Internal route 774, Geert Grooteplein zuid 10, 6525GA Nijmegen, The Netherlands
Prof. dr. Alain J. van Gool
0031 (0)6 11783031
The Translational Metabolic Laboratory (abbreviated: TML) is a university hospital-based laboratory, part of the Department of Laboratory Medicine. TML is dedicated to discovery, validation and development of new personalized diagnostics based on metabolic biomarkers. TML’s research is focussed on Inborn Errors of Metabolism, neurodegenerative and neurometabolic diseases, iron disorders, pediatric nephrology, – infectious diseases and – oncology. The laboratory, with its 11 staff members and 100 laboratory personell, has a strong history in translational molecular medicine research with considerable scientific output (160 peer-reviewed papers annually). The laboratory hosts state-of-the-art analytical equipment (mass spectrometers, NMR) focussing on proteomics, glycomics and metabolomcis, and multiple targeted diagnostic platforms to translate research findings to patient-focussed diagnostics. TML is hosting the Radboudumc technology Center on Mass Spectrometry and is a frequent partner in service/cscientific collaborations. TML has a strong focus on functional genomics, with a long term ambition to apply its expertise to enable and accelerate personalized healthcare.
- Biomedical & health
- Translational molecular biomarker discovery, validation and diagnostics, with particular focus on implementation in personalized healthcare, for increased knowledge on molecular mechanisms of disease and for clinical diagnosis.
- Proteomics: MS-based top-down, bottom-up and targeted proteomic profiling, specialising in protein complex analysis, glycoproteomics and protein biomarker development.
- Metabolomics: untargeted and targeted metabolite analyses by LC-MS (Q-TOF, QqQ), GC-MS and targeted assays
- Glycomics: comprehensive analysis of glycans, glycopeptides and intact glycoproteins, supplemented with research into glycosylation mechanisms
- Deep analysis into genetic metabolic pathways, translating research to biomarkers to diganostics.
- Translational clinical and biochemical research to implement molecular medicine in personalized healthcare
- Inborn errors of metabolism, including congenital disorders of glycosylation.
- Mitochondrial disease, including biochemical analyses of mitochondrial proteome and protein complexes.
- Neurological disorders including Parkinson's and Alzheimer's disease.
- Pediatric nephrology, - infectious diseases and – oncology
Expertise and Track Record
40-43500-98-4162 Glycopeptide profiling of newly discovered genetic Golgi trafficking defects that affect protein glycosylation: towards identification of novel glycoproteins in hepatic steatosis and hypercholesterolemia with A.G. Holleboom (UvA). 43500984155 Nucleotide sugars in the galactosemia zebrafish model throughout development: a key step towards the development of new therapeutic strategies with A.I. Coelho (Maastricht University). 43500984145 Click to release; tracking ADC activation and ADC metabolites with H.S. Overkleeft (Leiden University). 43500984119 The goal of the project is to map and compare the mitochondrial redox proteome of mitochondrial patient- versus healthy control derived-cells maintained in standard culture conditions or exposed to a redox perturbation and/or KH176, an innovative proprietary redox-based drug developed by Khondrion. We will include the innovative Top Down proteomics approach to assess intact proteins rather than proteins fragments. The results will help to 1) identify the sites of disruption in the thiol redox circuits in mitochondrial disease, 2) decipher the effect of KH176 on the redox proteome and 3) identify new biomarkers and/or targets for mitochondrial disease drug development with J.A.M. Smeitink (Radboudumc). 43500984041 Comparative glycopeptide profiling in plasma of hypo- and hypercholesterolemic women with Jc. Wolters (UMC Groningen). 43500984004 Top-down proteomics to uncover the composition of the CCC subcomplexes and their post-translational modifications with A.J.A. van de Sluis (UMC Groningen). 435000007 Comparative proteomics and bioinformatics analysis for the identification of microRNA targets to enhance the development of miRNA-based cancer therapeutics. With dr. G.W. Verhaegh (UMC Radboud). 435002031 Advanced characterization of autoantibody profiles in rheumatoid arthritis patients with different ethnic backgrounds; searching for traces of ethnic diversity in disease development With Van der Woude (LUMC).
We offer state of the art proteomics, metabolomics and glycomics technology, which is closely connected to human genetics platforms, and which is embedded in a clinical diagnostic laboratory, facilitating smooth translation of research findings to clinical application.
- Top down proteomics: Intact protein analysis of single proteins, (affinity) purified protein complexes, and CSF/plasma/cellular proteomes using UHR Q-TOF mass spectrometry
- Clinical metabolomics: Holistic metabolomics screening by UHR Q-TOF mass spectrometry and downstream XCMS data pipelines.
- Clinical glycomics: In depth analysis of glycans and glycosylated proteins to decipher mechanisms of disease and perturbations of human biology.
- Joined experimental design in identifying mechanism of action biomarkers on proteome level with research institute partner.
- Execution of succesful pilot study with customer’s samples, followed by profiling, identification and quantification of pathway-specific biomarkers.
- Contributed to several academic studies in developing dedicated/targeted assays for metabolites.
- Elucidation of several new inborn errors of metabolism and discovery of new biomarkers by application of NMR spectroscopy
- Execution of specialized analyses and support in research design for academic and commercial partners.
- Jansen, E. J. R. et al. ATP6AP1 deficiency causes an immunodeficiency …. Nat. Commun. 7, 11600 (2016).
- Tarailo-Graovac, M. et al. Exome Sequencing and the … .N. Engl. J. Med. 374, 2246–2255 (2016).
- Van Damme, T. et al. Mutations in ATP6V1E1 or ATP6V1A …. Am. J. Hum. Genet. 100, 216–227 (2017).
- van Gool, A. J. et al. Bridging the translational innovation gap …. Nat. Rev. Drug Discov. (2017).
- van Karnebeek, C. D. M. et al. NANS-mediated synthesis of sialic acid …. Nat. Genet. 48, 777–784 (2016).
- Tegtmeyer, L. C. et al. Multiple Phenotypes in … N. Engl. J. Med. 370, 533–542 (2014).
Our group members are member of many organisations related to technologies, clinical aspects, diagnostics and diseases among which:
Netherlands: DTL (founding member), CTMM (LeARN project partner), Biomarker Development Center (founding member; Radboud UMC, Groningen University, ErasmusMC, TNO), Health-RI.
Europe: EATRIS Biomarker platform, EuropaBio Personalized Medicine Topic Group, EURO-CDG (European expertise network on genetic glycosylation disorders).
35% external parties
- Mass spectrometry: MaXis 4G ETD (UHR-QTOF MS, Bruker Daltonics), Amazon Speed ETD (Ion trap MS, Bruker Daltonics), Q-Exactive (quadrupole orbitrap MS, Thermo Fisher), TQ-S QqQ MS (Waters), Autoflex 3 (MALDI-TOF MS, Bruker Daltonics), 6540 QTOF MS (Agilent Technologies), 6490 QqQ MS (Agilent Technologies), 7890 GCMS (Agilent Technologies), QP2010 GCMS (Shimadzu), QP2010 Ultra (Shimadzu). NMR: 500 MHz Bruker Advance I. Liquid chromatography: EASY-nLC and EASY-nLC 1000 (Thermo Fisher), M-class LC (Waters), 2 nanoAdvance UHPLC (Bruker Daltonics), 2 Agilent 1260 nLC systems with nanochip cube (Agilent Technologies), 2 Agilent 1200 UHPLC (Agilent Technologies). Offline (sample enrichment/ fractionation): Acquity UHPLC (Waters).