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Address: 51 Newton Road, 4-403 BSB Iowa City, IA 52242
Dr. Theresa Gioannini lost her battle with multiple myeloma on Saturday, January 4, 2014.
Gioannini received a B.S. in Chemistry from St. Mary-of-the-Woods
College in 1971 and an M.S. and Ph.D. in Chemistry from New York
University in 1976 and 1978. Dr. Gioannini began her career at New York
University and Buruch College, earning the rank of Full Professor at
Buruch College in 1993 prior to her academic career at the University of
Iowa.In 1998, she and Jerrold Weiss joined the Inflammation Program in
Internal Medicine and was granted the position of Adjunct Professor of
Biochemistry. For the last 15 years, Professor Gioannini contributed to
the Biochemistry undergraduate educational program and conducted research on toll-like receptors, most recently publishing in Nature and Innate Immunity. She will be greatly missed by colleagues, students and family.
Toll-like receptors couple molecular recognition of conserved and
structurally unique microbial molecules to rapid mobilization of innate
immune effector systems and subsequently induction of adaptive
immunity. Toll-like receptor 4 (TLR4) is essential for the recognition
of even minute amounts of endotoxin (E), unique
glycolipids abundantly present on the surface of Gram negative bacteria
(GNB). Variations in E structure – as occurs naturally among GNB – and
variations in levels of host cell proteins involved in E binding and
signal transduction make possible great diversification of host cell
responses to E.Efficientpotent
responses to E require the sequential action of extracellular and cell
surface host proteins: lipopolysaccharide-binding protein (LBP), CD14,
and MD-2 for delivery to and activation of TLR4. E-dependent responses
elicited through TLR4 lead to activation of either MyD88- and/or
TRIF-dependent signaling pathways. Novel reagents and experimental
approaches we have developed allow detection and quantitative analysis
of specific, high affinity (pM) E- protein and TLR4 interactions under
physiologically relevant conditions and have permitted further knowledge
of the mechanism of action of several natural and synthetic regulators
of TLR4 activation. Increasing evidence suggests physiologic and
patho-physiologic roles of TLR4 extending beyond host responses to
invading GNB. Our work is focused on understanding
Approaches to these questions utilize metabolically radiolabeled (or
[13C]-labeled) E and classical biochemical techniques, including the
preparation and purification of E-binding proteins and E:protein
complexes, to evaluate the nature and functional characteristics of
E:protein and protein:protein interactions involved in TLR4-dependent
responses. In collaboration with the NMR Facility, we have undertaken
the generation of isolated E:MD-2 complexes +/- TLR4 ectodomain as a
means to explore the variation in dynamics of E/MD-2/TLR4 interactions
of various complexes (agonist vs. antagonist E and mutant MD-2s) by
Teghanmet, A, Weiss, JP, Gioannini, TL. (2013)
Radioiodination of an endotoxin×MD-2 complex generates a novel
sensitive, high affinity ligand for TLR4. Innate Immunity Epub online
2013 Feb 25.
Rallabhandi P, Phillips, RL, Boukhvalova, MS, Pletneva, LM, Shirey, KA, Gioannini, TL,
Weiss, JP, Chow, JC, Hawkins, LD, Vogel, SN, Blanco, JC. (2012)
Respiratory syncytial virus fusion protein-Induced Toll-Like Receptor 4
(TLR4) signaling is inhibited by the TLR4 antagonists Rhodobacter
sphaeroides lipopolysaccharide and eritoran (E5564) and requires direct
interaction with MD-2. MBio. 2012 published online Aug 7;3(4). doi:
Wendlandt, EB, Graff, JW, Gioannini, TL, McCaffrey,
AP, Wilson, ME (2012) The role of microRNAs miR-200b and miR-200c in
TLR4 signaling and NF-kB activation. Innate Immunity 18:846-855.
Yu, L, Phillips, RL, Zhang, D, Teghanemt, A, Weiss, JP, Gioannini, TL.
(2012) NMR studies of hexaacylated endotoxin bound to wild-type and
F126A mutant MD-2 and MD-2•TLR4 ectodomain complexes. J. Biol. Chem.
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. (2012) High-mobility group
nucleosome-binding protein 1 acts as an alarmin and is critical for
lipopolysaccharide-induced immune responses. J. Exp. Med. 209:
Piazza, M, Calabrese, V, Damore, G, Cighetti, R, Gioannini, T, Weiss, J, Peri, F. (2012) A synthetic Lipid A mimetic modulates human TLR4 activity. ChemMedChem. 7: 213-217.
Esparza, GA, Teghanemt, A, Zhang, D, Gioannini, TL,Weiss,
JP (2012) Endotoxin•albumin complexes transfer endotoxin monomers to
MD-2 resulting in activation of TLR4. Innate Immunity 18:478-491.
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, TL, Weiss,
JP, and Peri, F. (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, JP, Gioannini, TL.
(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.
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.
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