Innate Immune Regulation – Quirin Hammer team

The team investigates molecular mechanisms that regulate innate immune cell responses.

Part of the:
Quirin Hammer team
Illustration of innate immune cells.
Illustration of the team's work on recognition of aberrant or virus-infected cells by innate immune cells. By: Quirin Hammer

Our research

The team explores signals that regulate the activation of immune cells with a focus on cytotoxic effector cells of the innate immune system as well as innate-like cells of the adaptive immune systems. Innate and innate-like lymphocytes with cytolytic properties such as natural killer (NK) cells and unconventional T cells represent the first line of defense against virus infections and developing cancers. Innate cells respond to a broad range of viruses and tumor cells using partly overlapping and partly very distinct pathways.

Central aspects of our research are to delineate the molecular signals that allow innate and innate-like lymphocytes to recognize virus-infected cells and to study by which means these innate cells discriminate between healthy and tumor-transformed cells. For this, we employ a broad range of in silico, cellular, as well as molecular biology techniques and study samples from patients with ongoing disease. In parallel to understanding the signals that initiate and restrict innate immune cell activation, we aim at exploiting such recognition pathways for cell therapy against cancer.

Collaborations

  • Professor Chiara Romagnani, German Rheumatism Reserach Center, Berlin, Germany.
  • Assistant Professor Amir Horowitz, Icahn School of Medicine at Mount Sinai, New York City, United States of America.
  • Associate Professor Mattia Mori, University of Siena, Siena, Italy.
  • Assistant Professor Francesco Spallotta, Institute for Systems Analysis and Computer Science “A. Ruberti”, Rome, Italy.
  • Professor Martin Messerle, Hannover Medical School, Hannover, Germany.
  • Professor Karl-Johan Malmberg, Karolinska Institutet, Stockholm, Sweden.

Research support

  • Marie Skłodowska-Curie Actions (EU)
  • Hedlunds Stiftelse
  • Groschinsky Minnesfond
  • Karolinska Institutet Foundation for Virus Reserach
  • Region Stockholm
  • Stiftelsen Lars Hiertas Minne
  • Petrus och Augusta Hedlunds Stiftelse
  • Stiftelsen Tornspiran
  • KI Foundations (KI stiftelser och fonder)
  • Åke Wibergs Stiftelse
  • Jonas Söderquist Scholarship

Publications

Selected publications

2020-2022

NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals.
Cuapio A, Boulouis C, Filipovic I, Wullimann D, Kammann T, Parrot T, Chen P, Akber M, Gao Y, Hammer Q, Strunz B, Pérez Potti A, Rivera Ballesteros O, Lange J, Muvva JR, Bergman P, Blennow O, Hansson L, Mielke S, Nowak P, Söderdahl G, Österborg A, Smith CIE, Bogdanovic G, Muschiol S, Hellgren F, Loré K, Sobkowiak MJ, Gabarrini G, Healy K, Sällberg Chen M, Alici E, Björkström NK, Buggert M, Ljungman P, Sandberg JK, Aleman S, Ljunggren HG
Mol Med 2022 02;28(1):20 

SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells.
Hammer Q, Dunst J, Christ W, Picarazzi F, Wendorff M, Momayyezi P, Huhn O, Netskar HK, Maleki KT, García M, Sekine T, Sohlberg E, Azzimato V, Aouadi M, , , Degenhardt F, Franke A, Spallotta F, Mori M, Michaëlsson J, Björkström NK, Rückert T, Romagnani C, Horowitz A, Klingström J, Ljunggren HG, Malmberg KJ
Cell Rep 2022 03;38(10):110503

An optimized platform for efficient siRNA delivery into human NK cells.
Palacios D, Momayyezi P, Huhn O, Ask EH, Dunst J, Malmberg KJ, Hammer Q
Eur J Immunol 2022 Apr;():

Extent of Cytomegalovirus Replication in the Human Host Depends on Variations of the HLA-E/UL40 Axis.
Vietzen H, Rückert T, Hartenberger S, Honsig C, Jaksch P, Geleff S, Hammer Q, Romagnani C, Segura-Wang M, Puchhammer-Stöckl E
mBio 2021 03;12(2):

Natural killer cell immunotypes related to COVID-19 disease severity.
Maucourant C, Filipovic I, Ponzetta A, Aleman S, Cornillet M, Hertwig L, Strunz B, Lentini A, Reinius B, Brownlie D, Cuapio A, Ask EH, Hull RM, Haroun-Izquierdo A, Schaffer M, Klingström J, Folkesson E, Buggert M, Sandberg JK, Eriksson LI, Rooyackers O, Ljunggren HG, Malmberg KJ, Michaëlsson J, Marquardt N, Hammer Q, Strålin K, Björkström NK,
Sci Immunol 2020 08;5(50):

TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells.
Sekine T, Perez-Potti A, Nguyen S, Gorin JB, Wu VH, Gostick E, Llewellyn-Lacey S, Hammer Q, Falck-Jones S, Vangeti S, Yu M, Smed-Sörensen A, Gaballa A, Uhlin M, Sandberg JK, Brander C, Nowak P, Goepfert PA, Price DA, Betts MR, Buggert M
Sci Immunol 2020 07;5(49):

NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells.
Babic M, Dimitropoulos C, Hammer Q, Stehle C, Heinrich F, Sarsenbayeva A, Eisele A, Durek P, Mashreghi MF, Lisnic B, Van Snick J, Löhning M, Fillatreau S, Withers DR, Gagliani N, Huber S, Flavell RA, Polic B, Romagnani C
J Exp Med 2020 08;217(8):

2018-2019

Remodeling of secretory lysosomes during education tunes functional potential in NK cells.
Goodridge JP, Jacobs B, Saetersmoen ML, Clement D, Hammer Q, Clancy T, Skarpen E, Brech A, Landskron J, Grimm C, Pfefferle A, Meza-Zepeda L, Lorenz S, Wiiger MT, Louch WE, Ask EH, Liu LL, Oei VYS, Kjällquist U, Linnarsson S, Patel S, Taskén K, Stenmark H, Malmberg KJ
Nat Commun 2019 01;10(1):514

Natural killer cell specificity for viral infections.
Hammer Q, Rückert T, Romagnani C
Nat Immunol 2018 08;19(8):800-808

Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells.
Hammer Q, Rückert T, Borst EM, Dunst J, Haubner A, Durek P, Heinrich F, Gasparoni G, Babic M, Tomic A, Pietra G, Nienen M, Blau IW, Hofmann J, Na IK, Prinz I, Koenecke C, Hemmati P, Babel N, Arnold R, Walter J, Thurley K, Mashreghi MF, Messerle M, Romagnani C
Nat Immunol 2018 05;19(5):453-463

Funding

Grants

  • Swedish Research Council
    1 January 2025 - 31 December 2028
    It is a natural occurrence that viruses and humans co-exist. Although the acute phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is behind us, the virus continues to evolve. This ongoing evolution poses a high risk for the emergence of variants, which undermine existing immunity. While considerable knowledge exists regarding antibody responses and T cells reactivity, the contribution of innate factors in protecting us against SARS-CoV-2 remains relatively unexplored. Moreover, it is still unknown whether SARS-CoV-2 evolves to escape from such innate immunity.The proposed project addresses this knowledge gap by decoding the interplay of SARS-CoV-2 evolution with host innate immunity and the consequences thereof on infection outcomes in patients. To this end, we will delineate whether mutations in emerging variants impact on recognition by innate natural killer (NK) cells. We will monitor the co-evolution of SARS-CoV-2 with NK cells in real time by leveraging computational methods and global databases. Finally, we seek to understand how this interplay influences infection outcomes in patients, potentially paving the way for precision medicine interventions.Collectively, successful implementation of the project will provide interdisciplinary insights that deepen our understanding of viral evolution and its impact on host innate immune responses. This may have important implications for patients and provide valuable insights for future pandemics.
  • KI Foundation for Virus Research 2021-2022
  • Petrus och Augusta Hedlunds Stiftelse 2021-2022
  • Clas Groschinskys Minnesfond 2021-2022
  • Stiftelsen Lars Hiertas Minne 2021-2022
  • Stiftelsen Tornspiran 2021-2023
  • Forskar-ST 2021-2025
    Region Stockholm
  • KI Foundation for Virus Research 2022-2023
  • Petrus och Augusta Hedlunds Stiftelse 2022-2023
  • Clas Groschinskys Minnesfond 2022-2023
  • KI Foundations 2022-2024
  • Åke Wibergs Stiftelse 2022-2024
  • KI Foundation for Virus Research 2023-2024
  • Stiftelsen Lars Hiertas Minne 2023-2024
  • Felix Mindus Foundation 2023-2024
  • Stiftelsen Tornspiran 2023-2024
  • KI Foundation for Virus Research 2024-2025
  • Jeanssons Stiftelser 2024-2026
  • KI Foundations 2024-2026
  • Åke Wibergs Stiftelse 2024-2026
  • Magnus Bergvall Stiftelse 2024-2025