BIOQUANT

Jan-Philipp Mallm

 

 

 

Within the Heidelberg Center for Personalized Oncology (DKFZ-HIPO), the CHromatin And RNA Methods (CHARM) lab is dedicated to develop and adapt genome-wide chromatin and RNA methods for primary patient material. Workflows for different tumor entities, such as 3D cell culture, solid tumors and PBMCs, are carefully validated.
At this stage, ChIPseq, MNase-seq, as well as low-input protocols for ATAC-seq, WGBS and RNA-seq have already been successfully applied within the HIPO program. A collection of validated antibodies for histone modifications and certain chromatin interacting proteins is available. Furthermore, we develop single-cell genomics, transcriptomics and epigenomics methods to address tumor heterogeneity.Our goal is to provide a comprehensive view on the regulation of the cancer genome to foster new strategies for personalized cancer treatment. Our goal is to provide a comprehensive view on the regulation of the cancer genome to foster new strategies for personalized cancer treatment.

Link to HIPO webpage: HIPO

 

Single cell sequencing (sc-seq) technologies are evolving fast and become more and more important for many research groups at the DKFZ. To address this need, the DKFZ single cell open lab (scOpenLab, cost center W192) will start to operate in January 2018. The scOpenLab will offer assisted access to instrumentation for processing the cells and preparing the libraries for sequencing to all DKFZ groups.

For further information and contact details please visit our webpage: scOpenLab

 

 

Within the CancerEpiSys consortium we set out to dissect the epigenetic networks associated with chronic lymphocytic leukemia (CLL) to develop novel diagnostic and therapeutic approaches for the disease. We analyzed chromatin features that are governed by an interconnected network of molecular processes that determine the cellular gene expression program. Any errors that occur in the interplay of these factors can lead to aberrant gene regulation associated with cancer. To rationalize the mode of action of novel ‘epigenetic’ drugs in cancer therapy that change properties of this network, we will dissect experimentally and mathematically the interdependence of these processes, focusing on CLL.
Furthermore we specifically investigate response to treatment within clinical trails to uncover resistance mechanisms by single-cell sequencing approaches in several leukemia subtypes such as AML and MM.

 

Scientific Background

  • Since 01/2018 Head of the DKFZ Single-cell Open Lab
  • Since 03/2017 Team Leader for Single-cell Sequencing in the Division Chromatin Networks
  • Since 10/2014 Head of the Chromatin and RNA (CHARM) methods lab, Heidelberg Center for Personalized Oncology (HIPO)
  • 01/2013 - 09/2014 Postdoc in the Research Group Genome Organization & Function, research topic: Alteration of epigenetic modifications in CLL patients
  • 10/2008 - 12/2012 PhD student in the Research Group Genome Organization & Function, research topic: Chromatin features defining potency of embryonic stem cells and tumor initiating cells
  • 2008 Master in Molecular Biotechnology

  • 2005-2006 Visiting Student University of Sussex, UK

 

Publications

Zirkel A, Nikolic M, Sofiadis K, Mallm JP, Brant L, Becker C, Altmuelle, J, Franzen J, Koke, M, Gusmao EG, Costa IG, Ullrich RT, Wagner W, Nuernberg P, Rippe K & Papantonis A (2017). Topological demarcation by HMGB2 is disrupted early upon senescence entry across cell types and induces CTCF clustering. bioRxiv 127522, doi: 10.1101/127522.

Delacher M, Imbusch CD, Weichenhan D, Breiling A, Hotz-Wagenblatt A, Träger U, Hofer AC, Kägebein D, Wang Q, Frauhammer F, Mallm JP, Bauer K, Herrmann C, Lang P, Brors B, Plass C & Feuerer M (2017). Genome-wide DNA methylation landscape defines specialization of regulatory T cells in tissues. Nat Immunol.18,1160-1172.

Brocks D, Schmidt CR, Daskalakis M, Jang HS, Shah NM, Li D, Li J, Zhang B, Hou Y, Laudato S, Lipka DB, Schott J, Bierhoff H, Assenov Y, Helf M, Ressnerova A, Islam MS, Lindroth AM, Haas S, Essers M, Imbusch CD, Brors B, Oehme I, Witt O, Lübbert M, Mallm JP, Rippe K, Will R,Weichenhan D, Stoecklin G, Gerhäuser C, Oakes CC, Wang T, Plass C (2017). DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat Genet 49, 1052-1060.

Teif VB, Mallm JP, Sharma T, Welch DBM, Rippe K, Eils R, Langowski J, Olins AL, Olins DE (2017). Nucleosome repositioning during differentiation of a human myeloid leukemia cell line. Nucleus 8, 188-204.
Molitor J, Mallm JP, Rippe K, Erdel F (2017). Retrieving chromatin patterns from deep sequencing data with correlation functions. Biophys J 112, 4473-490.
Bauer T, Trump S, Ishaque N, Thürmann L, Gu L, Bauer M, Bieg M, Gu Z, Weichenhan D, Mallm JP, Röder S, Herberth G, Takada E, Mücke O, Winter M, Junge KM, Grützmann K, Rolle-Kampczyk U, Wang Q, Lawerenz C, Borte M, Polte T, Schlesner M, Schanne M, Wiemann S, Geörg C, Stunnenberg HG, Plass C, Rippe K, Mizuguchi J, Herrmann C, Eils R, Lehmann I (2016). Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children. Mol Syst Biol 12, 861.

