Welcome to the Haecker Lab!
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.
- Drug Development. We are using a novel phenotypic screening platform that we established recently to identify small molecule compounds for treatment of inflammatory diseases.
Read more about our lab's research.
Contact Us
Department of Pathology
Division of Microbiology and Immunology
University of Utah
Emma Eccles Jones Medical Research Building
15 N. Medical Drive East, Rm 1520 H
Salt Lake City, UT 84112
email hans.haecker@path.utah.edu
phone 801-587-1507
We are located on the first floor of the Emma Eccles Jones Medical Research Building.
Visitor Parking Information
Research
Background:
TLRs represent a family of receptors essential for recognizing pathogens. They initiate signaling via adaptor proteins and partially defined pathways. TLRs upregulate inflammatory genes to initiate immune responses, however, exaggerated/ prolonged TLR activation can lead to inflammatory pathology.
Our major observations:
We identified/ characterized various components of these pathways, including MyD88 and TRAF6 as part of the TLR9 pathway (recognizing DNA), TRAF3 as regulator of interferons and IL-10, and ABIN1/TNIP1 as regulator of the C/EBPb pathway.
Project layout:
We use primarily artificial dimerization of adaptor proteins and affinity purification to characterize transiently assembled signaling complexes by quantitative mass spectrometry. We characterize identified proteins functionally in vitro and in vivo.
Current focus:
We explore the molecular mechanism of TNIP1 function, which is essential to protect us from inflammatory diseases. We also work on a new ‘signaling protein, which controls the transcription factor family‚ interferon regulatory factors (IRF)‘.
Key publications:
Zhou, PNAS, 2011 (PMID: 22011580)
Ippagunta, PNAS, 2016 (PMID: 27671649)
Kuriakose, JCI, 2019 (PMID: 31033479)
Background:
We indentified ABIN1/TNIP1 as component of the TLR signaling complex, which is essential to counteract pro-inflammatory TLR signaling. Human TNIP1 is genetically linked to the inflammatory diseases “systemic lupus erythematosus (SLE)“ and “psoriasis“ (hypomorphic polymorphisms). SLE is an “autoimmune“ disease of unclear etiology characterized by auto-antibodies and inflammatory infiltration of many organ systems. Immune complex-deposits in the kidneys are believed to drive glomerulonephritis leading to kidney failure. Psoriasis is an chronic, inflammatory skin disease, characterized by proliferating epidermal cells (keratinocytes), leading to red, scaling patches.
Our major
observations:
TNIP1-/- mice develop constitutively the major symptoms of human SLE and, inducibly, psoriasis-like disease. Consistent with current models, SLE is driven by nucleic acid-recognizing TLRs (TLR7/9, MyD88), while psoriasis is driven by the IL-17R.
Surprisingly, genetic deletion of T- and B-cells (and thus IgG) did not provide protection from kidney disease. In contrast, we found that a monocyte subtype (Patrolling monocytes, Pmo), accumulates in kidney glomeruli and, intruigingly, that genetic deletion of PMo protected from GN. As such, innate immune cells, not B-cell-derived auto-antibodies promote GN, suggesting a shift in paradigm with important ramnifications for human disease and therapeutic approaches.
Current project:
We explore the mechanism of patrolling monocyte (PMo) deregulation. We investigate why PMo are up-regulated (cell differentiation vs. survival) and study the contribution of C/EBPb to PMo deregulation and disease. We also investigate established and novel therapeutic strategies to prevent PMo- mediated disease.
Key publications:
Zhou, PNAS, 2011 (PMID: 22011580)
Ippagunta, PNAS, 2016 (PMID: 27671649)
Kuriakose, JCI, 2019 (PMID: 31033479)
Background and key observations:
Hox genes are developmentally important transcription factors. Constitutively active Hox-mutants are oncogenes. Estrogen-regulated Hox-genes can be used to block cell differentiation. The combination of regulated Hox-gene and specific growth factor can be used to immortalize specific progenitor cells with neutrophil potential (Hoxb8-SCF (SCF)) or multi-lineage potential (Hoxb8-FL, FLT3L)(see publication below).
