Center for Molecular Medicine Cologne

Kurian, Leo - A 07

Early detection and epigenetic rejuvenation strategies for age-associated cardiac dysfunctions in humans

Introduction

Loss of transcriptional control has been proposed as a causal link to cardiac ageing.

We discovered that DHS is a key molecular driver of age-associated cardiac episodes in humans by mediating the loss of transcriptional control.

A temporal decline in the functional and molecular integrity of an organism defines its ageing process. While multiple hallmarks of ageing have recently been enumerated, our understanding of their functional, molecular and temporal hierarchy remains incomplete. 

The significance of these hallmarks in the ageing process vary in a tissue/ cell type specific manner. Considering the physiological differences between organs, it is conceivable that their susceptibility to these distinct triggers of ageing can differ. 

Therefore, it is important to delineate those mechanisms that influence the ageing process of specific organs to better understand organismal ageing. We investigate evolutionarily conserved mechanisms that leads to aging of the heart.

Our Aims

We envision to 

1. develop precise molecular understanding

2. test therapeutic targets to alleviate DHS-mediated cardiotoxicity 

3. develop a preclinical serum based method for rapid, early detection of cardiac damage and ageing

For further information regarding our research please visit

Laboratory for Developmental and Regenerative RNA Biology - Dr. Leo Kurian
https://www.stammzellen.nrw.de/en/research/research-groups/laboratory-for-developmental-and-regenerative-rna-biology

