biochemical reaction(s) it catalyzes subject to elemental mass balances. Mathematical formulation of the metabolic network as a set of nonlinear programming (NLP) sub-problems and appropriate solution methodologies are described. A small example representing part of the production cycle for acetyl-CoA is used to demonstrate the efficacy of the proposed Nash Equilibrium framework and show that it represents a paradigm shift in metabolic network analysis.

Conference paper

Brownstein NC, Guan X, Mao Y, Zhang Q, DiMaggio PA, Xia Q, Zhang L, Marshall AG, Young NLet al., 2015, Paired single residue-transposed Lys-N and Lys-C digestions for label-free identification of N-terminal and C-terminal MS/MS peptide product ions: ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry for peptide de novo sequencing, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Vol: 29, Pages: 659-666, ISSN: 0951-4198

Journal article

Dattani R, Gibson KF, Few S, Borg AJ, DiMaggio PA, Nelson J, Kazarian SG, Cabral JTet al., 2015, Fullerene oxidation and clustering in solution induced by light, Journal of Colloid and Interface Science, Vol: 446, Pages: 24-30, ISSN: 1095-7103

We investigate the environmental stability of fullerene solutions by static and dynamic light scattering, FTIR, NMR and mass spectroscopies, and quantum chemical calculations. We find that visible light exposure of fullerene solutions in toluene, a good solvent, under ambient laboratory conditions results in C60 oxidation to form fullerene epoxides, and subsequently causes fullerene clustering in solution. The clusters grow with time, even in absence of further illumination, and can reach dimensions from ≈100 nm to the μm scale over ≈1 day. Static light scattering suggests that resulting aggregates are fractal, with a characteristic power law (df) that increases from approximately 1.3 to 2.0 during light exposure. The clusters are bound by weak Coulombic interactions and are found to be reversible, disintegrating by mechanical agitation and thermal stress, and reforming over time. Our findings are relevant to the solution processing of composites and organic photovoltaics, whose reproducibility and performance requires control of fullerene solution stability under storage conditions.

Journal article

O'Connor CM, DiMaggio PA, Shenk T, Garcia BAet al., 2014, Quantitative Proteomic Discovery of Dynamic Epigenome Changes that Control Human Cytomegalovirus (HCMV) Infection, MOLECULAR & CELLULAR PROTEOMICS, Vol: 13, Pages: 2399-2410, ISSN: 1535-9476

Journal article

Horejs C-M, Serio A, Purvis A, Gormley AJ, Bertazzo S, Poliniewicz A, Wang AJ, DiMaggio P, Hohenester E, Stevens MMet al., 2014, Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells, Proceedings of the National Academy of Sciences, Vol: 111, Pages: 5908-5913, ISSN: 1091-6490

The dynamic interplay between the extracellular matrix and embryonic stem cells (ESCs) constitutes one of the key steps in understanding stem cell differentiation in vitro. Here we report a biologically-active laminin-111 fragment generated by matrix metalloproteinase 2 (MMP2) processing, which is highly up-regulated during differentiation. We show that the β1-chain–derived fragment interacts via α3β1-integrins, thereby triggering the down-regulation of MMP2 in mouse and human ESCs. Additionally, the expression of MMP9 and E-cadherin is up-regulated in mouse ESCs—key players in the epithelial-to-mesenchymal transition. We also demonstrate that the fragment acts through the α3β1-integrin/extracellular matrix metalloproteinase inducer complex. This study reveals a previously unidentified role of laminin-111 in early stem cell differentiation that goes far beyond basement membrane assembly and a mechanism by which an MMP2-cleaved laminin fragment regulates the expression of E-cadherin, MMP2, and MMP9.

Journal article

Cherblanc FL, Chapman KL, Reid J, Borg AJ, Sundriyal S, Alcazar-Fuoli L, Bignell E, Demetriades M, Schofield CJ, DiMaggio PA, Brown R, Fuchter MJet al., 2013, On the Histone Lysine Methyltransferase Activity of Fungal Metabolite Chaetocin, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 56, Pages: 8616-8625, ISSN: 0022-2623

Journal article

LeRoy G, DiMaggio PA, Chan EY, Zee BM, Blanco MA, Bryant B, Flaniken IZ, Liu S, Kang Y, Trojer P, Garcia BAet al., 2013, A quantitative atlas of histone modification signatures from human cancer cells, EPIGENETICS & CHROMATIN, Vol: 6, ISSN: 1756-8935

Journal article

Bartke T, Borgel J, DiMaggio PA, 2013, Proteomics in epigenetics: new perspectives for cancer research, BRIEFINGS IN FUNCTIONAL GENOMICS, Vol: 12, Pages: 205-218, ISSN: 2041-2649