Current projects:
- Conditional immortalization of an erythrocyte/ megakaryocate progenitor.
- Application of Hox-cells in various models, including inflammatory and infectious disease models to study cell differentiation and contribution of specific immune cell populations to immunity.
Key publications:
Wang, Nature Methods, 2006 (PMID: 16554834)
Redecke, Nature Methods, 2013 (PMID: 23749299)
Background:
TLR-mediated inflammation promotes a plethora of human diseases, including acute bacterial sepsis, chronic inflammatory diseases (e.g. SLE), cancer (e.g. certain lymphomas) and metabolic diseases, e.g. ischemia-reperfusion injury (cardiac infarction, stroke). Despite the obvious clinical need, no drugs are currently clinically available. This is –at least in part- due to the signaling mechanisms involved, which depend largely on protein interactions (highlighted with yellow dots in figure below). Such interactions are inherently difficult for targeted drug developmental approaches. In turn, while phenotypic approaches could be used, those have the disadvantage of the uncertainty of the drug target. To overcome this problem, we developed a novel phenotypic screening platform that relies on artificial activation of signaling proteins that act at different levels of the TLR pathway (green arrows in figure below). This allows us during the drug-screening campaign to focus on compounds that inhibit the TLR-specific signaling level (upstream of TRAF). We provided proof-of-concept for this approach in recent work.
Major observations:
We used a bioactive compound library and provided proof of concept for described signaling level-specific phenotypic drug screening. Moreover, using this approach we identifed a small molecule TLR signaling inhibitor scaffold (TSI), whose more detailed analysis related to structure activity relationship and mechanism of action demostrated intruiging properties.
Current projects:
We currently optimize described TSI scaffold, for further preclinical testing in in vivo inflammatory mouse models. We also initiated a more extensive HTS, in collaboration with the St. Jude Children‘s Research Hospital, to identify additional chemotypes for successful long-term drug development.
Key publications:
Ippagunta, Science Signaling, 2018 (PMID: 30108181)
Pollock, ChemMedChem, 2018 (PMID: 30117269)
Selected Publications
- 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.LID - 10.1172/JCI125116 [doi]LID - 125116 [pii]. J Clin Invest, 130.
- 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.LID - eaaq1077 [pii]LID - 10.1126/scisignal.aaq1077 [doi]. Sci Signal, 11(543).
- 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 signaling 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.
- 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. (Epub ahead of print) JCI Insight.
- Kuriakose J, Redecke V, Guy C, Zhou J, Wu R, Ippagunta SK, Tillman H, Walker PD, Vogel P, Hcker H (2019). Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis.LID - 10.1172/JCI125116 [doi]LID - 125116 [pii]. J Clin Invest, 130.
- Pollock JA, Sharma N, Ippagunta SK, Redecke V, Hcker H, Katzenellenbogen JA (2018). Triaryl Pyrazole Toll-Like Receptor Signaling Inhibitors: Structure-Activity Relationships Governing Pan- and Selective Signaling Inhibitors. ChemMedChem, 13(20), 2208-2216.
- Ippagunta SK, Pollock JA, Sharma N, Lin W, Chen T, Tawaratsumida K, High AA, Min J, Chen Y, Guy RK, Redecke V, Katzenellenbogen JA, Hcker H (2018). Identification of Toll-like receptor signaling inhibitors based on selective activation of hierarchically acting signaling proteins.LID - eaaq1077 [pii]LID - 10.1126/scisignal.aaq1077 [doi]. Sci Signal, 11(543).
- Leithner A, Renkawitz J, De Vries I, Hauschild R, Hcker H, Sixt M (2018). Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. Eur J Immunol, 48(6), 1074-1077.
- Yang CH, Wang Y, Sims M, Cai C, He P, Hcker H, Yue J, Cheng J, Boop FA, Pfeffer LM (2017). MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway. Oncotarget, 8(68), 112980-112991.