  1. Frank S, Ahuja G, Bartsch D, Russ N, Yao W,  Kuo JC, Derks JP,  Akhade VS, Kargapolova Y, Georgomanolis T, Messling J, Gramm M, Brant L, Rehimi R, Vargas N E†, Kuroczik†, Yang T P, Sahito R G A, Franzen J, Hescheler J, Sachinidis A, Peifer M, Rada-Iglesias A, Kanduri M, Costa I G, Kanduri C, Papantonis A, Kurian L. yylncT defines a class of divergently-transcribed lncRNAs and safeguards the T-mediated mesodermal commitment of human PSCs. Cell Stem Cell.2019 Feb 7;24(2):318-327.e8.
  2. Ahuja G, Bartsch D, Yao W, Geissen S, Frank S, Aguirre A, Russ N, Messling J, Dodzian J, Lehmann K, Vargas N, Muck JS, Brodesser S, Baldus S, Sachinidis A, Hescheler J, Dieterich C, Trifunovic A, Papantonis A, Petrascheck M, Klinke A, Jain M, Valenzano D, Kurian L. Loss of genomic integrity by lysosphingolipid imbalance drives ageing in the heart. EMBO reports2019 Mar 18.
  3. Chao-Chung Kuo, Sonja Hanzelmann, Nevcin Sentürk, Stefan Frank, Barna Zajzon, Jens-Peter Derks, Vijay Suresh Akhade, Gaurav Ahuja, Chandrasekhar Kanduri, Ingrid Grummt, Leo Kurian, and Ivan G. Costa.  Detection of RNA–DNA binding sites in long noncoding RNAs. Nucleic Acids Research.2019 Jan 30.  
  4. Bender D, Kaczmarek AT, Santamaria-Araujoa JA, Stuevec B, Waltzc S, Bartsch D, Kurian L, Cirak S, Schwarz G. Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. Human Molecular Genetics 2019 May 25.
  5. Mondal T, Juvvuna PK, Kirkeby A, Mitra S, Kosalai ST, Traxler L, Hertwig F, Wernig-Zorc S, Miranda C, Deland L, Volland R, Bartenhagen C, Bartsch D, Bandaru S, Engesser A, Subhash S, Martinsson T, Carén H, Akyürek LM, Kurian L, Kanduri M, Huarte M, Kogner P, Fischer M, Kanduri C. Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis. Cancer Cell.2018 Mar 12;33(3):417-434.e7
  6. Kurian L, Aguirre A, Sancho-Martinez I, Benner C, Hishida T, Nguyen TB, Reddy P, Nivet E, Nelles DA, Rodriguez Esteban C, Campistol JM, Yeo GW, Izpisua Belmonte JC Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development. Circulation 2015;7;131(14):1278-90.
  • Kargapolova Y, Rehimi R, Kayserili H, Bruhl J, Sofiadis K, Zirkel A, Palikyras S, Mizi A, Li Y, Yigit G, Hoischen A, Frank S, Russ N, Trautwein J, van Bon B, Gilissen C, Laugsch M, Gusmao EG, Josipovic N, Altmuller J, Nurnberg P, Langst G, Kaiser FJ, Watrin E, Brunner H, Rada-Iglesias A, Kurian L, Wollnik B, Bouazoune K, and Papantonis A (2021). Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology. Nat Commun12, 3014. doi:10.1038/s41467-021-23327-1.
                                                                              • Mitra S, Muralidharan SV, Marco MD, Juvvuna PK, Kosalai ST, Reischl S, Jachimowicz D, Subhash S, Raimondi I, Kurian L, Huarte M, Kogner P, Fischer M, Johnsen JI, Mondal T, and Kanduri C (2021). Subcellular Distribution of p53 by the p53-Responsive lncRNA NBAT1 Determines Chemotherapeutic Response in Neuroblastoma. Cancer Res81, 1457-1471. doi:10.1158/0008-5472.CAN-19-3499.
                                                                              • Mitra S, Muralidharan SV, Di Marco M, Juvvuna PK, Kosalai ST, Reischl S, Jachimowicz D, Subhash S, Raimondi I, Kurian L, Huarte M, Kogner P, Fischer F, Johnsen JI,  Mondal T, Kanduri C: A p53 responsive lncRNA NBAT1 determines chemotherapeutic response in neuroblastoma through regulating p53 sub-cellular distribution. Cancer Research 2020 Dec 28:canres.3499.2019. doi: 10.1158/0008-5472.CAN-19-3499.
                                                                              • Laura Stanicek, Noelia Lozano-Vidal, Diewertje Ilse Bink, Aukie Hooglugt, Wenjie Yao, Ilka Wittig, Jos van Rijssel, Jaap Diederik van Buul, Anke van Bergen, Alina Klems, Anne Sophie Ramms, Ferdinand Le Noble, Patrick Hofmann, Robert Szulcek, Sheng Peng Wang, Stefan Offermanns, Meryem Seda Arslanoglu, Hyouk-Bum Kwon, Didier Stainier, Stephan Huveneers, Leo Kurian, Stefanie Dimmeler, Reinier Abraham Boon: Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function. Commun Biol . 2020 May 26;3(1):265. doi: 10.1038/s42003-020-0987-0.
                                                                              • Ahuja, G., Bartsch, D., Yao, W., Geissen, S., Frank, S., Aguirre, A., Russ, N., Messling, J.E., Dodzian, J., Lagerborg, K.A., Vargas, N.E., Muck, J.S., Brodesser, S., Baldus, S., Sachinidis, A., Hescheler, J., Dieterich, C., Trifunovic, A., Papantonis, A., Petrascheck, M., Klinke, A., Jain, M., Valenzano, D.R., and Kurian, L. (2019). Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart. EMBO Rep 20.
                                                                              • Bender, D., Kaczmarek, A.T., Santamaria-Araujo, J.A., Stueve, B., Waltz, S., Bartsch, D., Kurian, L., Cirak, S., and Schwarz, G. (2019). Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. Hum Mol Genet10.1093/hmg/ddz109.
                                                                              • Frank, S., Ahuja, G., Bartsch, D., Russ, N., Yao, W., Kuo, J.C., Derks, J.P., Akhade, V.S., Kargapolova, Y., Georgomanolis, T., Messling, J.E., Gramm, M., Brant, L., Rehimi, R., Vargas, N.E., Kuroczik, A., Yang, T.P., Sahito, R.G.A., Franzen, J., Hescheler, J., Sachinidis, A., Peifer, M., Rada-Iglesias, A., Kanduri, M., Costa, I.G., Kanduri, C., Papantonis, A., and Kurian, L. (2019). yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs. Cell Stem Cell 24, 318-27 e8.
