III. Medizinische Klinik (Hämatologie und Onkologie)



Arbeitsgruppe „Immune Regulation in cancer and stem cell transplantation“

Prinicipal Investigator:

PD Dr. med. Hendrik Poeck

Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie (Direktor: Prof. Dr. Florian Bassermann)
Technische Universität München
Klinikum rechts der Isar

Phone:     +49 89 4140 4111
Fax:         +49 89 4140 4825
E-Mail:      hendrik.poeck(a)tum.de

A)    Lab members:


Postdoctoral Fellows:

PD Dr. med. Simon Heidegger (MD), Senior Scientist (TUM, Department of Hematology and Oncology, since 2013, experiments running;

  • Scholar Else Kröner-Fresenius-Stiftung Forschungskolleg München (since 2015)
  • Best of Congress at DGHO 2015 (Talk: “Synergistische Wirkung von RIGI Agonisten und Checkpoint Blockade in der Tumor Immuntherapie”)
  • Best of Congress at 32. Deutscher Krebskongress 2016 (Talk: “Activation of the cytosolic RNA receptor RIG-I in tumor and immune cells triggers efficient anti-tumor immunity and synergizes with checkpoint blockade”)
  • Winner of the 3rd Immunotherapy of Cancer conference 2016 (ITOC3) Poster Award
  • Württembergischer Cancer Award (Nachwuchspreis) 2016
  • Habilitation (PD Dr. med) 04/2017
  • DKTK Best Highlight Talk of Young Scientists 2017
  • DGHO Young Investigator Award 2017
  • ASH Abstract Achievement Award 2017
  • ASCO Merit Award 2018
  • Scholar of EHA ASH TRTH Programm 2019

Erik Thiele-Orberg, (MD, Ph.D), Postdoctoral Fellow (TUM, Department of Hematology and Oncology, since 2017)

  • Scholar Else Kröner-Fresenius-Stiftung Forschungskolleg (Start 11/ 2017)
  • Darmkrebs-Präventionspreis 2017.

Graduate (PhD) students:

Sascha Göttert, PhD Student (TUM Graduate School (TUM-GS) and Department of Hematology and Oncology, since 2018, experiments running)

Medical Students (cand.med):

Gabriel Eisenkolb, cand. med. (TUM Graduate School (TUM-GS), “Promotionsprogramm translational medicine”, since 2014, experiments running)


Florian Stritzke, cand. med. (TUM Graduate School (TUM-GS), “Promotionsprogramm translational medicine”, since 2016, experiments running)

Research Assistant:  

Tatiana Nedelko (Ph.D, since 2018)

Lena Klostermeier (Biology student, since 2018)

Visiting Scientist

Esra Büyüközkan (MD, since 2018)

B)    Former members:

Postdocs:   

Julius Fischer, (MD), Postdoctoral Fellow (TUM, Department of Hematology and Oncology, since 08/2017 physician scientist at the Department of Radiotherapy and Radiation Oncology, Klinikum der Universität München, LMU):

  • Doktoranden-Förderpreis 2018 der Deutschen Gesellschaft für Hämatologie und Onkologie (DGHO)

Michael Bscheider (MD), Postdoctoral Fellow (Technical University of Munich, Department of Hematology and Oncology; from 01/2012-06/2013); 2013-2017 Postdoctoral Fellow at Stanford University, Eugene Butchers laboratory; now Senior Scientist at Roche))

Chia-Ching Lin, PhD.; Postdoctoral Fellow (TUM, Department of Hematology and Oncology, 10/2013-05/2015; now Product Support Manager at Thermo Fisher)


PD Dr. med. Silvia Spoerl (MD), Senior Scientist (TUM, Department of Hematology and Oncology, 2013-2017)

  • Habilitation 2018

Students (Ph.D and cand. med.):

2013-2018    Alexander Wintges, PhD (TUM Graduate School (TUM-GS) and Department of Hematology and Oncology (experiments finished; grade: cum laude), now Junior Product manager at Sobi

2013-2017    Sarah Bek, PhD (TUM Graduate School (TUM-GS) and Department of Hematology and Oncology (experiments finished; proposed grade: summa cum laude)

2012-2016    Julius Fischer, cand. med. (MD) (TUM Graduate School (TUM-GS), “Promotionsprogramm translational medicine”, since 2012, experiments finished, proposed grade: summa cum laude)