- Di Ceglie I, van den Akker GG, Ascone G, Ten Harkel B, Hcker H, van de Loo FA, Koenders MI, van der Kraan PM, de Vries TJ, Vogl T, Roth J, van Lent PL (2017). Genetic modification of ER-Hoxb8 osteoclast precursors using CRISPR/Cas9 as a novel way to allow studies on osteoclast biology. J Leukoc Biol, 101(4), 957-966.
- Penkert RR, Jones BG, Hcker H, Partridge JF, Hurwitz JL (2017). Vitamin A differentially regulates cytokine expression in respiratory epithelial and macrophage cell lines. Cytokine, 91, 1-5.
- Grajkowska LT, Ceribelli M, Lau CM, Warren ME, Tiniakou I, Nakandakari Higa S, Bunin A, Hcker H, Mirny LA, Staudt LM, Reizis B (2017). Isoform-Specific Expression and Feedback Regulation of E Protein TCF4 Control Dendritic Cell Lineage Specification. Immunity, 46(1), 65-77.
- Ippagunta SK, Gangwar R, Finkelstein D, Vogel P, Pelletier S, Gingras S, Redecke V, Hcker H (2016). Keratinocytes contribute intrinsically to psoriasis upon loss of Tnip1 function. Proc Natl Acad Sci U S A, 113(41), E6162-E6171.
- Kaewborisuth C, Zanin M, Hcker H, Webby RJ, Lekcharoensuk P (2016). G45R mutation in the nonstructural protein 1 of A/Puerto Rico/8/1934 (H1N1) enhances viral replication independent of dsRNA-binding activity and type I interferon biology. Virol J, 13, 127.
- Redecke V, Chaturvedi V, Kuriakose J, Hcker H (2016). SHARPIN controls the development of regulatory T cells. Immunology, 148(2), 216-26.
- Bunin A, Sisirak V, Ghosh HS, Grajkowska LT, Hou ZE, Miron M, Yang C, Ceribelli M, Uetani N, Chaperot L, Plumas J, Hendriks W, Tremblay ML, Hcker H, Staudt LM, Green PH, Bhagat G, Reizis B (2015). Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells. Immunity, 43(2), 277-88.
- Wache C, Klein M, Ostergaard C, Angele B, Hcker H, Pfister HW, Pruenster M, Sperandio M, Leanderson T, Roth J, Vogl T, Koedel U (2015). Myeloid-related protein 14 promotes inflammation and injury in meningitis. J Infect Dis, 212(2), 247-57.
- Tawaratsumida K, Phan V, Hrincius ER, High AA, Webby R, Redecke V, Hcker 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.
- Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, Schmitt-Graeff A, Freudenberg M, von Loewenich FD, Wolf P, Leonhardt F, Baxan N, Pfeifer D, Schmah O, Schonle A, Martin SF, Mertelsmann R, Duyster J, Finke J, Prinz M, Henneke P, Hcker H, Hildebrandt GC, Hcker G, Zeiser R (2014). Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med, 20(6), 648-54.
- Klein M, Brouwer MC, Angele B, Geldhoff M, Marquez G, Varona R, Hcker G, Schmetzer H, Hcker H, Hammerschmidt S, van der Ende A, Pfister HW, van de Beek D, Koedel U (2014). Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis. PLoS ONE, 9(4), e93057.
- Redecke V, Wu R, Zhou J, Finkelstein D, Chaturvedi V, High AA, Hcker H (2013). Hematopoietic progenitor cell lines with myeloid and lymphoid potential. Nat Methods, 10(8), 795-803.
- Gautam S, Kirschnek S, Gentle IE, Kopiniok C, Henneke P, Hcker H, Malleret L, Belaaouaj A, Hcker G (2013). Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-beta (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation. Cell Death Differ, 20(8), 1068-79.
- Hohne C, Wenzel M, Angele B, Hammerschmidt S, Hcker H, Klein M, Bierhaus A, Sperandio M, Pfister HW, Koedel U (2013). High mobility group box 1 prolongs inflammation and worsens disease in pneumococcal meningitis. Brain, 136(Pt 6), 1746-59.
