Arbeitsgruppe Prof. Dr. med. Oliver T. Keppler

Das Keppler-Labor erforscht die grundlegenden Prinzipien der Virus-Wirt-Interaktionen, insbesondere bei den pandemischen Erregern HIV und SARS-CoV-2, sowie die spezifischen Mechanismen der Resistenz gegen Chemotherapie bei verschiedenen bösartigen Erkrankungen. Mithilfe modernster Technologie und primärer Modellsysteme versuchen wir, die durch HIV ausgelöste Zerstörung des Immunsystems und die Fähigkeit des Virus, ruhende CD4-T-Zellen zu infizieren und eine Latenz zu etablieren, zu entschlüsseln. Im Kampf gegen SARS-CoV-2 testen wir neue antivirale Ansätze und versuchen, mit Hilfe von genetischen und Hochdurchsatz-Screening-Ansätzen medikamentöse zelluläre Wege zu identifizieren. An der Schnittstelle zwischen Virologie und Onkologie untersuchen wir die SAMHD1-abhängige Resistenz gegen Chemotherapie auf der Basis von Nukleosidanaloga und entwickeln SAMHD1-gerichtete Strategien, um die therapeutischen Möglichkeiten für schwer zu behandelnde hämatologische und solide Tumore zu erweitern.

Zur Arbeitsgruppe


Prof. Dr. med. Oliver T. Keppler

Oliver T. Keppler, MD, is Professor of Virology and Chairman of Virology at the Max von Pettenkofer Institute at LMU München. Oliver Keppler grew up in Freiburg i. Br. in Germany and completed the International Baccalaureate at the United World College of the Atlantic in Wales. He attended Medical School in Heidelberg and Freiburg and was trained in Internal Medicine at the Kantonsspital Bruderholz, Baselland, Switzerland. He completed his MD thesis at the German Cancer Research Center (DKFZ) in Heidelberg. Following postdoctoral periods at the DKFZ and at the Gladstone Institute of Virology and Immunology, University of California, in San Francisco, USA, he became junior group leader at the Department of Virology of Ruprecht-Karls-Universität in Heidelberg. Following completion of his habilitation and his medical training in microbiology, virology and epidemiology, he was appointed in 2012 Director of the Institute of Medical Virology of the University Hospital of Goethe-Universität in Frankfurt a. M. In 2015 he assumed his current position at the Max von Pettenkofer Institute in Munich.

