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Christian Riedel group

Aging and age-related diseases are central to human health; we study the molecular mechanisms that regulate aging and hope to exploit them for therapeutic purposes.

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Christian Riedel

Our health and longevity is largely determined by the rate at which we age. Fortunately, aging is a plastic process. In our research group we use the nematode Caenorhabditis Elegans as a model systems to understand the pathways that can accelerate or impair aging. C. Elegans is ideal for aging-related research, as it is technically well established, short-lived (allowing for lifespan as an easily measurable phenotype), and very responsive to alterations in its aging-regulatory pathways.

These studies are complemented by efforts in human tissue culture, to verify human conservation and further explore our findings for therapeutic purposes. Our research combines biochemistry (Proteomics, ChIP-Seq, mRNA-Seq,…) with high-throughput genetic screening approaches (RNAi), to understand the regulation of aging at molecular and mechanistic resolution.

Group members

Ilke Sen

PhD, Postdoc

Lluís Millán Ariño

PhD, Postdoc

Jérôme Salignon

PhD, Postdoc

Alan Kavsek

MSc, PhD Student

Andrea Stöhr

PhD, Postdoc

Xin Zhou

PhD, Postdoc

Alumni

Lioba Körner, Master Student

Naghmeh Rajaei, Postdoc

Marco Lezzerini, Postdoc

Mengshan Liu, Master Student

Bora Baskaner, Research Assistant

Simone Brandenburg, Research Assistant

Nataly Puerta Cavanzo, Master Student

Marlies Oomen, Master Student

Irem Yücel, Bachelor Student

Tanja Iken, Bachelor Student

Georges Janssens, Postdoc

Daniel Edgar, Postdoc

Poomy Pandey, Research Assistant

Xin-Xuan Lin, PhD Student

 

Projects

The role of DAF-16/FOXO and its cofactors in aging regulation

A current focus of ours is the mechanistic exploration of aging regulatory transcription factors, in particular DAF-16/FOXO – a central driver of longevity that integrates many lifespan extending stimuli, i.e. nutrient deprivation, various stresses, or cues of infertility to confer transcription of a wide range of stress resistance and longevity determining genes. We recently identified a variety of co-factors to DAF-16/FOXO, and now we are exploring their mechanistic role.

 

The role of the chromatin landscape in aging regulation

Transcription is not only controlled by transcription factors but also the chromatin landscape that they interact with. Hence we are complementing our work by studies on the role of chromatin states, chromatin remodelers and the epigenome in the context of aging and age-related disease.

 

Search for aging-preventive interventions in humans

In addition to the mechanistic studies from above, we also seek pharmacological interventions against aging in mammalian systems, including humans. For this, we validate aging-regulatory mechanisms of particular appeal that were identified in simpler model organisms and test possible targeting strategies. Further, we develop mammalian screening methodologies that allow for the identification of aging-preventive compounds.

 

Further reading:

Janssens, G.E., Lin, X.X., Millan-Arino, L., Sen, I., Kavsek, A., Seinstra, R.I., Stroustrup, N., Nollen, E.A.A., Riedel, C.G. (2019) Transcriptomics-based screening identifies pharmacological inhibition of Hsp90 as a means to defer aging. Cell Reports 27: 467-480.

Lin, X.X., et al. (2018) DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity. Nature Communications 9(1): 4400.

Riedel, C.G. et al. (2013) DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity. Nature Cell Biology, 15, 491-501.

Kenyon, C. (2010) The genetics of ageing. Nature 464, 504-12.

Calnan, D.R. & Brunet, A. (2008) The FoxO code. Oncogene 27, 2276-88.

 

ICMC / Financial support

Christian Riedel’s group is located at and financially supported by the Integrated Cardio Metabolic Center (ICMC) at Karolinska Institutet. The ICMC has recently been established as a research collaboration between Karolinska Institutet and the pharmaceutical company AstraZeneca to address a variety of strategic research areas in the fields of cardiovascular and metabolic diseases.

In addition, the group is supported by grants from Vetenskapsrådet and Karolinska Institutet.

 

Selected publications

Transcriptomics-Based Screening Identifies Pharmacological Inhibition of Hsp90 as a Means to Defer Aging.
Janssens GE, Lin XX, Millan-Ariño L, Kavšek A, Sen I, Seinstra RI, et al
Cell Rep 2019 Apr;27(2):467-480.e6

DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity.
Lin XX, Sen I, Janssens GE, Zhou X, Fonslow BR, Edgar D, et al, Nat Commun 2018 10;9(1):4400

Regulation of Age-related Decline by Transcription Factors and Their Crosstalk with the Epigenome.
Zhou X, Sen I, Lin XX, Riedel CG
Curr. Genomics 2018 Sep;19(6):464-482

ATP-dependent chromatin remodeling: from development to disease.
Lezzerini, M., Riedel, C.G. (2016) Book Chapter in “Chromatin Regulation and Dynamics”, Elsevier, ISBN: 978-0-12-803395-1.

The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.
Heimbucher T, Liu Z, Bossard C, McCloskey R, Carrano AC, Riedel CG, et al
Cell Metab. 2015 Jul;22(1):151-63

DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.
Riedel CG, Dowen RH, Lourenco GF, Kirienko NV, Heimbucher T, West JA, et al
Nat. Cell Biol. 2013 May;15(5):491-501

The Caenorhabditis elegans RDE-10/RDE-11 complex regulates RNAi by promoting secondary siRNA amplification.
Zhang C, Montgomery TA, Fischer SE, Garcia SM, Riedel CG, Fahlgren N, et al
Curr. Biol. 2012 May;22(10):881-90

The Caenorhabditis elegans SOMI-1 zinc finger protein and SWI/SNF promote regulation of development by the mir-84 microRNA.
Hayes GD, Riedel CG, Ruvkun G
Genes Dev. 2011 Oct;25(19):2079-92

The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO.
Rizki G, Iwata TN, Li J, Riedel CG, Picard CL, Jan M, et al
PLoS Genet. 2011 Sep;7(9):e1002235

Toward the mechanisms preventing merotelic kinetochore-microtubule attachments.
Riedel CG
Cell Cycle 2010 Oct;9(20):4048-9

A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants.
Curran SP, Wu X, Riedel CG, Ruvkun G
Nature 2009 Jun;459(7250):1079-84

The kinetochore proteins Pcs1 and Mde4 and heterochromatin are required to prevent merotelic orientation.
Gregan J, Riedel CG, Pidoux AL, Katou Y, Rumpf C, Schleiffer A, et al
Curr. Biol. 2007 Jul;17(14):1190-200

Tandem affinity purification of functional TAP-tagged proteins from human cells.
Gregan J, Riedel CG, Petronczki M, Cipak L, Rumpf C, Poser I, et al
Nat Protoc 2007 ;2(5):1145-51

Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I.
Riedel CG, Katis VL, Katou Y, Mori S, Itoh T, Helmhart W, et al
Nature 2006 May;441(7089):53-61

Is chromatin remodeling required to build sister-chromatid cohesion?
Riedel CG, Gregan J, Gruber S, Nasmyth K
Trends Biochem. Sci. 2004 Aug;29(8):389-92