Sos Lab

Molecular Pathology

Our lab is interested in the molecular principles that underlie the evolution of resistance against targeted therapies and the translation of genomic, transcriptomic and proteomic analyses into actionable therapeutic strategies for the treatment of lung cancer patients.

Our research focus:

The development of precision cancer medicine that aims at the specific inhibition of oncogenic targets boosted the success of translational cancer research over the past years. The identification of novel driver oncogenes such as mutant EGFR in lung adenocarcinoma patients as well as novel therapeutic strategies dramatically changed the therapeutic concepts for the treatment of virtually all cancer types. Despite the unprecedented impact of targeted therapeutics on overall survival of selected patients, the efficacy of targeted therapeutic is limited through the outgrowth of resistant clones in virtually all tumors. Finally, in small cell lung cancer, an aggressive, neuroendocrine subtype frequently associated with smoking, a lack of therapeutically accessible targets precludes an effective treatment of these tumors.

Our goals:

We are using a plethora of methods and model systems to obtain an in-depth understanding of the molecular processes which lead to drug resistance, and to identify strategies for improved treatment options for genetically defined lung cancer patients.

Our approach:

To capture the cellular networks mediating sensitivity/resistance to cancer therapies we employ CRISPR-based gain- and loss-of-function experiments including genome-wide screens with genome and transcriptome sequencing as well as animal experiments. We moreover combine innovative molecular cell biology technologies with cutting-edge computational biology methods in order to make an impact on the development of novel cancer therapies.

Principal Investigator

Univ. Prof. Dr. med.  Martin Sos

Principal Investigator

msos1@uni-koeln.de

Martin Sos

Team

Marcel Dammert
Dr. Marcel Dammert

PostDoc

Katia Garbert
Dr. Katia Garbert

Scientific Coordinator

Alena Heimsoeth
Alena Heimsoeth

PhD Student

Felix Heisel
Felix Heisel

MD Student

Stefanie Lennartz
Stefanie Lennartz

Technical Assistant

Jenny Ostendorp
Jenny Ostendorp

PhD Student

Nicole Russ
Nicole Russ

Technical Assistant

Ayla Schwäbe
Ayla Schwäbe

MD Student

Martin Sos
Univ. Prof. Dr. med.  Martin Sos

Principal Investigator

Eike Steinke
Eike Steinke

MD Student

Hannah Tumbrink
Hannah Tumbrink

PhD Student

Most important publications

  1. BrägelmannJ, Lorenz C, Borchmann S, Nishii K, Wegner J, Meder L, Ostendorp J, Ast DF, Heimsoeth A, Nakasuka T, Hirabae A, Okawa S, Dammert MA, Plenker D, Klein S, Lohneis P, Gu J, Godfrey LK, Forster J, Trajkovic-Arsic M, Zillinger T, Haarmann M, Quaas A, Lennartz S, Schmiel M, D'Rozario J, Thomas ES, Li H, Schmitt CA, George J, Thomas RK, von Karstedt S, Hartmann G, Büttner R, Ullrich RT, Siveke JT, Ohashi K, Schlee M, Sos ML. MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I. Nat Commun. 2021 Sep 17;12(1):5505.
     
  2. Dammert MA, Brägelmann J, Olsen RR, Böhm S, Monhasery N, Whitney CP, Chalishazar MD, Tumbrink HL, Guthrie MR, Klein S, Ireland AS, Ryan J, Schmitt A, Marx A, Ozretić L, Castiglione R, Lorenz C, Jachimowicz RD, Wolf E, Thomas RK, Poirier JT, Büttner R, Sen T, Byers LA, Reinhardt HC, Letai A, Oliver TG, Sos ML. MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer. Nat Commun. 2019 Aug 2;10(1):3485.
     
  3. Fassunke J, Müller F, Keul M, Michels S, Dammert MA, Schmitt A, Plenker D, Lategahn J, Heydt C, Brägelmann J, Tumbrink HL, Alber Y, Klein S, Heimsoeth A, Dahmen I, Fischer RN, Scheffler M, Ihle MA, Priesner V, Scheel AH, Wagener S, Kron A, Frank K, Garbert K, Persigehl T, Püsken M, Haneder S, Schaaf B, Rodermann E, Engel-Riedel W, Felip E, Smit EF, Merkelbach-Bruse S, Reinhardt HC, Kast SM, Wolf J, Rauh D, Büttner R, Sos ML. Overcoming EGFR(G724S)-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors. Nat Commun. 2018 Nov 7;9(1):4655.
     