Mattout A, Aaronson Y, Sailaja BS, Raghu Ram EV, Harikumar A, Mallm JP, Sim KH, Nissim-Rafinia M, Supper E, Singh PB, Sze SK, Gasser SM, Rippe K, Meshorer E (2016). Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells. Genome Biol 16, 213.

Junge KM, Bauer T, Geissler S, Hirche F, Thürmann L, Bauer M, Trump S, Bieg M, Weichenhan D, Gu L, Mallm JP, Ishaque N, Mücke O, Röder S, Herberth G, Diez U, Borte M, Rippe K, Plass C, Hermann C, Stangl GI, Eils R, Lehmann I (2015). Increased vitamin D levels at birth and in early infancy increase offspring allergy risk-evidence for involvement of epigenetic mechanisms. J Allergy Clin Immunol 137, 610-613.

Mallm JP & Rippe K. (2015). Aurora kinase B regulates telomerase activity via a centromeric RNA in stem cells. Cell Rep 11, 1667-1678
Campos B, Weisang S, Osswald F, Ali R, Sedlmeier G, Bageritz J, Mallm JP, Hartmann C, von Deimling A, Popanda O, Goidts V, Plass C, Unterberg A, Schmezer P, Burhenne J, Herold-Mende C (2015). Retinoid resistance and multifaceted impairment of retinoic acid synthesis in glioblastoma. Glia 63,1850-9. 

Yearim A, Gelfman S, Shayevitch R, Melcer S, Glaich O, Mallm JP, Nissim-Rafinia M, Cohen AH, Rippe K, Meshorer E, Ast G. (2015). HP1 is involved in regulating the global impact of DNA methylation on alternative splicing. Cell Rep 10, 1122-34.

Hick M, Herrmann U, Weyer SW, Mallm JP, Tschäpe JA, Borgers M, Mercken M, Roth FC, Draguhn A, Slomianka L, Wolfer DP, Korte M, Müller UC (2015). Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity.
Acta Neuropathol 129, 21-37. 

Müller-Ott K, Erdel F, Matveeva A, Mallm JP, Rademacher A, Hahn M, Bauer C, Zhang Q, Kaltofen S, Schotta G, Höfer T, Rippe K. (2014). Specificity, propagation, and memory of pericentric heterochromatin. Mol Syst Biol 10, 746.

Teif VB, Beshnova DA, Vainshtein Y, Marth C, Mallm JP, Höfer T, Rippe K (2014). Nucleosome repositioning links DNA (de)methylation and differential CTCF binding during stem cell development. Genome Res 24, 1285-95.

Jäger N, Schlesner M, Jones DT, Raffel S, Mallm JP, Junge KM, Weichenhan D, Bauer T, Ishaque N, Kool M, Northcott PA, Korshunov A, Drews RM, Koster J, Versteeg R, Richter J, Hummel M, Mack SC, Taylor MD, Witt H, Swartman B, Schulte-Bockholt D, Sultan M, Yaspo ML, Lehrach H, Hutter B, Brors B, Wolf S, Plass C, Siebert R, Trumpp A, Rippe K, Lehmann I, Lichter P, Pfister SM, Eils R (2013). Hypermutation of the inactive X chromosome is a frequent event in cancer. Cell 155, 567-81.

Hahn M, Dambacher S, Dulev S, Kuznetsova AY, Eck S, Wörz S, Sadic D, Schulte M, Mallm JP, Maiser A, Debs P, von Melchner H, Leonhardt H, Schermelleh L, Rohr K, Rippe K, Storchova Z, Schotta G (2013). Suv4-20h2 mediates chromatin compaction and is important for cohesin recruitment to heterochromatin. Genes Dev 27, 859-72.

Teif VB, Erdel F, Beshnova DA, Vainshtein Y, Mallm JP, Rippe K (2013). Taking into account nucleosomes for predicting gene expression. Methods 62, 26-38.

Teif VB, Vainshtein Y, Caudron-Herger M, Mallm JP, Marth C, Höfer T, Rippe K (2012). Genome-wide nucleosome positioning during embryonic stem cell development. Nat Struct Mol Biol 19, 1185-92.

Caurdon-Herger M, Müller-Ott K, Mallm JP, Marth C, Schmidt U, Fejes-Tóth K, Rippe K (2011). Coding RNAs with a non-coding function: maintenance of open chromatin structure. Nucleus 2, 410-424.

Mallm JP, Tschäpe JA, Hick M, Filippov MA, Müller UC (2010). Generation of conditional null alleles for APP and APLP2. Genesis 48, 200-6.

Plaimas K, Mallm JP, Oswald M, Svara F, Sourjik V, Eils R, König R (2008). Machine learning based analyses on metabolic networks supports high-throughput knockout screens. BMC Syst Biol 24, 67.

Fatumo S, Plaimas K, Mallm JP, Schramm G, Adebiyi E, Oswald M, Eils R, König R (2009). Estimating novel potential drug targets of Plasmodium falciparum by analysing the metabolic network of knock-out strains in silico. Infect Genet Evol 9, 351-8.

 

Contact

Jan-Philipp Mallm

DKFZ & BioQuant Center

Im Neuenheimer Feld 267

69120 Heidelberg

Germany


BioQuant room 423a, 4th floor

Tel.: +49-6221-54-51322

Fax: +49 6221 54 51487


e-mail: jan-philipp.mallm (at) bioquant.uni-heidelberg.de

e-mail: j.mallm(a)dkfz.de