Welcome to the Iowa Inflammation Program
1973 - B.S., Biology, State University of New York
1981 - Ph.D., Microbiology, New York University
Athmane Teghanemt, Ph. D. RAIII
De-Sheng Zhang, Ph.D., RA III
"Innate host responses to invading bacteria"
Defense of all multi-cellular organisms from invading microbes depends on evolutionarily conserved systems that recognize and respond to highly conserved and unique microbial structures. The innate immune systems of the host include a broad array of proteins that together couple microbial recognition to activation of inflammation, killing and elimination of microbes and their remnants, and return of the host to a normal resting state. Our work concerns: 1) the molecular basis of microbial recognition by specific human innate defense proteins; 2) how this recognition is linked to specific cellular outcomes (e.g. activation (or de-activation) of host cells, elimination of viable microbes and their remnants); and 3) how the mobilization and function of these host proteins are regulated to permit an appropriate evolution of host responses to infection.
In addition, we make use of the experimental setting of bacterial attack by defined host defense proteins to study the molecular bases of bacterial stress responses to sub-lethal injury and, in particular, repair of membrane damage. We hope these studies will provide new insights on the maintenance and regulation of (bacterial) membrane homeostasis and identify new targets for antibiotic development
Yang D, Postnikov YV, Li Y, Tewary P, de la Rosa G, Wei F, Klinman D, Gioannini T, Weiss JP, Furusawa T, Bustin M, Oppenheim JJ. High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses. J Exp Med. 2011 Dec 19. [Epub ahead of print]
Piazza M, Calabrese V, Damore G, Cighetti R, Gioannini T, Weiss J, Peri F. A synthetic Lipid A mimetic modulates human TLR4 activity. ChemMedChem. 2011 Dec 2. doi: 10.1002/cmdc.201100494 [Epub ahead of print]
Guinan EC, Barbon CM, Kalish LA, Parmar K, Kutok J, Mancuso CJ, Stoler-Barak L, Suter EE, Russell JD, Palmer CD, Gallington LC, Voskertchian A, Vergilio JA, Cole G, Zhu K, D'Andrea A, Soiffer R, Weiss JP, Levy O. (2011) Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death. Sci Transl Med. 2011 Nov 23;3(110):110ra118.
Esparza GA, Teghanemt A, Zhang D, Gioannini T.L., Weiss JP. Endotoxin•albumin complexes transfer endotoxin monomers to MD-2 resulting in activation of TLR4. Innate Immun. 2011 Oct 12. [Epub ahead of print]
Koprivnjak T, Zhang D, Ernst CM, Peschel A, Nauseef WM, Weiss JP. (2011) Characterization of Staphylococcus aureus cardiolipin synthases 1 and 2 and their contribution to accumulation of cardiolipin in stationary phase and within phagocytes. J Bacteriol. 193:4134-42.
Krasity BC, Troll JV, Weiss JP, McFall-Ngai MJ. (2011) LBP/BPI proteins and their relatives: conservation over evolution and roles in mutualism. Biochem Soc Trans. 39:1039-44
Palmer CD, Mancuso CJ, Weiss JP, Serhan CN, Guinan EC, Levy O. (2011) 17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and live E. coli. J Leukoc Biol. 90:459-70.
Piazza M, Colombo M, Zanoni I, Granucci F, Tortora P, Weiss J, Gioannini, T, Prosperi D, Peri F. (2011) Uniform Lipopolysaccharide (LPS)-Loaded Magnetic Nanoparticles for the Investigation of LPS-TLR4 Signaling. Angew Chem Int Ed Engl. 50:622-626.
Piazza, M., Calabrese, V., Baruffa, C., Gioannini, T., Weiss, J. and Peri, F. (2010) The cationic amphiphile 3,4-bis(tetradecyloxy)benzylamine inhibits LPS signaling by competing with endotoxin for CD14 binding. Biochem. Pharmacol. 80:2050-2056.
Piazza, M., Damore, G., Costa, B. Gioannini, T.L., Weiss, J.P. and Francesco Peri (2010) Hemin and a metabolic derivative coprohemin modulate the TLR4 pathway differently through different molecular targets. Innate Immunity, 17:293-301.
Prohinar, P., Rallabhandi, P., Weiss, J.P., Gioannini, T.L. (2010) Expression of functional D299G.T399I polymorphic variant of Toll-like receptor 4 (TLR4) depends more on co-expression of MD-2 than does wild-type TLR4. J. Immunol. 184:4362-4367.
Schwartz J, Leidal KG, Femling JK, Weiss JP, Nauseef WM. (2009) Neutrophil bleaching of GFP-expressing staphylococci: probing the intraphagosomal fate of individual bacteria. J Immunol. 183:2632-41.
Barker JH, McCaffrey RL, Baman NK, Allen LA, Weiss JP, Nauseef WM. (2009) The role of complement opsonization in interactions between F. tularensis subsp. novicida and human neutrophils. Microbes Infect. 11:762-9.
Vasl J, Oblak A, Gioannini TL, Weiss JP, Jerala R. (2009) Novel roles of lysines 122, 125, and 58 in functional differences between human and murine MD-2. J Immunol. 183:5138-45.
Piazza M, Yu L, Teghanemt A, Gioannini T, Weiss J, Peri F. (2009) Evidence of a specific interaction between new synthetic antisepsis agents and CD14. Biochemistry 48:12337-44.
Resman N, Vasl J, Oblak A, Pristovsek P, Gioannini TL, Weiss JP, Jerala R (2009) Essential roles of hydrophobic residues in both MD-2 and toll-like receptor 4 in activation by endotoxin. J. Biol. Chem. 284: 15052-15060.
Trompette A, Divanovic S, Visintin A, Blanchard C, Hegde RS, Madan R, Thorne PS, Wills-Karp M, Gioannini TL, Weiss JP, Karp CL. (2009) Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature, 457(7229):585-8.
Teghanemt, A., Widstrom, R.L., Gioannini, T.L. and Weiss J.P. (2008) “Isolation of monomeric and dimeric secreted (s)MD-2: Endotoxin.sCD14 and toll-like receptor 4 ectodomain selectively react with the monomeric form of sMD-2” J. Biol. Chem. 283:21881-9.
Vasl, J., Prohinar, P, Gioannini, T.L., Weiss, J.P. and Jerala, R. (2008) “Functional activity of MD-2 polymorphic variant Is significantly different in soluble and TLR4-bound forms: decreased endotoxin binding by G56R MD-2 and Its rescue by TLR4 ectodomain” J. Immunol. 180. 6107-6115.
Hadina S, Weiss JP, McCray PB Jr, Kulhankova K, Thorne PS. (2008) MD-2-dependent pulmonary immune responses to inhaled lipooligosaccharides: effect of acylation state. Am J Respir Cell Mol Biol. 38:647-54..