Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie | CVK 

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AG Priv.-Doz. Dr. med. Olaf Penack

The aim of our clinical studies and preclinical research is to increase knowledge in the field of transplantation biology. My lab is working on the development of strategies for prevention and treatment of acute graft-versus-host-disease (GVHD) after hematopoietic stem cell transplantation (HSCT). One specific focus is the role of the endothelium for HSCT biology. The main topics of our clinical research are GVHD and infectious diseases in immunocompromised hosts.

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Die Forschung der AG Penack

Das Ziel des zweiten Schwerpunkts unserer Arbeit ist es, unser Verständnis der molekularen Mechanismen bei der Initiierung der GVHD zu verbessern. Aktuelle Forschungsergebnisse heben die Bedeutung von Wechselwirkungen zwischen mikrobiell assoziierten Molekülen (pathogen associated molecular patterns, PAMPs) und Rezeptoren des angeborenen Immunsystems (pathogen recognition receptors, PRRS) für die Kontrolle der adaptiven Immunantwort bei entzündlichen Erkrankungen hervor. Wir möchten aufzuklären, wie die GVHD durch das Zusammenspiel von mikrobiellen Molekülen und angeborener Immunität reguliert wird. Derzeit untersuchen wir die Bedeutung eines dieser PRRs (NOD2) in Maus-Modellen der GVHD. Unsere Daten stehen im Einvernehmen mit klinischen Berichten, die zeigen, dass Patienten mit Mutationen im Gen NOD2 eine höhere Inzidenz der GVHD haben, was auf eine wichtige Funktion von NOD2-Rezeptoren in der Pathophysiologie der GVHD hindeutet.