© Jan Greune


Aktuelle Gruppenmitglieder

Oliver T. Keppler, MD, professor, principal investigator, chair of virology

Tom Baldow, MSc, PhD student
Phone: 49 89 2180 78123

Marie L. Bischof, MSc, PhD student
Phone: +49 89 2180 78125

Daniela Durkowitzer, technician
Phone: +49 89 2180 78125

Svenja Feldmann, MD
Phone: +49 89 2180 72833

Ritika Khatri, MSc, PhD student
Phone: +49 89 2180 78118

Yeonsu Kim, PhD, postdoctoral fellow
Phone: + 49 89 2180 78010

Olivier Klop, MD student
Phone: +49 89 2180 78123

Ina Koeva-Slancheva, technician, lab manager
Phone: +49 89 2180 78125

Bianca Köhler, postgraduate researcher
Phone: +49 89 2180 78010

Gaia Lupoli, PhD, postdoctoral fellow
Phone: +49 89 2180 78118

Michele Mascia, MSc, technician
Phone: +49 89 2180 78123

Milena Milakovic Obradovic, PhD, postdoctoral fellow
Phone: +49 89 2180 78118

Goreti Teresia Atieno Omollo
Phone: +49 89 2180 78123

Fabiana Palmiero, MSc, PhD student
Phone: +49 89 2180 78118

Adrian Ruhle, MD student (FöFoLe programme/DZIF fellow)
Phone: +49 89 2180 78123

Pauline Sigge, MSc, PhD student
Phone: +49 89 2180 78123

Niklas Teichert, MD student (FöFoLe programme)
Phone: +49 89 2180 78123

Javier Mauricio Villamizar Cujar, MSc, technician
Phone: +49 89 2180 78123

Paul R. Song Wratil, MD, PhD, postdoctoral fellow
Phone: +49 89 2180 78010

Hsiu Hui Yang, MSc, PhD student
Phone: +49 89 2180 78118

Ehemalige Gruppenmitglieder

  • Tarek Adam (visiting medical student)
  • Manuel Albanese (postdoctoral fellow)
  • Ina Ambiel (technician)
  • Julia Bitzegeio (Diploma student)
  • Simone Boos (technician)
  • Paul Burda (Master student)
  • Elina Erikson (PhD student)
  • Michael Färber (PhD student)
  • Kerstin Ganter (technician)
  • Silvia Geuenich (PhD student)
  • Christine Goffinet (PhD student, postdoctoral fellow)
  • Ebrahim Hassan (Master student)
  • Nikolas Herold (MD, post-graduate researcher)
  • Verena Jakobi (technician)
  • Klara Kaaden (Master student)
  • Christian Kern (Bachelor student)
  • Margarethe Martin (technician)
  • Nico Michel (postdoctoral fellow)
  • Lena Oberbremer (technician)
  • Katharina Pauli (MD student)
  • Claudia Rückert (Master student)
  • Daniel Rupp (MD student)
  • Kristina Schenkova (postdoctoral fellow)
  • Sarah Schmidt (PhD student, postdoctoral fellow)
  • Lismarie Schüller (technician)
  • Sarah-Marie Schwarz (PhD student)
  • Lena Stegmann (technician)
  • Stephanie Venzke (PhD student)
  • Ariane Zutz (postdoctoral fellow)
  • Christian Schölz (senior postdoctoral fellow)
  • Helena Lejk (technician)
  • Hanna-Mari Baldauf (Master student, PhD student, postdoctoral fellow, staff scientist)
  • Verena Siegert (MD student)
  • Lisa Gregor (Bachelor student)
  • Johanna Döring, (technician)
  • Jelica Gencel Augusto (Bachelor of Science)
  • Burak Karakoc (Project Management)
  • Jennifer Mittermaier (Bachelor of Science)
  • Katharina Kotter (Bachelor of Science)
  • Katharina Hofmann (technician)
  • Tamara Pflantz, M.Sc. (Project management)
  • Marcel Stern (PhD student, postdoctoral fellow)
  • Stephanie Schneider (PhD student)
  • Qianhao Xiao (PhD student)
  • Irina Badell García (MSc)
  • Ernesto Mejías-Pérez (PhD, postdoctoral fellow, LMU Research Fellow)
  • Kullyanee Panyawicha (MSc, technician)
  • Hong-Ru Chen (PhD, postdoctoral fellow, Fellow of the Ministry of Science and Technology of Taiwan)
  • Ana Moyano de las Muelas (PhD, postdoctoral fellow)
  • Nils Chapin (MSc, technican)
  • Laura Amann (technician)
  • Christos Dogrammatzis (PhD, postdoctoral fellow)
  • Madeleine Gapp (neé Roll) (PhD student)
  • Thimo Fuchs (technician)
© Max von Pettenkofer-Institut


HIV reservoir and immunodestruction

HIV/AIDS has become one of the most devastating pandemics in recorded history. AIDS is the fourth-biggest global killer and the leading cause of death in Africa. HIV/AIDS persists as a major cause of morbidity also in Western societies, since currently available pharmacotherapies can only partly control, but not cure this immunodestructive viral infection. Our laboratory seeks to better understand the pathological interplay of HIV with the host’s immune system and its target cells with the goal of providing new approaches for prophylaxis and therapy.

Resting CD4 T cells are at the center of several hallmarks of HIV pathogenesis: (i) Their depletion in the course of untreated HIV infection leads to the ultimate development of severe immunodeficiency, (ii) they are not permissive for productive HIV infection due to highly effective intrinsic immune responses, (iii) yet constitute a key cell type of the latent HIV reservoir, from which the virus rebounds upon discontinuation of antiretroviral therapy. We are seeking molecular understanding of this complex and in part seemingly contradicting virus-host interaction.

To this end, we have developed innovative methodology for the rapid, efficient and activation-neutral gene editing of polyclonal resting CD4 T cells allowing unprecedented functional analyses (Albanese, Ruhle et al., Nature Methods 2021).

We are addressing the following questions in resting CD4 T cells:

  • Establish the relevance of cellular restriction factors as part of the intrinsic immune response in regulating HIV infection and the development of viral latency
  • Decipher how accessory viral proteins influence the course of HIV infection
  • Identify cellular pathways involved in HIV-induced cell death ex vivo and in vivo

In collaboration with Prof. Roberto Speck’s laboratory in Zürich, Switzerland, we are establishing a cutting-edge humanized mouse model employing gene edited hematopoietic precursors as a platform to study the biology of HIV infection in vivo.

