News | 23.12.2022

Computational Systems Medicine and Metabolomics Junior Research Groups


Starting in Summer 2022, Jun.-Prof. Elisa Araldi and Jun.-Prof. Thierry Schmidlin joined the DIASyM research core and started their junior research groups in Computational Systems Medicine and Metabolomics. With their expertise they will complement the DIASyM research core: They will facilitate the depth analyses and integration of complex data sets including proteome, lipidome, metabolome, transcriptome, genetics and deep clinical phenotyping to unravel the molecular architecture of the heart failure (HF) syndrome.


Computational Systems Medicine Junior Research Group
The Computational Systems Medicine junior research group headed by Dr. Elisa Araldi will develop, implement and apply computational systems medicine approaches, including data-based and mechanistic approaches.
Dr. Araldi obtained her PhD in Pathobiology and Translational Medicine at the New York University under supervision of Prof. Carlos Fernandez-Hernando and Prof. Yajaira Suarez with a thesis entitled „Lanosterol modulates innate immune responses“. Dr. Araldi is an experimental molecular biologist by training, with a focus in metabolism and metabolic diseaes, and she has gained outstanding knowledge in statistics and machine learning of multi-dimensional OMICs data. Her experiences in interdisciplinary work and analysis of human cohort data are beneficial to address issues related to cardiovascular disease - specifically HF and its risk factors (e.g., type 2 diabetes mellitus and obesity). In DIASyM, she will develop and apply methods for data integration of OMICs data and systems-based biomedical research.

SELECTED PUBLICATIONS

  1. Grigolon G, Araldi E, …, Ristow M, Fischer F. Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan. Nature Communications, 2022 Jan 10;13(1):107.

  2. Araldi E, Fernandez-Fuertes M, Canfran-Duque A, Tang W, Madrigal-Matute J, Basit A, Chamorro-Jorganes A, Lasuncion MA, Wu D, Fernandez-Hernando C and Suarez Y. Lanosterol modulates innate immune responses in macrophages. Cell Reports, 2017 Jun 27;19(13):2743-2755.

  3. Aryal B, Araldi E, Rotllan N, … , Fernandez-Hernando C. ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression. Nature Communications, 2016 Jul 27;7:12313. doi: 10.1038/ncomms12313

  4. Chamorro-Jorganes A, Araldi E, Penalva LO, Sandhu D, Fernandez-Hernando C, Suarez Y. MicroRNA16 and MicroRNA-424 Regulate Cell-Autonomous Angiogenic Functions in Endothelial Cells via Targeting Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1. Arterioscler Thrombosis Vascular Biology. 2011 Nov;31(11):2595-606.

  5. Araldi E, Khatri R, Simon MC, Giaccia AJ, Schipani E. Lack of HIF-2α in limb bud mesenchyme causes only a very modest and transient delay of endochondral bone development. Nature Medicine. 2011 Jan;17(1):25-6.

Metabolomics Junior Research Group

Approximately 60% of the metabolome consists of lipids, the remaining molecules exhibit high structure and diversity and capture many metabolic networks essential for complete molecular phenotype capture and phenome annotation based on them. To unravel the interplay between proteome, lipidome and metabolome and to unlock the potential of biomarker profiling based on multi-OMICs analyses, the junior research group of Dr. Schmidlin will contribute to the scientific, clinical and translational goals of the DIASyM research core.
Dr. Thierry Schmidlin and his junior research group in „Metabolomics“ will develop and apply high-throughput workflows for mass spectrometry-based metabolomics. With a special emphasis on polar metabolites these data sets will complement the lipidomics platform of Dr. Laura Bindila.
Dr. Thierry Schmidlin performed his PhD project at Utrecht University under supervision of Prof. Maarten Altelaar and Prof. Albert Heck. His work entitled „Novel Methods and Applications of Data-Independent and Targeted Mass Spectrometry: Towards Robust Quantification of Molecular Signaling Events“. As a postdoc, he worked on multi-OMICS approaches to characterize cholestatic liver disease at IKP Stuttgart followed by a second postdoc at University of Oxford focusing on metabolite antigens and their presentation by the immune system.
Dr. Thierry Schmidlin will establish and standardize DIA-LC-MS-based workflows for metabolomics analyses. As an outcome the group will provide metabolite descriptors that will be used in collaboration with the (bio)informatics groups of the research core to develop and adapt machine learning tools as well as predictive models.

SELECTED PUBLICATIONS

  1. Heintze, T., Wilhelm, D., Schmidlin, T., et al. Effects of Diminished NADPH:cytochrome P450 Reductase in Human Hepatocytes on Lipid and Bile Acid Homeostasis. Front. Pharmacol. 2021, 12.

  2. Schmidlin, T., Altelaar, M., Effects of Electron-Transfer/Higher-Energy Collisional Dissociation (EThcD) on Phosphopeptide Analysis by Data-independent Acquisition. Int. J. Mass Spectrom. 2020, 452.

  3. Schmidlin, T., Debets, D.O., van Gelder, C.A.G.H., Stecker K.E., et al., High-Throughput Assessment of Kinome-wide Activation States. Cell. Syst. 2019, 9(4), 366-374.

  4. Schmidlin, T., Garrigues, L., Lane, C.S., Mulder, T.C., et al., Assessment of SRM, MRM3, and DIA for the targeted analysis of phosphorylation dynamics in non-small cell lung cancer. Proteomics 2016, 16, 2193-2205.

  5. Schmidlin, T., Boender, A.J., et al., Diet-induced neuropeptide expression: feasibility of quantifying extended and highly charged endogenous peptide sequences by selected reaction monitoring. Anal. Chem. 2015, 87, 9966-9973.