Journal article

Evertts AG, Zee BM, DiMaggio PA, Gonzales-Cope M, Coller HA, Garcia BAet al., 2013, Quantitative Dynamics of the Link between Cellular Metabolism and Histone Acetylation, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 288, Pages: 12142-12151

Journal article

Wu Y, DiMaggio PA, Perlman DH, Zakian VA, Garcia BAet al., 2013, Novel Phosphorylation Sites in the S. cerevisiae Cdc13 Protein Reveal New Targets for Telomere Length Regulation, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 316-327, ISSN: 1535-3893

Journal article

DiMaggio PA, Subramani A, Floudas CA, 2012, Novel biclustering methods for re-ordering data matrices, Fields Institute Communications, Vol: 63, Pages: 1-39, ISSN: 1069-5265

Clustering of large-scale data sets is an important technique that is used for analysis in a variety of fields. However, a number of these methods are based on heuristics for the identification of the best arrangement of data points. In this chapter, we present rigorous clustering methods based on the iterative optimal re-ordering of data matrices. Distinct Mixed-integer linear programming (MILP) models have been implemented to carry out clustering of dense data matrices (such as gene expression data) and sparse data matrices (such as drug discovery and toxicology).We present the capability of the optimal re-orderingmethods on a wide array of data sets from systems biology, molecular discovery and toxicology. © Springer Science+Business Media New York 2012.

Journal article

Baliban RC, DiMaggio PA, Plazas-Mayorca MD, Garcia BA, Floudas CAet al., 2012, PILOT_PROTEIN: Identification of Unmodified and Modified Proteins via High-Resolution Mass Spectrometry and Mixed-Integer Linear Optimization, JOURNAL OF PROTEOME RESEARCH, Vol: 11, Pages: 4615-4629, ISSN: 1535-3893

Journal article

Yu Y, Song C, Zhang Q, DiMaggio PA, Garcia BA, York A, Carey MF, Grunstein Met al., 2012, Histone H3 Lysine 56 Methylation Regulates DNA Replication through Its Interaction with PCNA, MOLECULAR CELL, Vol: 46, Pages: 7-17, ISSN: 1097-2765

Journal article

Baliban RC, Sakellari D, Li Z, DiMaggio PA, Garcia BA, Floudas CAet al., 2012, Novel protein identification methods for biomarker discovery via a proteomic analysis of periodontally healthy and diseased gingival crevicular fluid samples, JOURNAL OF CLINICAL PERIODONTOLOGY, Vol: 39, Pages: 203-212, ISSN: 0303-6979

Journal article

LeRoy G, Chepelev I, DiMaggio PA, Blanco MA, Zee BM, Zhao K, Garcia BAet al., 2012, Proteogenomic characterization and mapping of nucleosomes decoded by Brd and HP1 proteins, GENOME BIOLOGY, Vol: 13, ISSN: 1474-760X

Journal article

Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, DiMaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang S-C, Chen X, Chau I, Mangano TJ, Huang X-P, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin Jet al., 2011, A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells, NATURE CHEMICAL BIOLOGY, Vol: 7, Pages: 566-574, ISSN: 1552-4450

Journal article

Baliban R, DiMaggio PA, Li Z, Plazas-Mayorca M, Garcia BA, Floudas CAet al., 2011, Pilot-Protein: A high-throughput method for in silico discovery of peptides, proteins, and post-translational modifications, Pages: 124-125

Conference paper

DiMaggio PA, Young NL, Garcia BA, 2011, A multi-dimensional approach for comprehensive LC-MS/MS identification and quantitation of highly-modified protein systems, Pages: 126-127

Conference paper

Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin Jet al., 2011, Erratum: A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells (Nature Chemical Biology (2011) 7 (401-404)), Nature Chemical Biology, Vol: 7, ISSN: 1552-4450

Journal article

Zee BM, Levin RS, DiMaggio PA, Garcia BAet al., 2010, Global turnover of histone post-translational modifications and variants in human cells, EPIGENETICS & CHROMATIN, Vol: 3, ISSN: 1756-8935

Journal article

Young NL, DiMaggio PA, Garcia BA, 2010, The significance, development and progress of high-throughput combinatorial histone code analysis, CELLULAR AND MOLECULAR LIFE SCIENCES, Vol: 67, Pages: 3983-4000, ISSN: 1420-682X

Journal article

DiMaggio PA, Subramani A, Judson RS, Floudas CAet al., 2010, A Novel Framework for Predicting In Vivo Toxicities from In Vitro Data Using Optimal Methods for Dense and Sparse Matrix Reordering and Logistic Regression, TOXICOLOGICAL SCIENCES, Vol: 118, Pages: 251-265, ISSN: 1096-6080

Journal article

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