2013-2016     Vera Otten, cand. med. (MD) (TUM Graduate School (TUM-GS), “Promotionsprogramm translational medicine”, since 2013, experiments finished)

2012-2013     Diana Kreppl, cand. med. (MD) (TUM Graduate School (TUM-GS), “Promotionsprogramm translational medicine”, since 2012, experiments finished)

  • Scholar of the Cornell-Program between TUM – Weil Cornell, New York, USA
  • Now Internal Medicine Resident at Macneal Hospital, Loyola Medicine, Berwyn

2006-2010  Michael Bscheider, cand. med. (MD) (summa cum laude)

2006-2008  Cornelius Maihöfer, cand. med. (MD) (summa cum laude); now Attending physician at the Department of Radiotherapy and Radiation Oncology, Klinikum der Universität München, LMU)

Research Assistant

2010-2017     Martina Schmickl (Dipl. Ing. Biol)

Current Research focus:

Research focus:

Based on our newly identified functions of cytosolic innate immune sensors in maintaining tissue homoestasis after allo-HSCT and tumor immunosurveillance, the scientific focus of our laboratory is currently centered around two topics:


1. Regenerative responses after allogeneic hematopoietic stem cell transplantation (allo-HSCT):

Our data suggest that endogenous cytosolic nucleic acid receptors including RIG-I-MAVS and cGAS-STING are involved in protecting epithelial integrity during GVHD and that therapeutic activation of RIG-I/MAVS can be exploited therapeutically to maintain epithelial barrier integrity and prevent GVHD. Our goal is to characterize the role of intestinal microbiota (bacterial / fungal) on the ISC compartment and immune system after damage induced by allo-HSCT and at understanding the innate immune pathways that can regulate barrier function after inflammatory tissue damage. We hypothesize that (i) endogenous bacteria and fungi will modulate the production of factors that are critical for intestinal homeostasis and self-renewal, and possibly support tissue regeneration by directly or indirectly activating of Lgr5+ ISC and/or its niche (Paneth cells) from intestinal pathology during pre-transplant conditioning or GVHD and (ii) microbiota (bacterial and/or fungal)-mediated tissue regeneration during GVHD is regulated by the indicated innate immune pathways. Clinical strategies to administer respective ligands to cancer patients before stem cell transplantation to prevent GVHD will be developed.


2. Mechanisms of immune evasion caused by aberrant innate nucleic acid receptor signaling in tumor cells and their tumor microenvironment:

Our preliminary data identify tumor-intrinsic RIG-I signaling as a fundamental requirement for natural and therapy-mediated (immune checkpoint blockade (ICB)) antitumor immunity. Yet, malignant melanomas can evade IFN-I-dependent immune surveillance, implicating immuno-inhibitory mechanisms that may contribute to immune escape of melanoma and render these innate pathways insensitive to activation. Our goal is to define the contributions of aberrant (defective) tumor-intrinsic and host-dependent RIG-I/MAVS and cGAS/STING signaling during development and immunosurveillance of melanoma and other cancers as well as to identify the mechanisms that drive disease resistance and response to established immunotherapy protocols (i.e. ICB, radiation therapy, demethylating agents). We hypothesize that aberrant cytosolic NA sensing and subsequent failure to activate IFN pathways in both tumor and host cells will be central for melanoma development and systemic disease manifestation, possibly via induction of tumor-intrinsic resistance programs and immune suppressive mechanisms in the tumor microenvironment that renders these pathways inactive to stimulation. We anticipate that our results will yield significant insights into improving outcomes of cancer patients as well as reveal molecular processes that are fundamental to immune –cancer cell communication. Finally, we aim to initiate clinical trials in patients with advanced cancer to test the hypothesis that combining RIG-I agonists with ICB may allow to reduce inter-individual variabilities in clinical responses.


Applications:


Written applications including CV and the names of 2 professional referees are welcome and should be forwarded by email to PD Dr. Hendrik Poeck (Hendrik.poeck(a)tum.de). We are part of the Alexander von Humboldt-Foundation Network and of the EMBO Young Investigator Programme (http://embo.org/funding-awards/young-investigators).


