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Hans Haecker Lab

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.



Hans Haecker MD, PhD

Professor Microbiology & Immunology

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
phone 801-587-1507



We are located on the first floor of the Emma Eccles Jones Medical Research Building.
Visitor Parking Information



    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)‘.

    Model of the TLR signal pathway

    Key publications:

    Zhou, PNAS, 2011 (PMID: 22011580)
    Ippagunta, PNAS, 2016 (PMID: 27671649)
    Kuriakose, JCI, 2019  (PMID: 31033479)


    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

    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.

    lupus and psoriasis figures

    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).

    Conditional Hox gene diagram

    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.

    Hematopoiesis model and lineage potential diagram

    Key publications:

    Wang, Nature Methods, 2006 (PMID: 16554834)
    Redecke,  Nature Methods,  2013 (PMID: 23749299)


    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.

    Drug Development of anti-inflammatory Toll-like receptor inhibitors models

    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 Invest130.
      • 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 Signal11(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 A113(41), E6162-E6171
      • Redecke V, Chaturvedi V, Kuriakose J, Häcker H (2016). SHARPIN controls the development of regulatory T cells. Immunology148(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 Virol88(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 Methods10(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 Immunol188(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 Chem286(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 A108(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. Nature439(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 Immunol169(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 Med192(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 J18(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 J17(21), 6230-40.


      • Häcker H, Tseng PH, Karin M (2011). Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol11(7), 457-68.
      • Häcker H, Karin M (2006). Regulation and function of IKK and IKK-related kinases. Sci STKE2006(357), re13.

      Lab Members

      Hans Haecker MD, PhD

      Professor Microbiology & Immunology

      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
      Phone:  801-587-1507

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      Vanessa Redecke MD, PhD

      Research Assistant Professor

      MD, PhD University of Luebeck, Germany
      Postdoc University of California, San Diego
      Assistant Member/ Staff Scientist St Jude Children’s Research Hospital, Memphis
      Phone:  801-213-8507

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      Kazuki Tawaratsumida, PhD

      Research Associate

      PhD Kagoshima University, Japan
      Postdoc St Jude Children’s Research Hospital, Memphis
      Phone:  801-585-6711

      Daniel J. Doty, BS

      Sr. Laboratory Specialist

      BS University of Utah
      Phone:  801-585-6711

      Feroz Shaik, PhD

      Postdoctoral Fellow

      PhD: University of Manitoba, Winnipeg, Canada
      Postdoc: University of Utah, Salt Lake City, U.S.
      Phone:  801-585-6711

      Shaheer Ahmad

      Postdoctoral Fellow

      Phone:  801-585-6711

      Faraz Salehi

      Graduate Student

      MS Shahid Beheshti University, Tehran, Iran
      Phone:  801-585-6711

      Malak Anees (Angel) Alsammarraie

      Undergraduate Student

      University of Utah (Major: Biology)
      Phone:  801-585-6711


      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

      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


      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 BiologyBiological Chemistry).

      If interested, please contact Dr. Hans Haecker at