- LeMessurier KS, Hcker H, Chi L, Tuomanen E, Redecke V (2013). Type I interferon protects against pneumococcal invasive disease by inhibiting bacterial transmigration across the lung. PLoS Pathog, 9(11), e1003727.
- Hcker 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.
- Zhou J, Wu R, High AA, Slaughter CA, Finkelstein D, Rehg JE, Redecke V, Hcker 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.
- Kirschnek S, Vier J, Gautam S, Frankenberg T, Rangelova S, Eitz-Ferrer P, Grespi F, Ottina E, Villunger A, Hcker H, Hcker G (2011). Molecular analysis of neutrophil spontaneous apoptosis reveals a strong role for the pro-apoptotic BH3-only protein Noxa. Cell Death Differ, 18(11), 1805-14.
- Stempin CC, Chi L, Giraldo-Vela JP, High AA, Hcker 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.
- Hcker H, Tseng PH, Karin M (2011). Expanding TRAF function: TRAF3 as a tri-faced immune regulator. [Review]. Nat Rev Immunol, 11(7), 457-68.
- Garrison SP, Thornton JA, Hcker H, Webby R, Rehg JE, Parganas E, Zambetti GP, Tuomanen EI (2010). The p53-target gene puma drives neutrophil-mediated protection against lethal bacterial sepsis. PLoS Pathog, 6(12), e1001240.
- LeMessurier K, Hcker H, Tuomanen E, Redecke V (2010). Inhibition of T cells provides protection against early invasive pneumococcal disease. Infect Immun, 78(12), 5287-94.
- Woehrl B, Klein M, Rupprecht T, Schmetzer H, Angele B, Hcker H, Hcker G, Pfister HW, Koedel U (2010). CXCL16 contributes to neutrophil recruitment to cerebrospinal fluid in pneumococcal meningitis. J Infect Dis, 202(9), 1389-96.
- Koedel U, Frankenberg T, Kirschnek S, Obermaier B, Hcker H, Paul R, Hcker G (2009). Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis. PLoS Pathog, 5(5), e1000461.
- Wang H, Matsuzawa A, Brown SA, Zhou J, Guy CS, Tseng PH, Forbes K, Nicholson TP, Sheppard PW, Hcker H, Karin M, Vignali DA (2008). Analysis of nondegradative protein ubiquitylation with a monoclonal antibody specific for lysine-63-linked polyubiquitin. Proc Natl Acad Sci U S A, 105(51), 20197-202.
- Into T, Inomata M, Nakashima M, Shibata K, Hcker H, Matsushita K (2008). Regulation of MyD88-dependent signaling events by S nitrosylation retards toll-like receptor signal transduction and initiation of acute-phase immune responses. Mol Cell Biol, 28(4), 1338-47.
- Frankenberg T, Kirschnek S, Hcker H, Hcker G (2008). Phagocytosis-induced apoptosis of macrophages is linked to uptake, killing and degradation of bacteria. Eur J Immunol, 38(1), 204-15.
- El Kasmi KC, Smith AM, Williams L, Neale G, Panopoulos AD, Watowich SS, Hcker H, Foxwell BM, Murray PJ (2007). Cutting edge: A transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway. J Immunol, 179(11), 7215-9.
- Hcker H, Karin M (2006). Regulation of IKK. In Handbook of Transcription Factor NF-kappaB (pp. 25-51). CRC Press.
- Hcker H, Karin M (2006). Regulation and function of IKK and IKK-related kinases. [Review]. Sci STKE, 2006(357), re13.
- Wang GG, Calvo KR, Pasillas MP, Sykes DB, Hcker H, Kamps MP (2006). Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8. Nat Methods, 3(4), 287-93.
- Hcker H, Redecke V, Blagoev B, Kratchmarova I, Hsu LC, Wang GG, Kamps MP, Raz E, Wagner H, Hcker 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.
