The major focus of our lab is on innate immunity and inflammation, with projects ranging from molecular mechanisms of signal transduction to translational aspects of drug development. We explore how innate immune cells recognize and respond to pathogens, how genetic mutations in innate immunity contribute to inflammatory and auto-immune diseases, and how obtained information can be used to develop novel therapeutic strategies.
Toll-like receptor (TLR) signaling
TLRs represent a key family of pathogen recognition receptors that alert the immune system upon pathogen encounter via inflammation. We use proteomic approaches (quantitative mass spectrometry) to identify novel components of TLR signaling pathways, whose function we explore in vitro and in vivo.
Inflammatory Diseases (Lupus, Psoriasis)
We established novel mouse models based on human genetic information for the inflammatory diseases systemic lupus erythematosus and psoriasis. We use these models to explore the pathogenic mechanisms involved in order to identify direly needed novel therapeutic targets.
Generation of conditionally immortalized hematopoietic progenitors
We are using regulated Hox-genes to target and immortalize distinct hematopoietic progenitor cells, which can be used to explore cell differentiation and immune effector functions in vitro and in vivo. We are using this system primarily as a tool to study innate immune cell biology and cell differentiation.
We are using a novel phenotypic screening platform that we established recently to identify small molecule compounds for treatment of inflammatory diseases.
- Tawaratsumida K, Redecke V, Wu R, Kuriakose J, Bouchard JJ, Mittag T, Lohman BK, Mishra A, High AA, Häcker H.A phospho-tyrosine-based signaling module using SPOP, CSK, and LYN controls TLR-induced IRF activity.Science Advances 2022 Jul 8;8(27):eabq0084. doi: 10.1126/sciadv.abq0084. Epub 2022 Jul 8. PMID: 35857476 PMCID: PMC9269885.
- Redecke V, Tawaratsumida K, Larragoite ET, Williams ESCP, Planelles V, Spivak AM, Hirayama L, Elgort M, Swenson S, Smith R, Worthen B, Zimmerman R, Slev P, Cahoon B, Astill M, Häcker H. A rapid and affordable point of care test for antibodies against SARS-CoV-2 based on hemagglutination and artificial intelligence interpretation. Sci Rep. 2021 Dec 30;11(1):24507. doi: 10.1038/s41598-021-04298-1. PubMed PMID: 34969960; PubMed Central PMCID: PMC8718524.
- Gölling V, Tomas L, Weinberger T, Fischer M, Liu L, Wagner F, Lorenz M, Stark K, Häcker H, Schmidt-Supprian M, Völker U, Jastroch M, Lauber K, Straub T, Walzog B, Hammer E, Schulz C. Differences in Cell-Intrinsic Inflammatory Programs of Yolk Sac and Bone Marrow Macrophages. Cells. 2021 Dec 17;10(12). doi: 10.3390/cells10123564. PubMed PMID: 34944072; PubMed Central PMCID: PMC8699930.
- Piperno GM, Naseem A, Silvestrelli G, Amadio R, Caronni N, Cervantes-Luevano KE, Liv N, Klumperman J, Colliva A, Ali H, Graziano F, Benaroch P, Haecker H, Hanna RN, Benvenuti F. (2020) Wiskott-Aldrich syndrome protein restricts cGAS/STING activation by dsDNA immune complexes. JCI Insight. 5(17):e132857.
- Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt M. (2020) Microtubules control cellular shape and coherence in amoeboid migrating cells. J Cell Biol. 219(6):e201907154.
- Kuriakose J, Redecke V, Guy C, Zhou J, Wu R, Ippagunta SK, Tillman H, Walker PD, Vogel P, Häcker H (2019). Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis. J Clin Invest, 129(6):2251-2265.
- Ippagunta SK, Pollock JA, Sharma N, Lin W, Chen T, Tawaratsumida K, High AA, Min J, Chen Y, Guy RK, Redecke V, Katzenellenbogen JA, Häcker H (2018). Identification of Toll-like receptor signaling inhibitors based on selective activation of hierarchically acting signaling proteins. Sci Signal, 11(543):eaaq1077.
- Ippagunta SK, Gangwar R, Finkelstein D, Vogel P, Pelletier S, Gingras S, Redecke V, Häcker H (2016). Keratinocytes contribute intrinsically to psoriasis upon loss of Tnip1 function. Proc Natl Acad Sci U S A, 113(41), E6162-E6171
- Redecke V, Chaturvedi V, Kuriakose J, Häcker H (2016). SHARPIN controls the development of regulatory T cells. Immunology, 148(2), 216-26.
- Tawaratsumida K, Phan V, Hrincius ER, High AA, Webby R, Redecke V, Häcker H (2014). Quantitative proteomic analysis of the influenza A virus nonstructural proteins NS1 and NS2 during natural cell infection identifies PACT as an NS1 target protein and antiviral host factor. J Virol, 88(16), 9038-48.
- Redecke V, Wu R, Zhou J, Finkelstein D, Chaturvedi V, High AA, Häcker H (2013). Hematopoietic progenitor cell lines with myeloid and lymphoid potential. Nat Methods, 10(8), 795-803.
- Häcker H, Chi L, Rehg JE, Redecke V (2012). NIK prevents the development of hypereosinophilic syndrome-like disease in mice independent of IKKalpha activation. J Immunol, 188(9), 4602-10.
- Stempin CC, Chi L, Giraldo-Vela JP, High AA, Häcker H, Redecke V (2011). The E3 ubiquitin ligase mind bomb-2 (MIB2) protein controls B-cell CLL/lymphoma 10 (BCL10)-dependent NF-kappaB activation. J Biol Chem, 286(43), 37147-57.
- Zhou J, Wu R, High AA, Slaughter CA, Finkelstein D, Rehg JE, Redecke V, Häcker H (2011). A20-binding inhibitor of NF-kappaB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein beta activation and protects from inflammatory disease. Proc Natl Acad Sci U S A, 108(44), E998-1006.
- Häcker H, Redecke V, Blagoev B, Kratchmarova I, Hsu LC, Wang GG, Kamps MP, Raz E, Wagner H, Häcker G, Mann M, Karin M (2006). Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature, 439(7073), 204-7.
- Häcker H, Furmann C, Wagner H, Häcker G (2002). Caspase-9/-3 activation and apoptosis are induced in mouse macrophages upon ingestion and digestion of Escherichia coli bacteria. J Immunol, 169(6), 3172-9.
- Häcker H, Vabulas RM, Takeuchi O, Hoshino K, Akira S, Wagner H (2000). Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. J Exp Med, 192(4), 595-600.
- Häcker H, Mischak H, Hacker G, Eser S, Prenzel N, Ullrich A, Wagner H (1999). Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells. EMBO J, 18(24), 6973-82.
- Häcker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H (1998). CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J, 17(21), 6230-40.
- Häcker H, Tseng PH, Karin M (2011). Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol, 11(7), 457-68.
- Häcker H, Karin M (2006). Regulation and function of IKK and IKK-related kinases. Sci STKE, 2006(357), re13.