                                                                              • Keller T, Wengenroth L, Smorra D, Probst K, Kurian L, Kribs A, and Brachvogel B (2019). Novel DRAQ5/SYTOX(R) Blue Based Flow Cytometric Strategy to Identify and Characterize Stem Cells in Human Breast Milk. Cytometry B Clin Cytom 96, 480-9.
                                                                              • Kuo, C.C., Hanzelmann, S., Senturk Cetin, N., Frank, S., Zajzon, B., Derks, J.P., Akhade, V.S., Ahuja, G., Kanduri, C., Grummt, I., Kurian, L., and Costa, I.G. (2019). Detection of RNA-DNA binding sites in long noncoding RNAs. Nucleic Acids Res 47, e32.
                                                                              • Frank S, Ahuja G, Bartsch D, Russ N, Yao W, Kuo JC, Derks JP, Akhade VS, Kargapolova Y, Georgomanolis T, Messling JE, Gramm M, Brant L, Rehimi R, Vargas NE, Kuroczik A, Yang TP, Sahito RGA, Franzen J, Hescheler J, Sachinidis A, Peifer M, Rada-Iglesias A, Kanduri M, Costa IG, Kanduri C, Papantonis A, and Kurian L (2018). yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs. Cell Stem Cell10.1016/j.stem.2018.11.005.
                                                                              • Keller T, Wengenroth L, Smorra D, Probst K, Kurian L, Kribs A, and Brachvogel B (2018). Novel DRAQ5/SYTOX(R) Blue Based Flow Cytometric Strategy to Identify and Characterize Stem Cells in Human Breast Milk. Cytometry B Clin Cytom10.1002/cyto.b.21748.
                                                                              • Mondal T, Juvvuna PK, Kirkeby A, Mitra S, Kosalai ST, Traxler L, Hertwig F, Wernig-Zorc S, Miranda C, Deland L, Volland R, Bartenhagen C, Bartsch D, Bandaru S, Engesser A, Subhash S, Martinsson T, Caren H, Akyurek LM, Kurian L, Kanduri M, Huarte M, Kogner P, Fischer M, and Kanduri C (2018). Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis. Cancer Cell 33, 417-434 e417.
                                                                              • Palanimurugan R, Godderz D, Kurian L, and Jurgen Dohmen R (2018). Analysis of Cotranslational Polyamine Sensing During Decoding of ODC Antizyme mRNA. Methods Mol Biol 1694, 309-323.
                                                                              • Ju Lee H, Bartsch D, Xiao C, Guerrero S, Ahuja G, Schindler C, Moresco JJ, Yates JR, 3rd, Gebauer F, Bazzi H, Dieterich C, Kurian L, and Vilchez D (2017). A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat Commun 8, 1456.

                                                                               

                                                                              Dr. Leo Kurian CMMC Cologne
                                                                              Dr. Leo Kurian

                                                                              Center for Molecular Medicine Cologne | Institute for Neurophysiology | CMMC Research Building

                                                                              CMMC - PI - A 07

                                                                              CMMC - PI - assoc. JRG 01

                                                                              +49 221 478 89692

                                                                              Center for Molecular Medicine Cologne | Institute for Neurophysiology | CMMC Research Building

                                                                              Robert-Koch-Str. 21

                                                                              50931 Cologne

                                                                              www.kurianlab.com

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                                                                              Curriculum Vitae (CV)

                                                                              Publications on PubMed

                                                                              Publications - Leo Kurian

                                                                              Link to PubMed

                                                                              Group Members

                                                                              Aviseka Acharya, PhD student
                                                                              Deniz Bartsch, PostDoc
                                                                              Kalamkar Kaustubh, PhD student
                                                                              Arya Mesgary, PhD student
                                                                              Christoph Walter, Master student     
                                                                              David Nelles,
                                                                              visiting scientist (Tartan LLC)