  4. Plenker D, Bertrand M, de Langen AJ, Riedel R, Lorenz C, Scheel AH, Müller J, Brägelmann J, Daßler-Plenker J, Kobe C, Persigehl T, Kluge A, Wurdinger T, Schellen P, Hartmann G, Zacherle T, Menon R, Thunnissen E, Büttner R, Griesinger F, Wolf J, Heukamp L, Sos ML, Heuckmann JM. Structural Alterations of MET Trigger Response to MET Kinase Inhibition in Lung Adenocarcinoma Patients. Clin Cancer Res. 2018 Mar 15;24(6):1337-1343.
     
  5. Brägelmann J, Dammert MA, Dietlein F, Heuckmann JM, Choidas A, Böhm S, Richters A, Basu D, Tischler V, Lorenz C, Habenberger P, Fang Z, Ortiz-Cuaran S, Leenders F, Eickhoff J, Koch U, Getlik M, Termathe M, Sallouh M, Greff Z, Varga Z, Balke-Want H, French CA, Peifer M, Reinhardt HC, Örfi L, Kéri G, Ansén S, Heukamp LC, Büttner R, Rauh D, Klebl BM, Thomas RK, Sos ML. Systematic kinase inhibitor profiling identifies CDK9 as a synthetic lethal target in NUT midline carcinoma. Cell Reports. 2017 Sep 19;20(12):2833-2845.
     
  6. Plenker D, Riedel M, Brägelmann J, Dammert MA, Chauhan R, Knowles PP, Lorenz C, Keul M, Bührmann M, Pagel O, Tischler V, Scheel AH, Schütte D, Song Y, Stark J, Mrugalla F, Alber Y, Richters A, Engel J, Leenders F, Heuckmann JM, Wolf J, Diebold J, Pall G, Peifer M, Aerts M, Gevaert K, Zahedi RP, Buettner R, Shokat KM, McDonald NQ, Kast SM, Gautschi O, Thomas RK, Sos ML. Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors. Sci Transl Med. 2017 Jun 14;9(394).
     
  7. Mollaoglu G, Guthrie MR, Böhm S, Brägelmann J, Can I, Ballieu PM, Marx A, George J, Heinen C, Chalishazar MD, Cheng H, Ireland AS, Denning KE, Mukhopadhyay A, Vahrenkamp JM, Berrett KC, Mosbruger TL, Wang J, Kohan JL, Salama ME, Witt BL, Peifer M, Thomas RK, Gertz J, Johnson JE, Gazdar AF, Wechsler-Reya RJ, Sos ML*, Oliver TG (*co-corresponding author). MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition. Cancer Cell. 2017 Feb 13;31(2):270-285.
     
  8. Ortiz-Cuaran S, Scheffler M, Plenker D, Dahmen L, Scheel AH, Fernandez-Cuesta L, Meder L, Lovly CM, Persigehl T, Merkelbach-Bruse S, Bos M, Michels S, Fischer R, Albus K, König K, Schildhaus HU, Fassunke J, Ihle MA, Pasternack H, Heydt C, Becker C, Altmüller J, Ji H, Müller C, Florin A, Heuckmann JM, Nuernberg P, Ansén S, Heukamp LC, Berg J, Pao W, Peifer M, Buettner R, Wolf J, Thomas RK, Sos ML. Heterogeneous Mechanisms of Primary and Acquired Resistance to Third Generation EGFR Inhibitors. Clin Cancer Res. 2016 Oct 1;22(19):4837-4847.
     
  9. Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 28;503(7477):548-51.
     
  10. Sos ML, Dietlein F, Peifer M, Schöttle J, Balke-Want H, Müller C, Koker M, Richters A, Heynck S, Malchers F, Heuckmann JM, Seidel D, Eyers PA, Ullrich RT, Antonchick AP, Vintonyak VV, Schneider PM, Ninomiya T, Waldmann H, Büttner R, Rauh D, Heukamp LC, Thomas RK. A framework for identification of actionable cancer genome dependencies in small cell lung cancer. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17034-9.