Center for Molecular Medicine Cologne

Vilchez, David - C 16

Correction of alterations in the ubiquitinated proteome to prevent age-related neurodegenerative diseases


Life expectancy has risen remarkably and the number of older people will continue to increase. Aging is a major risk factor for neurodegenerative diseases that involve protein aggregation, such as amyotrophic lateral sclerosis (ALS), Huntington’s (HD), Parkinson’s and Alzheimer’s. We have discovered that aging induces a rewiring of the ubiquitinated proteome, whereby hundreds of proteins undergo changes in ubiquitin modifications. Given the central role of ubiquitination in cell function, a functional study of these alterations can lead to novel modifiers of aging and disease. Together, our approach that combines state-of-the-art proteomics, human iPSC-disease modelling and genetics in the model organism C. elegans can provide insights into converging strategies for preventing and/or treating different age-related neurodegenerative disorders.

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Clinical Relevance

Aging causes a progressive loss of physiological integrity, which can trigger the development of multiple pathologies that remain incurable.  As such, our ever-aging society presents a challenge from the increasing prevalence of age-related diseases. Our innovative approach will define targets to slow down aging and prevent age-related neurodegenerative diseases. Thus, our project can have important implications for multi-disease prevention and be of enormous benefit for our ever-aging society.

  • Koyuncu S, Loureiro R, Lee HJ, Wagle P, Krueger M, Vilchez D (2021). Rewiring of the ubiquitinated proteome determines ageing in C. elegans. Nature 596: 285-290. DOI: 10.1038/s41586-021-03781-z
  • Calculli G, Lee HJ, Shen K, Pham U, Herholz M, Trifunovic A, Dillin A, Vilchez D (2021). Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of C. elegans. Science Advances 7: eabg3012. DOI: 10.1126/sciadv.abg3012
  • Llamas E, Torres-Montilla S, Lee HJ, Barja MV, Schlimgen E, Dunken N, Wagle P, Werr W, Zuccaro A, Rodriguez-Concepcion M, Vilchez D (2021).The intrinsic chaperone network of Arabidopsis stem cells confers protection against proteotoxic stress. Aging Cell20: e13446. DOI: 10.1111/acel.13446
  • Fatima A, Irmak D, Noormohammadi A, Rinschen MM, Das A, Leidecker O, Schindler C, Sánchez-Gaya V, Wagle P, Pokrzywa W, Hoppe T, Rada-Iglesias A, Vilchez D (2020). The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells. Communications Biology3:262. DOI: 10.1038/s42003-020-0984-3
  • Lee HJ, Noormohammadi A, Koyuncu S, Calculli G, Simic MS, Herholz M, Trifunovic A, Vilchez D (2019). Prostaglandin signals from adult germline stem cells delay somatic ageing of Caenorhabditis elegans. Nature Metabolism 1: 790-810 (cover). DOI: 10.1038/s42255-019-0097-9.
  • Koyuncu S, Saez I, Lee HJ, Gutierrez-Garcia R, Pokrzywa W, Fatima A, Hoppe T, Vilchez D (2018). The ubiquitin ligase UBR5 suppresses proteostasis collapse in immortal pluripotent stem cells from Huntington’s disease patients. Nature Communications9:2886. DOI: 10.1038/s41467-018-05320-3
  • Lee HJ, Bartsch D, Xao C, Guerrero S, Ahuja G, Schindler C, Moresco JM, Yates III JR, Gebauer F, Bazzi H, Dieterich C, Kurian L, VilchezD (2017). A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nature Communications8:1456. DOI: 10.1038/s41467-017-01744-5
  • Noormohammadi A, Khodakarami A, Gutierrez-Garcia R, Lee HJ, Koyuncu S, König T, Schindler C, Saez I, Fatima A, Dieterich C, Vilchez D (2016). Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan. Nature Communications7:13649. DOI: 10.1038/ncomms13649
  • Vilchez D, Boyer L, Morantte I, Lutz M, Merkwirth C, Joyce D, Spencer B, Page L, Masliah E, Gage FH, Dillin A (2012). Increased proteasome activity in human embryonic stem cells is regulated by PSMD11. Nature 489: 304-308. DOI: 10.1038/nature11468.
  • Vilchez D, Morantte I, Liu Z, Douglas PM, Merkwirth C, Rodrigues AP, Manning G, Dillin A (2012). RPN-6 determines C. elegans longevity under proteotoxic stress conditions. Nature 489: 263-268.
Prof. Dr. David Vilchez CMMC Cologne
Prof. Dr. David Vilchez

CECAD Research Center

CMMC - PI - C 16

+49 221 478 84172

CECAD Research Center

Joseph-Stelzmann-Str. 26

50931 Cologne

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Curriculum Vitae (CV)

Publications on PubMed

Publications - David Vilchez

Link to PubMed


Group Members

Seda Koyuncu, Hyun Ju Lee, Will Zhang
PhD students
Hafiza Alirzayeva, Saygin Bilican, Franziska Hommen, Angela Joy Johns, Markus Wehrmann
Master student
Yara Nabawi
Melissa Chmara, Nassima Salarzai