SHEP cells

The Henssen Lab

The Henssen Lab in the Department of Pediatrics at the Charité - University Medicine Berlin is interested in deciphering the mechanisms that lead to the formation of refractory neuroblastoma and rhabdomyosarcoma.

 

 

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Research focus of the Henssen Lab

Our group of physicians and scientists in the Department of Pediatric Hematology and Oncology at the Charité University Medicine is particularly interested in understanding how refractory neuroblastoma and rhabdomyosarcoma are formed. Our research is focused on the phenomenon of genomic plasticity and its resultant therapeutically targetable vulnerabilities.

To elucidate mechanisms of genomic plasticity, we are developing functional genomics approaches using high-throughput DNA, RNA and ChIP sequencing. Our long term goal is to determine specific cancer vulnerabilities that can guide clinical trials of personalized treatments for children with refractory cancers.

Personalized therapeutic targeting of specific tumor vulnerabilities

The lab studies three of the most common cancers in pediatric patients: neuroblastoma, rhabdomyosarcoma and rhabdoid tumors. These tumors can be highly lethal and very difficult to treat.
One of the major clinical challenges in these tumors is to identify tumor specific vulnerabilities that can be inhibited by drugs, which will only affect the tumor and spare healthy tissue. The lab focuses on understanding the underlying genetic reasons/ mutations that cause tumor vulnerabilities. In order to do so, the lab focuses on recently developed high-throughput sequencing technologies to decipher the genomes of patient tumors. Most importantly, the lab is interested in cancer specific DNA structures such as transposons and circular intermediates termed “extra chromosomal circular DNA” (eccDNA). The lab studies how these structures are formed and how they contribute to the formation of pediatric cancers.
Could these cancer specific circles be used for cancer diagnostics? Could their effect on cells be blocked by therapeutics? Why do children at such a young age form DNA circles?
These are the main questions the Henssen Research Group is trying to answer.

Publications

Henssen AG, Koche R, Zhuang J, Jiang E, Reed C, Eisenberg A, Still E, MacArthur IC, Rodríguez-Fos E, Gonzalez S, Puiggròs M, Blackford AN, Mason CE, de Stanchina E, Gönen M, Emde AK, Shah M, Arora K, Reeves C, Socci ND, Perlman E, Antonescu CR, Roberts CWM, Steen H, Mullen E, Jackson SP, Torrents D, Weng Z, Armstrong SA, Kentsis A.
PGBD5 promotes site-specific oncogenic mutations in human tumors.
Nat Genet. 2017 May 15. doi: 10.1038/ng.3866. [Epub ahead of print] PubMed PMID: 28504702.

Henssen AG, Odersky A, Szymansky A, Seiler M, Althoff K, Beckers A, Speleman F, Schäfers S, De Preter K, Astrahanseff K, Struck J, Schramm A, Eggert A, Bergmann A, Schulte JH.
Targeting tachykinin receptors in neuroblastoma.
Oncotarget. 2017 Jan 3;8(1):430-443. doi: 10.18632/oncotarget.13440. PubMed PMID: 27888795

Henssen AG, Jiang E, Zhuang J, Pinello L, Socci ND, Koche R, Gonen M, Villasante CM, Armstrong SA, Bauer DE, Weng Z, Kentsis A.
Forward genetic Screen of human transposase genomic rearrangements.
BMC Genomics. 2016 Aug 4;17:548. doi: 10.1186/s12864-016-2877-x. PubMed PMID: 27491780

Henssen A, Zilles K, Palomero-Gallagher N, Schleicher A, Mohlberg H, Gerboga F, Eickhoff SB, Bludau S, Amunts K.
Cytoarchitecture and probability maps of the human medial orbitofrontal cortex.
Cortex. 2016 Feb;75:87-112. doi: 10.1016/j.cortex.2015.11.006. Epub 2015 Dec 2. PubMed PMID: 26735709.

Henssen A, Althoff K, Odersky A, Beckers A, Koche R, Speleman F, Schäfers S, Bell E, Nortmeyer M, Westermann F, De Preter K, Florin A, Heukamp L, Spruessel A, Astrahanseff K, Lindner S, Sadowski N, Schramm A, Astorgues-Xerri L, Riveiro ME,  Eggert A, Cvitkovic E, Schulte JH.
Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition.
Clin Cancer Res. 2016 May 15;22(10):2470-81. doi: 10.1158/1078-0432.CCR-15-1449. Epub 2015 Dec 2. PubMed PMID: 26631615.

Henssen AG, Henaff E, Jiang E, Eisenberg AR, Carson JR, Villasante CM, Ray M, Still E, Burns M, Gandara J, Feschotte C, Mason CE, Kentsis A.
Genomic DNA transposition induced by human PGBD5.
Elife. 2015 Sep 25;4. pii: e10565. doi: 10.7554/eLife.10565. PubMed PMID: 26406119

Schramm A, Köster J, Assenov Y, Althoff K, Peifer M, Mahlow E, Odersky A, Beisser D, Ernst C, Henssen AG, Stephan H, Schröder C, Heukamp L, Engesser A, Kahlert Y, Theissen J, Hero B, Roels F, Altmüller J, Nürnberg P, Astrahantseff K, Gloeckner C, De Preter K, Plass C, Lee S, Lode HN, Henrich KO, Gartlgruber M,
Speleman F, Schmezer P, Westermann F, Rahmann S, Fischer M, Eggert A, Schulte JH.
Mutational dynamics between primary and relapse neuroblastomas.
Nat Genet. 2015 Aug;47(8):872-7. doi: 10.1038/ng.3349. Epub 2015 Jun 29. PubMed PMID: 26121086.

Lindner S, Henssen A, Astrahantseff K, Schulte JH.
ALK pERKs up MYCN in neuroblastoma.
Sci Signal. 2014 Oct 28;7(349):pe27. doi: 10.1126/scisignal.2005940. PubMed PMID: 25351246.

Henssen A, Thor T, Odersky A, Heukamp L, El-Hindy N, Beckers A, Speleman F, Althoff K, Schäfers S, Schramm A, Sure U, Fleischhack G, Eggert A, Schulte JH.
BET bromodomain protein inhibition is a therapeutic option for medulloblastoma.
Oncotarget. 2013 Nov;4(11):2080-95. PubMed PMID: 24231268

Collaboration partners

Richard Koche, PhD, Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center

Wei Zhang, PhD, University of Massachusetts Boston, Center for Green Chemistry, College of Science and Mathematics 

Prof. Dr. Johannes Schulte, Charité – University Medicine Berlin, Pediatric Hematology and Oncology 

Dr. Sascha Sauer & Dr. Tomasz Zemojtel, Berlin Institute of Health (BIH) Genomics Facility

Prof. Dr. Matthias Selbach, Max-Delbrück Zentrum für Molekulare Medizin (MDC), Abteilung für Proteindynamik 

Alex Kentsis, M.D., PhD, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center 

Birgitte Regenberg, PhD, Department of Biology, University of Kopenhagen