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Klinik für Innere Medizin IIGastroenterologie, Hepatologie, Endokrinologie und Infektiologie

Group of Christoph Neumann-Haefelin

Research interest

The focus of our research group are protective immune responses as well as immunopathology in the context of viral hepatitis (hepatitis B, C, D and E), hepatocellular carcinoma (HCC), and SARS-CoV-2 infection (COVID-19). A specific interest are mechanisms that lead to the failure of protective immune responses, including CD8+ T-cell failure and viral escape mutations. Long-term translational goals of our research are the development of novel antiviral strategies contributing to functional cure of hepatitis B and D virus infection, successful vaccination strategies against hepatitis C virus, and novel treatment options for immunocompromised patients suffering from chronic hepatitis E virus infection. In HCC, improved immunotherapies with reduced risk of adverse effects such as checkpoint inhibitor associated autoimmune disorders are an important goal. Finally, we want to contribute to an enhanced understanding of protective immunity following SARS-CoV-2 infection and vaccination, allowing an informed strategy against this ongoing pandemics.

Members

Prof. Dr. Christoph Neumann-Haefelin ( Group leader)  0761/270-32800
   
Janine Kemming (PhD student) 0761/270-35110
Dr. Julia Lang-Meli (MD) 0761/270-35110
Dr. Hendrik Luxenburger (MD) 0761/270-35110
Valerie Oberhardt (PhD student) 0761/270-35110
Elahe Salimi (PhD student) 0761/270-35110
Dr. Isabel Schulien (PhD student) 0761/270-35110
Elisa Wüstrich (BTA) 0761/270-35090
 
In addition, we work in close cooperation with the other groups of the Translational EXperimental IMmunology lab (TEXIMMED2-FR)

Funding

Our studies are supported by:

  • Sonderforschungsbereich-TRR179 (Deutsche Forschungsgemeinschaft, DFG)
  • Sonderforschungsbereich 1160: IMPATH (Deutsche Forschungsgemeinschaft, DFG)
  • NAKSYS (Else Kröner-Fresenius-Stiftung)
  • DZIF TTU Hepatitis (BMBF)
  • Sonderfördermaßnahme COVID-19 (MWK Baden-Württemberg)

Selected publications (since 2019):

