Virology

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.

Current Group Members

Oliver T. Keppler, MD, professor, principal investigator, chair of virology
E-Mail: keppler@mvp.lmu.de

Tom Baldow, PhD student
E-Mail: baldow@mvp.lmu.de
Phone: +49 89 2180 78123

Marie Leonora Bischof, MSc, PhD student
E-Mail: Bischof@mvp.lmu.de
Phone: +49 89 2180 78125

Svenja Feldmann, MD
E-Mail: feldmann@mvp.lmu.de
Phone: 089 2180 72833

Thimo Fuchs, technician
E-Mail: t.fuchs@mvp.lmu.de
Phone: +49 89 2180 78125

Madeleine Gapp (neé Roll), PhD student
E-Mail: gapp@mvp.lmu.de
Phone: +49 89 2180-78123

Ritika Khatri, MSc, PhD student
Phone: +49 89 2180 78118
E-Mail: Khatri@mvp.lmu.de

Yeonsu Kim, PhD, postdoctoral fellow
E-Mail: kim@mvp.lmu.de
Phone: +49 89 2180 78010

Olivier Klop, PhD student
E-Mail: klop@mvp.lmu.de
Phone: +49 89 2180 78123

Ina Koeva-Slancheva, technician, lab manager
E-Mail: koeva@mvp.lmu.de
Phone: +49 89 2180 78125

Bianca Köhler, PhD, postdoctoral fellow
E-Mail: Koehler@mvp.lmu.de
Phone: +49 89 2180 78123

Gaia Lupoli, PhD, postdoctoral fellow
E-Mail: Lupoli@mvp.lmu.de
Phone: +49 89 2180 78123

Michele Mascia, MSc, technician
E-Mail: Mascia@mvp.lmu.de
Phone: +49 89 2180-78125

Milena Milakovic Obradovic, PhD, postdoctoral fellow
E-Mail: obradovic@mvp.lmu.de
Phone: +49 89 2180 78118

Goreti Teresia Atieno Omollo
E-Mail: Goreti.Omollo@mvp.lmu.de
Phone: +49 89 2180 78118

Fabiana Palmiero, PhD student
E-Mail: Palmiero@mvp.lmu.de
Phone: +49 89 2180 78123

Adrian Ruhle, MD student (FöFoLe programme/DZIF fellow)
E-Mail: ruhle@mvp.lmu.de
Phone: +49 89 2180 78124

Pauline Sigge, MSc, PhD student
E-Mail: sigge@mvp.lmu.de
Phone: +49 89 2180 78123

Niklas Teichert, MD student (FöFoLe programme)
E-Mail: teichert@mvp.lmu.de
Phone: +49 89 2180 78124

Javier Mauricio Villamizar Cujar, MSc, technician
E-Mail: VillamizarCujar@mvp.lmu.de
Phone: +49 89 2180 78123

Paul Robin Wratil, MD, PhD student
E-Mail: wratil@mvp.lmu.de
Phone: +49 89 2180 78123

Hsiu Hui Yang, PhD student
E-Mail: yang@mvp.lmu.de
Phone: +49 89 2180 78124

Former Group Members

• 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, technician)
• Laura Amann (technician)
• Christos Dogrammatzis, (PhD, postdoctoral fellow)

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.

Awards

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