SARS-CoV-2: Cellular regulators, antiviral drugs and neutralization

In the fight against COVID-19 we are testing novel antiviral approaches, including peptide-linked siRNAs, to reduce viral replication and disease burden in ex vivo models and in vivo.
Based on newly developed cell models, we are aiming to identify cellular pathways involved in SARS-CoV-2 replication and virus-induced cell death. To this end, we are employing an unbiased genetic survival screen to identify important cellular factors. In addition, we are performing a high-throughput screen using a complex small molecule library to identify lead compounds for drug development.
In addition, we are elucidating the neutralizing activity of sera from COVID-19 patients and vaccinated individuals to SARS-CoV-2 variants of concern using a newly developed high-throughput assay based on authentic virus.

SAMHD1-dependent chemoresistance and approaches to overcome it

Nucleoside analogs frequently constitute the backbone of chemotherapy regimens in malignant diseases, however success is variable and often unpredictable. The identification of biomarkers to guide treatment decisions as well as novel therapeutic interventions to overcome chemoresistance are urgently needed. Together with the group of Prof. Jindrich Cinatl in Frankfurt we discovered that expression of SAMHD1 hydrolyzes and thus inactivates important metabolites of several of these nucleoside analogs, including cytarabine, and, importantly, predictes therapeutic success in patients with acute myeloid leukemia (AML) (Schneider et al., Nature Medicine 2017; Oellerich et al., Nature Communications 2019).

More recent studies elucidated the impact of SAMHD1 on other chemotherapeutics (Rothenburger et al., Communications Biology 2020) and differences in intrinsic and acquired drug resistance (Rothenburger et al., Journal of Experimental & Clinical Cancer Research 2021).

Our major goals are to (i) explore the breadth of this specific mode of chemoresistance in other hematological and solid tumors, (ii) to advance different strategies to target SAMHD1 and (iii) gain molecular understanding for SAMHD1’s biological functions in physiology and cancer.


Top 10 Publikationen

Albanese A, Chen HR, Gapp M, Muenchhoff M, Yang HH, Peterhoff D, Hoffmann K, Xiao Q., Ruhle A, Ambiel I, Schneider S, Mejías Pérez, E, Stern M Wratil PR, Hofmann K, Amann L, Jocham L, Fuchs T, Ulivi AF, Besson-Girard S, Weidlich S, Schneider J, Spinner CD, Sutter K, Dittmer D, Humpe A, Baumeister P, Wieser A, Rothenfusser S, Bogner J, Roider J, Knolle P, Hengel H, Wagner R, Laketa V, Facker OT, Keppler OT. Receptor Transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells. Cell Rep Med 2024 Apr 16; 5(4):101483. doi: 10.1016/j.xcrm.2024.101483. Epub 2024 Apr 4.
Keppler-Hafkemeyer A*, Greil C, Wratil PR, Shoumariyeh K, Stern M, Hafkemeyer A, Ashok D, Hollaus A, Lupoli G, Priller A, Bischof ML, Ihorst G, Engelhardt M, Marks R, Finke J, Bertrand H, Dächert C, Muenchhoff M, Badell I, Emmerich F, Halder H, Spaeth PM, Knolle PA, Protzer U, von Bergwelt-Baildon M, Duyster J, Hartmann TN, Moosmann A, Keppler OT*. Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma. Nature Cancer (1):81-95 (2023).
Wratil PR, Stern M, Priller A, Willmann A, Almanzar G, Vogel E, Feuerherd M, Cheng CC, Yazici S, Christa C, Jeske S, Lupoli G, Vogt T, Albanese M, Mejías-Pérez E, Bauernfried S, Graf N, Mijocevic H, Vu M, Tinnefeld K, Wettengel J, Hoffmann D, Muenchhoff M, Daechert C, Mairhofer H, Krebs S, Fingerle V, Graf A, Steininger P, Blum H, Hornung V, Liebl B, Überla K, Prelog M, Knolle P, Keppler OT*, Protzer U*. Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern. Nature Medicine 28(3):496-503 (2022).
Albanese M*, Ruhle A, Mittermaier J, Mejías-Pérez E, Madeleine Gapp, Linder A, Schmacke NA, Hofmann K, Hennrich AA, Levy DN, Humpe A, Conzelmann K-K, Hornung V, Fackler OT, Keppler OT*. Rapid, efficient and activation-neutral gene editing of polyclonal primary human resting CD4+ T cells allows unprecedented functional analyses. Nature Methods 19(1):81-89 (2022).
Oellerich T, Schneider C, Thomas D, Knecht KM, Buzovetsky O, Kaderali L, Schliemann C, Bohnenberger H, Angenendt L, Hartmann W, Wardelmann E, Rothenburger T, Mohr S, Scheich S, Comoglio F, Wilke A, Ströbel P, Serve H, Michaelis M, Ferreirós N, Geisslinger G, Xiong Y, Keppler OT*, Cinatl J Jr*. Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML. Nature Communications 2;10(1):3475 (2019).
Baldauf HM, Stegmann L, Schwarz SM, Ambiel I, Trotard M, Martin M, Burggraf M, Lenzi GM, Lejk H, Pan X, Fregoso OI, Lim ES, Abraham L, Nguyen LA, Rutsch F, König R, Kim B, Emerman M, Fackler OT, Keppler OT. Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells. Proceedings of the National Academy of Sciences USA 114(10):2729-2734 (2017).
Schneider C, Oellerich T, Baldauf HM, Schwarz SM, Thomas D, Flick R, Bohnenberger H, Kaderali L, Stegmann L, Cremer A, Martin M, Lohmeyer J, Michaelis M, Hornung V, Schliemann C, Berdel WE, Hartmann W, Wardelmann E, Comoglio F, Hansmann ML, Yakunin AF, Geisslinger G, Ströbel P, Ferreirós N, Serve H, Keppler OT*, Cinatl J Jr.*. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia. Nature Medicine 23(2):250-255 (2017).
Baldauf HM+, Pan X.+, Erikson E, Schmidt S, Daddacha W, Burggraf M, Schenkova K, Ambiel I, Wabnitz G, Gramberg T, Panitz S, Flory E, Landau NR, Sertel S, Rutsch F, Lasitschka F, Kim B, König R, Fackler OT*, Keppler OT*. SAMHD1 restricts HIV-1 infection in resting CD4+ T cells. Nature Medicine 18:1682-1687 (2012).
Erikson E, Adam T, Schmidt S, Lehmann-Koch J, Over B, Goffinet C, Harter C, Bekeredjian-Ding I, Sertel S, Lasitschka F, Keppler OT. In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans. Proceedings of the National Academy of Sciences USA 108(33):13688-93 (2011).
Goffinet C, Allespach I, Homann S, Tervo HM, Habermann A, Rupp D, Oberbremer L, Kern C, Tibroni N, Welsch S, Krijnse-Locker J, Banting G, Kräusslich HG, Fackler OT, Keppler OT. HIV-1 antagonism of CD317 is species-specific and involves Vpu-mediated proteasomal degradation of the restriction factor. Cell Host & Microbe 5:285-297 (2009).
Goffinet C, Allespach I, Keppler OT. HIV-susceptible transgenic rats allow rapid preclinical evaluation of antiviral compounds targeting virus entry or reverse transcription. Proceedings of the National Academy of Sciences USA 104:1015-1020 (2007).