Prof. Dr. med. Olaf Penack

Oberarzt der Klinik, Ärztliche Leitung CAR T-Zell-Therapie

CVK: Campus Virchow-Klinikum

Projekte
Team

Aktuelles

Ausgewählte Publikationen

Preclinical

  • Endothelial damage is aggravated in acute GvHD and could predict its development. Mir E, Palomo M, Rovira M, Pereira A, Escolar G, Penack O, Holler E, Carreras E, Diaz-Ricart M.Bone Marrow Transplant. 2017 Jun 26. PubMed
  • The Role of Lymphangiogenesis and its Inhibition during Graft-versus-Host Disease. Mertlitz S, Shi Y, Kalupa M, Grötzinger C, Mengwasser J, Riesner K, Cordes S, Elezkurtaj S, Penack O. Blood. 2017 Mar 30;129(13):1865-1875
  • Initiation of acute graft-versus-host disease by angiogenesis. Riesner K, Shi Y, Jacobi A, Kraeter M, Kalupa M, McGearey A, Mertlitz S, Cordes S, Schrezenmeier J.F, Mengwasser J, Westphal S, Perez-Hernandez D, Schmitt C, Dittmar G, Guck J, Penack O. Blood. 2017 Apr 6;129(14):2021-2032
  • Cathepsin E regulates dendritic cell motility during graft-versus-host disease. Mengwasser J, Babes L, Cordes S, Mertlitz S, Riesner K, Shi Y, McGearey A, Kalupa M, Reinheckel T, Penack O. Front Immunol. 2017 Mar 1;8:203
  • The green tea catechin EGCG ameliorates GVHD. Westphal S, Wilke A, Rudloff S, Penack O. 2016. PLoS One. 2017 Jan 19;12(1):e0169630
  • Organ siderosis and hemophagocytosis during acute graft-versus-host disease. Nogai A, Shi Y, Pérez-Hernandez D, Cordes S, Mengwasser J, Mertlitz S, Riesner K, Kalupa M, Erdmann JH, Ziebig R, Dittmar G, Penack O. Haematologica. 2016 Aug;101(8):e344-6.
  • VEGF-ablation therapy reduces drug delivery and therapeutic response in ECM-dense tumors.Röhrig F, Vorlová S, Hoffmann H, Wartenberg M, Escorcia FE, Keller S, Tenspolde M, Weigand I, Gätzner S, Manova K, Penack O, Scheinberg DA, Rosenwald A, Ergün S, Granot Z, Henke E. Oncogene. 2016 Jun 6. doi: 10.1038/onc.2016.182.
  • A preclinical acute GVHD mouse model based on chemotherapy conditioning and MHC-matched transplantation. Riesner K, Kalupa M, Shi Y, Elezkurtaj S, Penack O. Bone Marrow Transplant. 2016 Mar;51(3):410-7.
  • Anti-tumor effects of anti-T-cell globulin. Westphal S, Brinkmann H, Kalupa M, Wilke A, Seitz-Merwald I, Penack O. Exp Hematol. 2014 Oct;42(10):875-82.
  • PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating GVHD. Ghosh A, Holland AM, Dogan Y, Yim NL, Rao UK, Young LF, West ML, Singer NV, Lee H, Na IK, Tsai JJ, Jenq RR, Penack O, Hanash AM, Lezcano C, Murphy GF, Liu C, Sadelain M, Sauer MG, Sant'angelo D, van den Brink MR. Cancer Res. 2013 Aug 1;73(15):4687-96.
  • Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity. Ghosh A, Dogan Y, Moroz M, Holland AM, Yim NL, Rao UK, Young LF, Tannenbaum D, Masih D, Velardi E, Tsai JJ, Jenq RR, Penack O, Hanash AM, Smith OM, Piersanti K, Lezcano C, Murphy GF, Liu C, Palomba ML, Sauer MG, Sadelain M, Ponomarev V, van den Brink MR. J Clin Invest. 2013 Jun;123(6):2654-62.
  • Inflammatory neovascularization during graft-versus-host disease is regulated by αv integrin and miR-100. Leonhardt F, Grundmann S, Behe M, Bluhm F, Dumont RA, Braun F, Fani M, Riesner K, Prinz G, Hechinger AK, Gerlach UV, Dierbach H, Penack O, Schmitt-Gräff A, Finke J, Weber WA, Zeiser R. Blood. 2013 Apr 25;121(17):3307-18.
  • Danger signals activating innate immunity in graft-versus-host disease. Zeiser R, Penack O, Holler E, Idzko M. J Mol Med (Berl). 2011 Sep;89(9):833-45.
  • The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation. Penack O, Socié G, van den Brink MR. Blood. 2011 Apr 21;117(16):4181-9.
  • Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation. Lu SX, Kappel LW, Charbonneau-Allard AM, Atallah R, Holland AM, Turbide C, Hubbard VM, Rotolo JA, Smith M, Suh D, King C, Rao UK, Yim N, Bautista JL, Jenq RR, Penack O, Na IK, Liu C, Murphy G, Alpdogan O, Blumberg RS, Macian F, Holmes KV, Beauchemin N, van den Brink MR. PLoS One. 2011;6(7):e21611.
  • Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease. Lu SX, Holland AM, Na IK, Terwey TH, Alpdogan O, Bautista JL, Smith OM, Suh D, King C, Kochman A, Hubbard VM, Rao UK, Yim N, Liu C, Laga AC, Murphy G, Jenq RR, Zakrzewski JL, Penack O, Dykstra L, Bampoe K, Perez L, Furie B, Furie B, van den Brink MR. J Immunol. 2010 Aug 1;185(3):1912-9.
  • Inhibition of neovascularization to simultaneously ameliorate graft-vs-host disease and decrease tumor growth. Penack O, Henke E, Suh D, King CG, Smith OM, Na IK, Holland AM, Ghosh A, Lu SX, Jenq RR, Liu C, Murphy GF, Lu TT, May C, Scheinberg DA, Gao DC, Mittal V, Heller G, Benezra R, van den Brink MR. J Natl Cancer Inst. 2010 Jun 16;102(12):894-908.
  • Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors. Penack O, Holler E, van den Brink MR. Blood. 2010 Mar 11;115(10):1865-72.
  • The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease. Na IK, Lu SX, Yim NL, Goldberg GL, Tsai J, Rao U, Smith OM, King CG, Suh D, Hirschhorn-Cymerman D, Palomba L, Penack O, Holland AM, Jenq RR, Ghosh A, Tran H, Merghoub T, Liu C, Sempowski GD, Ventevogel M, Beauchemin N, van den Brink MR. J Clin Invest. 2010 Jan;120(1):343-56.
  • NOD2 regulates hematopoietic cell function during graft-versus-host disease. Penack O, Smith OM, Cunningham-Bussel A, Liu X, Rao U, Yim N, Na IK, Holland AM, Ghosh A, Lu SX, Jenq RR, Liu C, Murphy GF, Brandl K, van den Brink MR. J Exp Med. 2009 Sep 28;206(10):2101-10.