- Kirschnek S, Ying S, Fischer SF, Hcker H, Villunger A, Hochrein H, Hcker G (2005). Phagocytosis-induced apoptosis in macrophages is mediated by up-regulation and activation of the Bcl-2 homology domain 3-only protein Bim. J Immunol, 174(2), 671-9.
- Amir RE, Hcker H, Karin M, Ciechanover A (2004). Mechanism of processing of the NF-kappa B2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase. Oncogene, 23(14), 2540-7.
- Redecke V, Hcker H, Datta SK, Fermin A, Pitha PM, Broide DH, Raz E (2004). Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma. J Immunol, 172(5), 2739-43.
- Seegmuller I, Hcker H, Wagner H (2003). IL-4 regulates IL-12 p40 expression post-transcriptionally as well as via a promoter-based mechanism. Eur J Immunol, 33(2), 428-33.
- Hcker H, Karin M (2002). Is NF-kappaB2/p100 a direct activator of programmed cell death? [Review]. Cancer Cell, 2(6), 431-3.
- Hcker H, Furmann C, Wagner H, Hcker 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.
- Ahmad-Nejad P, Hcker H, Rutz M, Bauer S, Vabulas RM, Wagner H (2002). Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol, 32(7), 1958-68.
- Hcker G, Redecke V, Hcker H (2002). Activation of the immune system by bacterial CpG-DNA. [Review]. Immunology, 105(3), 245-51.
- Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Hcker H, Wagner H (2001). Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem, 276(33), 31332-9.
- Bauer S, Kirschning CJ, Hcker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB (2001). Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci U S A, 98(16), 9237-42.
- Hcker 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.
- Vabulas RM, Pircher H, Lipford GB, Hcker H, Wagner H (2000). CpG-DNA activates in vivo T cell epitope presenting dendritic cells to trigger protective antiviral cytotoxic T cell responses. J Immunol, 164(5), 2372-8.
- Wagner H, Lipford GB, Hcker H (2000). The role of immunostimulatory CpG-DNA in septic shock. [Review]. Springer Semin Immunopathol, 22(1-2), 167-71.
- Wagner H, Hcker H, Lipford GB (2000). Immunostimulatory DNA sequences help to eradicate intracellular pathogens. [Review]. Springer Semin Immunopathol, 22(1-2), 147-52.
- Schrezenmeier H, Hildebrand A, Rojewski M, Hcker H, Heimpel H, Raghavachar A (2000). Paroxysmal nocturnal haemoglobinuria: a replacement of haematopoietic tissue? Acta Haematol, 103(1), 41-8.
- Hcker H (2000). Signal transduction pathways activated by CpG-DNA. [Review]. Curr Top Microbiol Immunol, 247, 77-92.
- Hcker 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.
- Hcker 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.
- Heeg K, Sparwasser T, Lipford GB, Hcker H, Zimmermann S, Wagner H (1998). Bacterial DNA as an evolutionary conserved ligand signalling danger of infection to immune cells. [Review]. Eur J Clin Microbiol Infect Dis, 17(7), 464-9.
- Sparwasser T, Miethke T, Lipford G, Erdmann A, Hcker H, Heeg K, Wagner H (1997). Macrophages sense pathogens via DNA motifs: induction of tumor necrosis factor-alpha-mediated shock. Eur J Immunol, 27(7), 1671-9.
- Sparwasser T, Miethke T, Lipford G, Borschert K, Hcker H, Heeg K, Wagner H (1997). Bacterial DNA causes septic shock. Nature, 386(6623), 336-7.
- del Val M, Hengel H, Hcker H, Hartlaub U, Ruppert T, Lucin P, Koszinowski UH (1992). Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment. J Exp Med, 176(3), 729-38.