Funding

EMBO (Young Investigator Programme)

European Hematology Association (EHA)

DKMS Foundation for Giving Life (DKMS)

SFB 1335 (German research foundation (DFG))

SFB 1371 (German research foundation (DFG))

Else-Kröner Fresenius-Stiftung (EKFS)

Promotionsprogramm „Translationale Medizin“ of the TU München


Selected publications


1.    Fischer JC*, Bscheider M*, Eisenkolb G*, Lin CC, Wintges A, Otten V, Lindemans CA, Heidegger S, Rudelius M, Monette S, Porosnicu Rodriguez KA, Calafiore M, Liebermann S, Liu C, Lienenklaus S, Weiss S, Kalinke U, Ruland J, Peschel C, Shono Y, Docampo M, Velardi E, Jenq RR, Hanash AM, Dudakov JA, Haas T, van den Brink MRM*#, Poeck H.*# RIG-I/MAVS and STING signaling promote epithelial integrity during irradiation and immune-medited tissue injury. Sci Transl Med 2017;9. *#contributed equally

2.    Fischer JC, Wintges A, Haas T, Poeck H. Assessment of mucosal integrity by quantifying neutrophil granulocyte influx in murine models of acute intestinal injury. Cell Immunol 2017; 316:70-76.

3.    Fischer JC, Otten V, Drees C, Schmickl M, Heidegger S, Beyaert G, van Loo G, Li XC, Peschel C, Schmidt-Supprian M, Haas T, Spoerl S, Poeck H. NF-κB regulator A20 modulates thymic regulatory T cell development. J Immunol. 2017;199:2356-2365.

4.    Heidegger S, van den Brink MR, Haas T, Poeck H. The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation. Front Immunol 2014;5:337.

5.    Jankovic D, Ganesan J, Bscheider M, Stickel N, Weber FC, Guarda G, Follo M, Pfeifer D, Tardivel A, Ludigs K, Bouazzaoui A, Kerl K, Fischer JC, Haas T, Schmitt-Gräff A, Manoharan A, Müller L, Finke J, Martin S.F, Gorka O, Peschel C, Ruland J, Idzko M, Duyster J, Holler E, French LE, Poeck H*#, Contassot E*#, Zeiser R*#. The Nlrp3 inflammasome regulates acute graft-versus-host disease. J Exp Med 2013;210:1899-910. *#contributed equally

6.    Dann A*, Poeck H*, Croxford AL, Gaupp S, Kierdorf K, Knust M, Pfeifer D, Maihoefer C, Endres S, Kalinke U, Meuth SG, Wiendl H, Knobeloch KP, Akira S, Waisman A, Hartmann G, Prinz M. Cytosolic RIG-I-like helicases act as negative regulators of sterile inflammation in the CNS. Nat Neurosci 2011;15, 98-106. * contributed equally

7.    Poeck H*, Bscheider M*, Gross O*, Finger K, Roth S, Rebsamen M, Hannesschläger N, Schlee M, Rothenfusser S, Barchet W, Kato H, Akira S, Inoue S, Endres S, Peschel C, Hartmann G*, Hornung V*, Ruland J*. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat Immunol. 2010;11:63-9. *contributed equally

8.    Gross O*, Poeck H*, Bscheider M, Dostert C, Hannesschläger N, Endres S, Hartmann G, Tardivel A, Schweighoffer E, Tybulewicz V, Mocsai A, Tschopp J, Ruland J. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature. 2009;459:433-6. *contributed equally

9.    Besch R*, Poeck H*, Hohenauer T, Senft D, Häcker G, Berking C, Hornung V, Endres S, Ruzicka T, Rothenfusser S, Hartmann G. Proapoptotic signalling by RIG-I and MDA-5 results in type I interferon independent apoptosis in melanoma. J Clin Invest 2009; 119, 2399-411. *contributed equally

10.    Poeck H*, Besch R*, Maihoefer C, Renn M, Tormo D, Morskaya S, Kirschnek S, Gaffal E, Landsberg J, Hellmuth J, Schmidt A, Anz D, Bscheider M, Schwerd T, Berking C, Bourquin C, Kalinke U, Kremmer E, Kato H, Akira S, Meyers R, Häcker G, Neuenhahn M, Busch D, Ruland J, Rothenfusser S, Prinz M, Hornung V, Endres S, Tüting T, Hartmann G. 5’-triphosphate siRNA: turning gene-silencing and RIG-I activation against melanoma. Nat Med 2008; 4, 1256-63; *contributed equally








2010 · III. Medizinische Klinik (Hämatologie / Onkologie) am Klinikum rechts der Isar der Technischen Universität München