Clinical

  • EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis. Luft, T., Benner, A., Jodele, S., Dandoy, C. E., Storb, R., Gooley, T., Sandmaier, B. M., Becker, N., Radujkovic, A., Dreger, P. and Penack, O. Lancet Hematology 2017. In press.
  • Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ullmann AJ, Schmidt-Hieber M, Bertz H, Heinz WJ, Kiehl M, Krüger W, Mousset S, Neuburger S, Neumann S, Penack O, Silling G, Vehreschild JJ, Einsele H, Maschmeyer G; Infectious Diseases Working Party of the German Society for Hematology and Medical Oncology (AGIHO/DGHO) and the DAG-KBT (German Working Group for Blood and Marrow Transplantation). Ann Hematol. 2016 Sep;95(9):1435-55
  • Organ siderosis and hemophagocytosis during acute graft-versus-host disease. Nogai A, Shi Y, Pérez-Hernandez D, Cordes S, Mengwasser J, Mertlitz S, Riesner K, Kalupa M, Erdmann JH, Ziebig R, Dittmar G, Penack O. Haematologica. 2016 Aug;101(8):e344-6.
  • CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)-Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Schmidt-Hieber M, Silling G, Schalk E, Heinz W, Panse J, Penack O, Christopeit M, Buchheidt D, Meyding-Lamadé U, Hähnel S, Wolf HH, Ruhnke M, Schwartz S, Maschmeyer G. Ann Oncol. 2016 Jul;27(7):1207-25
  • Anti-Aspergillus immunoglobulin-G testing in serum of hematopoietic stem cell transplant recipients. Erdmann JH, Graf B, Blau IW, Fischer F, Timm G, Hemmati P, Arnold R, Penack O. Transpl Infect Dis. 2016 Jun;18(3):354-60
  • Influence of pre-existing invasive aspergillosis on allo-HSCT outcome: a retrospective EBMT analysis by the Infectious Diseases and Acute Leukemia Working Parties. Penack O, Tridello G, Hoek J, Socié G, Blaise D, Passweg J, Chevallier P, Craddock C, Milpied N, Veelken H, Maertens J, Ljungman P, Cornelissen J, Thiebaut-Bertrand A, Lioure B, Michallet M, Iacobelli S, Nagler A, Mohty M, Cesaro S. Bone Marrow Transplant. 2016 Mar;51(3):418-23
  • Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome. Radujkovic A, Becker N, Benner A, Penack O, Platzbecker U, Stölzel F, Bornhäuser M, Hegenbart U, Ho AD, Dreger P, Luft T. Oncotarget. 2015 Oct 27;6(33):35095-106
  • Antiviral prophylaxis in patients with solid tumours and haematological malignancies--update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Sandherr M, Hentrich M, von Lilienfeld-Toal M, Massenkeil G, Neumann S, Penack O, Biehl L, Cornely OA. Ann Hematol. 2015 Sep;94(9):1441-50.
  • Association between low uric acid levels and acute graft-versus-host disease. Ostendorf BN, Blau O, Uharek L, Blau IW, Penack O. Ann Hematol. 2015 Jan;94(1):139-44
  • Single-Nucleotide Polymorphisms Within the Thrombomodulin Gene (THBD) Predict Mortality in Patients With Graft-Versus-Host Disease. Rachakonda SP, Penack O, Dietrich S, Blau O, Blau IW, Radujkovic A, Isermann B, Ho AD, Uharek L, Dreger P, Kumar R, Luft T. J Clin Oncol. 2014 Oct 20;32(30):3421-7
  • Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Tacke D, Buchheidt D, Karthaus M, Krause SW, Maschmeyer G, Neumann S, Ostermann H, Penack O, Rieger C, Ruhnke M, Sandherr M, Schweer KE, Ullmann AJ, Cornely OA. Ann Hematol. 2014 Sep;93(9):1449-56
  • Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology (DGHO). Vehreschild JJ, Böhme A, Cornely OA, Kahl C, Karthaus M, Kreuzer KA, Maschmeyer G, Mousset S, Ossendorf V, Penack O, Vehreschild MJ, Bohlius J; Infectious Diseases Working Party of the Society for Haematology and Medical Oncology. Ann Oncol. 2014 Sep;25(9):1709-18.
  • Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO). Penack O, Becker C, Buchheidt D, Christopeit M, Kiehl M, von Lilienfeld-Toal M, Hentrich M, Reinwald M, Salwender H, Schalk E, Schmidt-Hieber M, Weber T, Ostermann H. Ann Hematol. 2014 Jul;93(7):1083-95. doi
  • Central venous catheter-related infections in hematology and oncology: 2012 updated guidelines on diagnosis, management and prevention by the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology. Hentrich M, Schalk E, Schmidt-Hieber M, Chaberny I, Mousset S, Buchheidt D, Ruhnke M, Penack O, Salwender H, Wolf HH, Christopeit M, Neumann S, Maschmeyer G, Karthaus M; Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology. Ann Oncol. 2014 May;25(5):936-47.
  • Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Mousset S, Buchheidt D, Heinz W, Ruhnke M, Cornely OA, Egerer G, Krüger W, Link H, Neumann S, Ostermann H, Panse J, Penack O, Rieger C, Schmidt-Hieber M, Silling G, Südhoff T, Ullmann AJ, Wolf HH, Maschmeyer G, Böhme A. Ann Hematol. 2014 Jan;93(1):13-32

Drittmittelförderung

  • Deutsche Forschungsgemeinschaft
  • Deutsche Krebshilfe
  • Else Kröner Fresenius-Stiftung
  • José Carreras Leukämie-Stiftung
  • Wilhelm Sander-Stiftung