Lab Members
Hans Haecker MD, PhD
MD University of Ulm, Germany
PhD Technical University Munich, Germany
Postdoc University of California, San Diego
Assistant/ Associate Member St. Jude Children’s Research Hospital, Memphis
Email: hans.haecker@path.utah.edu
Phone: 801-587-1507
Vanessa Redecke MD, PhD
MD, PhD University of Luebeck, Germany
Postdoc University of California, San Diego
Assistant Member/ Staff Scientist St Jude Children’s Research Hospital, Memphis
Email: vanessa.redecke@path.utah.edu
Phone: 801-213-8507
Kazuki Tawaratsumida, PhD
PhD Kagoshima University, Japan
Postdoc St Jude Children’s Research Hospital, Memphis
Email: kazuki.tawaratsumida@path.utah.edu
Phone: 801-585-6711
Feroz Shaik, PhD
PhD: University of Manitoba, Winnipeg, Canada
Postdoc: University of Utah, Salt Lake City, U.S.
Email: feroz.shaik@path.utah.edu
Phone: 801-585-6711
Faraz Salehi
MS Shahid Beheshti University, Tehran, Iran
Email: faraz.salehi@path.utah.edu
Phone: 801-585-6711
Malak Anees (Angel) Alsammarraie
University of Utah (Major: Biology)
Phone: 801-585-6711
Funding
NIH RO1
06/01/18 - 05/31/22
Discovery of small molecules inhibiting Toll-like receptor-mediated inflammation
Principal Investigator: Hans R. Haecker
National Institute of Allergy and Infectious Diseases
NIH/NIAID RO1
05/03/19 - 04/30/24
Pathogenic role of innate immune cells in lupus nephritis
Principal Investigator: Hans R. Haecker
National Institute of Allergy and Infectious Diseases
Collaborations
A key component of our lab culture are collaborations inside and outside of the lab.
Established collaborations
TLR signaling and inflammation
Dr. Patrick Walker, CEO Arkana Laboratories, Little Rock (kidney pathology in lupus patients)
Dr. Peter Vogel, Director Veterinary Pathology Core, Department of Pathology, St. Jude
Dr. Heather Tillman, Assistant Professor, Department of Pathology, St. Jude
Dr. Marc Barry, Associate Professor, Department of Pathology, University of Utah
Dr. James Cox, Director Mass Spectrometry & Proteomics, University of Utah
Dr. Cliff Guy, Managing Director, Imaging Facility Department of Immunology, St.Jude
TLR drug development
Dr. Taosheng Cheng, Director High through put screening (HTS) core, St. Jude
Dr. John Katzenellenbogen, Professor, University of Illinois, Urbana
Dr. Julie Pollock, Assistant Professor, Chemistry Department, University of Richmond
Dr. Richard Lee, Member, Department of Chemical Biology and Therapeutics, St. Jude
Conditionally immortalized hematopoietic progenitor cells
Dr. Thomas Vogl, Professor, Department of Immunology, University of Münster
Dr. Barbara Walzog, Professor, Department of Physiology, LMU Munich
Dr. Uwe Koedel, Professor, Department of exp. Neurology, LMU Munich
Dr. Michael Sixt, Professor, Institute of Science and Technology, Vienna
Dr. Georg Häcker, Director Inst. of Microbiology and Hygiene, University of Freiburg
Dr. Boris Reizis, Professor, Department of Pathology, New York University
Dr. Stephen Nutt, Professor, WEHI institute, Melbourne
Dr. Thomas Graf, Senior Scientist, Centre for Genomic Regulation, Barcelona
Dr. Philippe PIERRE, Professor, Centre d’Immunologie de Marseille-Luminy
Dr. Peter VanLent, Professor, Radboud University Medical Center, Nijmegen
Dr. Mortimer Poncz, Professor, University of Pennsylvania
Dr. Tobias Hohl, Chief, Infectious Diseases Service, Memorial Sloan Kettering, New York
Join Us
We are actively recruiting biochemists and immunologists for post-doctoral positions in the lab.
We are also recruiting graduate students with interest in inflammation biology and drug development. Please explore the current Graduate Programs at the University of Utah to see what is needed (Molecular Biology, Biological Chemistry).
If interested, please contact Dr. Hans Haecker at hans.haecker@path.utah.edu.