  1. Schulien I*, Kemming J*, Oberhardt V*, Wild K*, Seidel LM*, Killmer S, Sagar, Daul F, Salvat Lago M, Decker A, Luxenburger H, Binder B, Bettinger D, Sogukpinar O, Rieg S, Panning M, Huzly D, Schwemmle M, Kochs G, Waller CF, Nieters A, Duerschmied D, Emmerich F, Mei HE, Schulz AR, Llewellyn-Lacey S, Price DA, Boettler T*, Bengsch B*, Thimme R*, Hofmann M*, Neumann-Haefelin C*. Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells. Nat Med 2021;27(1):78-85
  2. Schwabenland M, Salié H, Tanevski J, Killmer S, Lago MS, Schlaak AE, Mayer L, Matschke J, Püschel K, Fitzek A, Ondruschka B, Mei HE, Boettler T, Neumann-Haefelin C, Hofmann M, Breithaupt A, Genc N, Stadelmann C, Saez-Rodriguez J, Bronsert P, Knobeloch KP, Blank T, Thimme R, Glatzel M, Prinz M, Bengsch B. Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions. Immunity 2021 (in press, online available)
  3. Urban S*, Neumann-Haefelin C*, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease. Gut 2021 (in press, online available)
  4. Bettinger D, Sturm L, Pfaff L, Hahn F, Kloeckner R, Volkwein L, Praktiknjo M, Lv Y, Han G, Huber JP, Boettler T, Reincke M, Klinger C, Caca K, Heinzow H, Seifert LL, Weiss KH, Rupp C, Piecha F, Kluwe J, Zipprich A, Luxenburger H, Neumann-Haefelin C, Schmidt A, Jansen C, Meyer C, Uschner FE, Brol MJ, Trebicka J, Rössle M, Thimme R, Schultheiss M. Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival. J Hepatol 2021;74(6):1362-1372
  5. Hensel N, Gu Z, Sagar, Wieland D, Jechow K, Kemming J, Llewellyn-Lacey S, Gostick E, Sogukpinar O, Emmerich F, Price DA, Bengsch B, Boettler T, Neumann-Haefelin C, Eils R, Conrad C, Bartenschlager R, Grün D, Ishaque N, Thimme R, Hofmann M. Memory-like HCV-specific CD8<sup>+</sup> T cells retain a molecular scar after cure of chronic HCV infection. Nat Immunol 2021;22(2):229-239.
  6. Basho K, Zoldan K, Schultheiss M, Bettinger D, Globig AM, Bengsch B, Neumann-Haefelin C, Klocperk A, Warnatz K, Hofmann M, Thimme R, Boettler T. IL-2 contributes to cirrhosis-associated immune dysfunction by impairing follicular T helper cells in advanced cirrhosis. J Hepatol 2021;74(3):649-660
  7. Heim K, Binder B, Sagar, Wieland D, Hensel N, Llewellyn-Lacey S, Gostick E, Price DA, Emmerich F, Vingerhoet H, Kraft ARM, Cornberg M, Boettler T, Neumann-Haefelin C, Zehn D, Bengsch B, Hofmann M, Thimme R. TOX defines the degree of CD8+ T cell dysfunction in distinct phases of chronic HBV infection. Gut 2020 (in press, online available)
  8. Smits M, Zoldan K, Ishaque N, Gu Z, Jechow K, Wieland D, Conrad C, Eils R, Fauvelle C, Baumert TF, Emmerich F, Bengsch B, Neumann-Haefelin C, Hofmann M, Thimme R, Boettler T. Follicular T helper cells shape the HCV-specific CD4+ T cell repertoire after virus elimination. J Clin Invest 2020;130(2):998-1009
  9. Tauber C, Schultheiss M, Luca R, Buettner N, Llewellyn-Lacey S, Emmerich F, Zehe S, Price DA, Neumann-Haefelin C, Schmitt-Graeff A, Hofmann M, Thimme R. Inefficient induction of circulating TAA-specific CD8+ T-cell responses in hepatocellular carcinoma. Oncotarget 2019;10(50):5194-5206
  10. Jacobi FJ*, Wild K*, Smits M, Zoldan K, Csernalabics B, Flecken T, Lang J, Ehrenmann P, Emmerich F, Hofmann M, Thimme R, Neumann-Haefelin C, Boettler T. OX40 stimulation and PD-L1 blockade synergistically augment HBV-specific CD4 T cells in patients with HBeAg-negative infection. J Hepatol 2019 Jun;70(6):1103-1113
  11. Kemming J*, Reeves E*, Nitschke K, Widmeier V, Emmerich F, Hermle T, Gostick E, Walker A, Timm J, Price DA, Hofmann M, Thimme R, James E*, Neumann-Haefelin C*. ERAP1 allotypes shape the epitope repertoire of virus-specific CD8+ T cell responses in acute hepatitis C virus infection. J Hepatol 2019;70(6):1072-1081
  12. Karimzadeh H*, Kiraithe MM*, Oberhardt V*, Salimi Alizei E, Bockmann J, Schulze Zur Wiesch J, Budeus B, Hoffmann D, Wedemeyer H, Cornberg M, Krawczyk A, Rashidi-Alavijeh J, Rodríguez-Frías F, Casillas R, Buti M, Smedile A, Alavian SM, Heinold A, Emmerich F, Panning M, Gostick E, Price DA, Timm J, Hofmann M, Raziorrouh B, Thimme R, Protzer U, Roggendorf M*, Neumann-Haefelin C*. Mutations in Hepatitis D Virus Allow It to Escape Detection by CD8<sup>+</sup> T Cells and Evolve at the Population Level. Gastroenterology 2019;156(6):1820-1833.
  13. Schuch A, Salimi Alizei E, Heim K, Wieland D, Kiraithe MM, Kemming J, Llewellyn-Lacey S, Sogukpinar Ö, Ni Y, Urban S, Zimmermann P, Nassal M, Emmerich F, Price DA, Bengsch B, Luxenburger H, Neumann-Haefelin C, Hofmann M, Thimme R. Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load. Gut 2019;68(5):905-915
  14. Schuch A, Zecher BF, Müller PA, Correia MP, Daul F, Rennert C, Tauber C, Schlitt K, Boettler T, Neumann-Haefelin C, Hengel H, Pircher H, Cerwenka A, Thimme R, Hofmann M. NK-cell responses are biased towards CD16-mediated effector functions in chronic hepatitis B virus infection. J Hepatol. 2019 Mar;70(3):351-360