Head


Falk Weih
Falk Weih

Staff Scientists

Debra Weih (histology)

Postdocs

Ronny Hänold

Marc Riemann

Anja Weidemann

PhD Students

Nico Andreas

Christian Engelmann

Ievgen Oleksandrovich Koliesnik

Diploma Students

Engineers

Anne Gompf

Technicians

Elke Meier

Heike Dittmar (FACS)



 

Weih Research Group

Falk Weih

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Immunology

The NF-κB signal transduction pathway in development and dysfunction of the immune system

The Rel/NF-κB transcription factors play a pivotal role in immune responses, inflammation/autoimmunity, the regulation of apoptosis, and in cancer. With the help of genetically altered mouse models we are analyzing the NF-κB signaling pathway in both normal development and pathological alterations of the immune system, focusing on the recently described alternative activation pathway. One of our goals is a better understanding of NF-κB function in age-related immune deficiencies and disease.

 

Activation of NF-κB by the alternative (left)

Figure 1. Activation of NF-κB by the alternative (left) and the classical pathway (right). Signaling through TNFR, IL-1R, or Toll-like receptors (TLR) activates the classical NF-κB pathway involving predominantly the β and γ subunits of the IKK complex. Nuclear translocation and DNA-binding of p50-RelA heterodimers is accomplished through IκBα phosphorylation and ubiquitin-dependent proteasomal degradation. Membrane-bound LTα1β2, CD40, and BAFF, on the other hand, activate via their respective receptors the kinases NIK and IKKα. Phosphorylation of p100 results in the processing of the precursor to the p52 subunit and nuclear accumulation of p52-RelB heterodimers. There is significant cross talk since signaling through the LTβR, for instance, also results in the induction of RelA complexes. It is believed that the two pathways activate distinct sets of genes.

 

 

 

 

 

 

Projects

  • Regulation of lymphoid organ development by the NF-κB signaling pathway
  • Development and function of natural killer T cells and γδ T cells
  • Regulation of early B cell development by NF-κB
  • Tertiary lymphoid organs in atherosclerosis
  • Role of NF-κB in neurodegeneration and neuroprotection

 

