Maarten Altelaar – Novel MS Based Proteomics Technologies

13 Mar Maarten Altelaar – Novel MS Based Proteomics Technologies

Maarten Altelaar develops and implements novel MS based proteomics technologies to study protein regulation and cellular signaling processes. Emphasis lies on neuronal cell differentiation and cancer signaling in acquired drug resistance and immune therapy. High-throughput (phospho)proteomics complemented with top-down MS technologies are used to target proteome dynamics.

Highlighted publications

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• Smit MA1, Maddalo G2, Greig K1, Raaijmakers LM3, Possik PA1, van Breukelen B3, Cappadona S3, Heck AJ3, Altelaar AF4, Peeper DS5. ROCK1 is a potential combinatorial drug target for BRAF mutant melanoma. Mol Syst Biol. 2014 Dec 23;10:772. PMID: 25538140. [PubMed] [Read by QxMD] Treatment of BRAF mutant melanomas with specific BRAF inhibitors leads to tumor remission. However, most patients eventually relapse due to drug resistance. Therefore, we designed an integrated strategy using (phospho)proteomic and functional genomic platforms to identify drug targets whose inhibition sensitizes melanoma cells to BRAF inhibition. We found many proteins to be induced upon PLX4720 (BRAF inhibitor) treatment that are known to be inv [...]
• de Graaf EL1, Kaplon J2, Zhou H3, Heck AJ1, Peeper DS4, Altelaar AF5. Phosphoproteome dynamics in onset and maintenance of oncogene-induced senescence. Mol Cell Proteomics. 2014 Aug;13(8):2089-100. PMID: 24961811. [PubMed] [Read by QxMD] Expression of the BRAF(V600E) oncoprotein is known to cause benign lesions, such as melanocytic nevi (moles). Despite the oncogenic function of mutant BRAF, these lesions are arrested by a cell-autonomous mechanism called oncogene-induced senescence. Infrequently, nevi can progress to malignant melanoma, through mechanisms that are incompletely understood. To gain more insight into this vital tumor-suppression mechanism, we performed a mass-spect [...]
• Castaño-Cerezo S1, Bernal V2, Post H3, Fuhrer T4, Cappadona S5, Sánchez-Díaz NC1, Sauer U4, Heck AJ3, Altelaar AF3, Cánovas M2. Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli. Mol Syst Biol. 2014 Nov 27;10:762. PMID: 25518064. [PubMed] [Read by QxMD] Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identif [...]
• Frese CK1, Boender AJ, Mohammed S, Heck AJ, Adan RA, Altelaar AF. Profiling of diet-induced neuropeptide changes in rat brain by quantitative mass spectrometry. Anal Chem. 2013 May 7;85(9):4594-604. PMID: 23581470. [PubMed] [Read by QxMD] Neuropeptides are intercellular signal transmitters that play key roles in modulation of many behavioral and physiological processes. Neuropeptide signaling in several nuclei in the hypothalamus contributes to the control of food intake. Additionally, food intake regulation involves neuropeptide signaling in the reward circuitry in the striatum. Here, we analyze neuropeptides extracted from hypothalamus and striatum from rats in four differential [...]
• Ringrose JH1, van den Toorn HW, Eitel M, Post H, Neerincx P, Schierwater B, Altelaar AF, Heck AJ. Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity. Nat Commun. 2013;4:1408. PMID: 23360999. [PubMed] [Read by QxMD] Genome sequencing of arguably the simplest known animal, Trichoplax adhaerens, uncovered a rich array of transcription factor and signalling pathway genes. Although the existence of such genes allows speculation about the presence of complex regulatory events, it does not reveal the level of actual protein expression and functionalization through posttranslational modifications. Using high-resolution mass spectrometry, we here semi-quantify 6,516 [...]
• Altelaar AF1, Munoz J, Heck AJ. Next-generation proteomics: towards an integrative view of proteome dynamics. Nat Rev Genet. 2013 Jan;14(1):35-48. PMID: 23207911. [PubMed] [Read by QxMD] Next-generation sequencing allows the analysis of genomes, including those representing disease states. However, the causes of most disorders are multifactorial, and systems-level approaches, including the analysis of proteomes, are required for a more comprehensive understanding. The proteome is extremely multifaceted owing to splicing and protein modifications, and this is further amplified by the interconnectivity of proteins into complexes an [...]

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