  • Rolf-Becker-Preis (Medizinische Fakultät der LMU München, Stiftung „Rufzeichen Gesundheit!“) 2022: Paul R. Wratil, Marcel Stern, Alina Priller, Oliver T. Keppler
  • DZIF-Promotionspreis der Gesellschaft für Virologie (GfV) 2019: Manuel Albanese
  • Postdoktorandenpreis für Virologie 2018 der Robert-Koch-Stiftung: Maximilian Münchhoff
  • AIDS Forschungspreis 2017 der Deutschen Gesellschaft für Infektiologie (DGI): Maximilian Münchhoff
  • Postdoktoranden-Preis für Virologie 2013 der Robert-Koch-Stiftung: Hanna-Mari Baldauf
  • AIDS-Forschungspreis der H.W. & J. Hector-Stiftung 2013: Oliver T. Keppler
  • Heinz-Ansmann-Preis für AIDS-Forschung 2012: Oliver T. Keppler
  • Postdoktoranden-Preis für Virologie 2012 der Robert-Koch-Stiftung: Christine Goffinet
  • Wolfgang-Stille Preis 2010 der Paul-Ehrlich-Gesellschaft f. Chemotherapie: Oliver T. Keppler and Christine Goffinet
  • Nachwuchsforscherpreis 2009 der Deutschen AIDS Gesellschaft: Hanna-Mari Baldauf (née Tervo)
  • Loeffler-Frosch-Preis 2008 der Gesellschaft für Virologie: Oliver T. Keppler
  • Hygiene-Preis 2007 der Rudolf Schülke Stiftung: Christine Goffinet, Ina Ambiel (née Allespach), Oliver T. Keppler
  • Innovationspreis 2007 der BioRegionen Deutschlands: Oliver T. Keppler
  • AIDS Forschungspreis 2007 (Deutsche Gesellschaft für Infektiologie): Christine Goffinet and Oliver T. Keppler