Recent selected publications

  • Ben-Abdallah M, Sturny-Leclère A, Avé P, Louise A, Moyrand F, Weih F, Janbon G, Mémet S (2012) Fungal-induced cell cycle impairment, chromosome instability and apoptosis via differential activation of NF-κB. PLoS Pathogens, 8, e1002555. [PubMed]
  • Haenold R, Herrmann KH, Schmidt S, Reichenbach JR, Schmidt KF, Löwel S, Witte OW, Weih F, Kretz A (2012) Magnetic resonance imaging of the mouse visual pathway for in vivo studies of degeneration and regeneration in the CNS. Neuroimage, 59, 363-376. [PubMed]
  • Hamidi T, Algül H, Cano CE, Sandi MJ, Molejon MI, Riemann M, Calvo EL, Lomberk G, Dagorn JC, Weih F, Urrutia R, Schmid RM, Iovanna JL (2012) Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis. J Clin Invest, 122, 2092-2103. [PubMed]
  • Seo Y, Fukushima H, Maruyama T, Kuroishi KN, Osawa K, Nagano K, Aoki K, Weih F, Doi T, Zhang M, Ohya K, Katagiri T, Hosokawa R, Jimi E (2012) Accumulation of p100, a precursor of NF-κB2, enhances osteoblastic differentiation in vitro and bone formation in vivo in aly/aly mice. Mol Endocrinol, 26, 414-422. [PubMed]
  • Weih F, Gräbner R, Hu D, Beer M and Habenicht AJR (2012) Control of dichotomic innate and adaptive immune responses by artery tertiary lymphoid organs in atherosclerosis. Front Physio, 3, 226. [Journal]
  • Azukizawa H, Döhler A, Kanazawa N, Nayak A, Lipp M, Malissen B, Autenrieth I, Katayama I, Riemann M, Weih F, Berberich-Siebelt F, Lutz MB (2011) Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction of antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells. Eur J Immunol, 41, 1420-1434. [PubMed]
  • Powolny-Budnicka I, Riemann M, Tänzer S, Schmid RM, Hehlgans T, Weih F (2011) RelA and RelB transcription factors in distinct thymocyte populations control lymphotoxin-dependent interleukin-17 production in γδ T cells. Immunity, 34, 364-374. [PubMed]
  • Schneider G, Henrich A, Greiner G, Wolf V, Lovas A, Wieczorek M, Wagner T, Reichardt S, von Werder A, Schmid RM, Weih F, Heinzel T, Saur D, Krämer OH (2010) Cross talk between stimulated NF-kappaB and the tumor suppressor p53. Oncogene, 29, 2795-2806. [PubMed]
  • Saidi A, Li T, Weih F, Concannon P, Wang ZQ (2009) Dual functions of Nbs1 in the repair of DNA breaks and proliferation ensure proper V(D)J recombination and T-cell development. Mol Cell Biol, 30, 5572-5581. [PubMed]
  • Maruyama T, Fukushima H, Nakao K, Shin M, Yasuda H, Weih F, Doi T, Aoki K, Alles N, Ohya K, Hosokawa R, Jimi E (2009) Processing of the NF-κB2 precursor, p100, to p52 is critical for RANKL-induced osteoclast differentiation. J Bone Miner Res, 25, 1058-1067. [PubMed]
  • Soysa NS, Alles N, Weih D, Lovas A, Mian AH, Shimokawa H, Yasuda H, Weih F, Jimi E, Ohya K, Aoki K (2009) The pivotal role of the alternative NF-κB pathway in maintenance of basal bone homeostasis and osteoclastogenesis. J Bone Miner Res, 25, 809-818. [PubMed]
  • Lötzer K, Döpping S, Connert S, Gräbner R, Spanbroek R, Lemser B, Beer M, Hildner M, Hehlgans T, van der Wall M, Mebius RE, Lovas A, Randolph GJ, Weih F*, Habenicht AJR* (2009) Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizer-like cells upon combined TNFR1/LTβR NF-κB signaling. Arterioscler Thromb Vasc Biol, 30, 395-402. [PubMed] *equal contribution
  • Gräbner R, Lötzer K, Döpping S, Hildner M, Radke D, Beer M, Spanbroek R, Lippert B, Reardon DR, Getz GS, Fu YK, Hehlgans T, Mebius RE, van der Wall M, Kruspe D, Englert C, Lovas A, Hu D, Randolph GJ, Weih F, Habenicht AJR (2009) Lymphotoxin β receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice. J Exp Med, 206, 233-248. [PubMed]
  • Lovas A, Radke D, Albrecht D, Yilmaz ZB, Möller U, Habenicht AJR, Weih F (2008) Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts. BMC Genomics, 9, 606. [PubMed]
  • Dos Santos NR, Williame M, Gachet S, Cormier F, Janin A, Weih D, Weih F, Ghysdael J (2008) RelB-dependent stromal cells promote T-cell leukemogenesis. PLoS One, 3, e2555. [PubMed]
  • Guo F, Tänzer S, Busslinger M, Weih F (2008) Lack of NF-κB2/p100 causes a RelB-dependent block in early B lymphopoiesis. Blood, 112, 551-559. [PubMed]
  • Vallabhapurapu S, Powolny-Budnicka I, Riemann M, Schmid RM, Paxian S, Pfeffer K, Körner H, Weih F (2008) Rel/NF-κB family member RelA regulates NK1.1- to NK1.1+ transition as well as IL-15-induced expansion of NKT cells. Eur J Immunol, 38, 3508-3519. [PubMed]
  • Voelcker V, Gebhardt C, Averbeck M, Saalbach A, Wolf V, Weih F, Sleeman J, Anderegg U, Simon J (2008) Hyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signalling via TLR4. Exp Dermatol, 17, 100-107. [PubMed]
  • Balogh P, Balázs M, Czömpöly T, Weih DS, Arnold HH, Weih F (2007) Distinct roles of lymphotoxin-β signaling and the homeodomain transcription factor Nkx2.3 in the ontogeny of endothelial compartments in spleen. Cell Tissue Res, 328, 473-486. [PubMed]
  • Freyschmid EJ, Mathias CB, MacArthur DH, Laouar A, Narasimhaswamy M, Weih F, Oettgen HC (2007) Skin inflammation in RelB-/- mice leads to defective immunity and impaired viral clearance of vaccinia virus. J Allergy Clin Immunol, 119, 671-679. [PubMed]
  • Guo F, Weih D, Meier E, Weih F (2007) Constitutive alternative NF-κB signaling promotes marginal zone B cell development but disrupts the marginal sinus and induces HEV-like structures in the spleen. Blood, 110, 2381-2389. [PubMed]
  • Lo JC, Basak S, James ES, Quiambo RS, Kinsella MC, Alegre ML, Weih F, Franzoso G, Hoffmann A, Fu YX (2006) Coordination between NF-κB family members p50 and p52 is essential for mediating LTβR signals in the development and organization of secondary lymphoid tissues. Blood, 107, 1048-1055. [PubMed]
  • Zhang W, Potrovita I, Tarabin V, Herrmann O, Beer V, Weih F, Schneider A, Schwaninger M (2005) Neuronal activation of NF-κB contributes to cell death in cerebral ischemia. J Cereb Blood Flow Metab, 25, 30-40. [PubMed]
  • Sivakumar V, Hammond KJ, Howells N, Pfeffer K, Weih F (2003) Differential requirement for Rel/nuclear factor κB family members in natural killer T cell development. J Exp Med, 197, 1613-1621. [PubMed]
  • Weih F, Caamaño J (2003) Regulation of secondary lymphoid organ development by the nuclear factor-κB signal transduction pathway. Immunol Rev, 195, 91-105. [PubMed]
  • Yilmaz ZB, Weih DS, Sivakumar V, Weih F (2003) RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF. EMBO J, 22, 121-130. [PubMed]
  • Weih DS, Yilmaz ZB, Weih F (2001) Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J Immunol, 167, 1909-1919. [PubMed]
  • Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, Schwaninger M (1999) NF-κB is activated and promotes cell death in focal cerebral ischemia. Nat Med, 5, 554-559. [PubMed]
  • Weih F, Durham SK, Barton DS, Sha WC, Baltimore D, Bravo R (1997) p50-NF-κB complexes partially compensate for the absence of RelB: severely increased pathology in p50-/-relB-/- double-knockout mice. J Exp Med, 185, 1359-1370. [PubMed]
  • Weih F, Carrasco D, Durham SK, Barton DS, Rizzo CA, Ryseck RP, Lira SA, Bravo R (1995) Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-κB/Rel family. Cell, 80, 331-340. [PubMed]

 


Last update: February 4, 2014

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