Fabio Re, Ph.D.

Associate Professor
Office: 2.343
Telephone: (847) 578-8650
Lab: 2.406A-F
Telephone: (847) 578-7706
E-mail: fabio.re@rosalindfranklin.edu


 

Biography

Fabio Re graduated from the University of Milan in 1989. In the lab of Dr. Alberto Mantovani at the Mario Negri Institute for Pharmacological Research he conducted studies on the role of the Interleukin-1 receptor type II that led to the concept of “decoy receptor”, a paradigm later found to apply to other cytokine systems.

In 1994 he moved to Columbia University, New York, in the lab of Dr. Jeremy Luban where he studied the effect of HIV infection on cell cycle progression.

In 1999 he joined the lab of Dr. Jack Strominger at the Dana-Farber Cancer Institute, Boston, where he studied several aspects of the biology of toll-like receptors (TLR), including the differential activation of dendritic cells by TLR agonists and the interaction of LPS with TLR4/MD-2. During this period he held an Instructor position in the Department of Pathology of the Harvard Medical School.

In 2004 he was appointed Assistant Professor in the Department of Molecular Sciences at the University of Tennessee Health Science Center in Memphis. His research efforts remained focused on innate immunity. He was tenured and promoted to Associate Professor in 2010.

In 2012 he joined the Department of Microbiology and Immunology of Chicago Medical School at Rosalind Franklin University of Medicine and Science as Associate Professor.

Fabio serves as grant reviewer for the National Institute of Health, the National Science Foundation, and the Welcome Trust. He is Associate Editor for The Journal of Immunology and reviewer for several immunological journals.

RESEARCH INTERESTS

The long-term goal of our lab is to augment our understanding of the role of Toll-like receptors (TLR) and Nod-like receptors (NLR) during innate and adaptive immune responses.

TLR and NLR recognize microbial products and endogenous “danger signals” and activate signaling pathways that initiate the inflammatory response and regulate development of adaptive immunity. Some NLR molecules are part of a multiprotein complex called inflammasome that is responsible for the proteolytic processing and secretion of IL-1b and IL-18.

Our lab investigates the activation of TLR and NLR in distinct experimental settings:

Vaccine adjuvants

Most vaccine adjuvants stimulate the immune system by activating various innate immune receptors. We have found that the vaccine adjuvant Alum activates the NLRP3-inflammasome and we are investigating other pathways that contribute to alum’s adjuvanticity. Understanding at the molecular level the mechanism of action of alum and other adjuvants is a prerequisite for improvement of their immunostimulatory spectrum.

Host-pathogen Interaction

We are interested in defining the role of TLR and NLR during infections with the NAID Select Agents Francisella tularensis and Burkholderia pseudomallei. We are also investigating how the interaction of the intestinal microbiota with the host innate immune system shapes the response to infections and the development of immunity.

Cancer-related Inflammation

Tumorigenesis triggers an inflammatory response and, conversely, inflammation promotes malignant transformation. We are investigating how cancer-related inflammation is initiated and sustained with particular attention to the role of the inflammasome in cancer.

PUBLICATIONS

Selected peer-reviewed publications (out of 41 total publication). (Scopus Citations current as of 2 July 2011)

·  Colotta, F., Re, F., Polentarutti, N., Sozzani, S., and Mantovani, A. (1992).  Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 80:2012-2020 (649)

·  Re, F., Mengozzi, M., Muzio, M., Dinarello, C. A., Mantovani, A., and Colotta, F. (1993).  Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells. Eur. J. Immunol. 23:570-573 (45)

·  Sims, J. E., Gayle, M. A., Slack, J. L., Alderson, M. R., Bird, T. A., Giri, J. G., Colotta, F., Re, F., Mantovani, A., Shanebeck, K., Grabstein, K. H., and Dower, S. K. (1993). Interleukin-1 signaling occurs exclusively via the type I receptor.  Proc. Natl. Acad. Sci. USA 90:6155-6159 (382)

·  Colotta, F., Re, F., Muzio, M., Bertini, R., Polentarutti, N., Sironi, M., Giri, J.  G., Dower, S. K., Sims, J. E., and Mantovani, A. (1993). Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4.  Science 261: 472-475 (548)

·  Colotta, F., Re, F., and Mantovani, A. (1993).  Granulocyte transfusion from G-CSF treated donors: also a question of cell survival?  Blood 85: 2258 (10)

· Re, F., Muzio, M., DeRossi, M., Mantovani, A., and Colotta, F. (1993). The type II 'receptor' as a decoy target for Interleukin-1 in polymorphonuclear leukocytes: characterization of induction by dexamethasone and binding properties of the released decoy receptor.  J. Exp. Med. 179;739-743 (124)

·  Muzio, M., Re, F., Sironi, M., Polentarutti, N., Minty, A., Caput, D., Ferrara, P., Mantovani, A., and Colotta, F. (1994). Interleukin-13 induces the production of Interleukin-1 receptor antagonist (IL-1ra) and expression of the mRNA for the intracellular (keratinocyte) form of IL-1ra in human myelomonocytic cells. Blood 83; 1738-43 (72)

·  Colotta, F., Re, F., Muzio, M., Polentarutti, N., Minty, A., Caput, D., Ferrara, P., and Mantovani, A. (1994).  Interleukin-13 induces expression and release of Interleukin-1 decoy receptor in human polymorphonuclear cells.  J. Biol. Chem. 269;12403-12406 (73)

·  Re, F., Zanetti, A., Sironi, M., Polentarutti, N., Lanfrancone, L., Dejana, E., and Colotta, F. (1994). Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells. J. Cell Biol. 127; 537-546 (338)

·  Re, F., Braaten, D., Franke, E.K., and Luban, J. (1995). Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-Cyclin B. J. Virol. 69, 6859-6864 (265)

·  Re, F., Sironi, M., Muzio, M., Matteucci, C., Introna, M., Orlando, S., Pentol-Rol, G., Dower, S.K., Sims, J., Colotta, F., and Mantovani, A. (1996). Inhibition of Interleukin-1 responsiveness by type II receptor gene transfer: a surface receptor with anti-Interleukin 1 function. J. Exp. Med.183; 1841-1850 (57)

·  Re, F. and Luban, J. (1997) HIV-1 Vpr: G2 cell cycle arrest, macrophages, and nuclear transport. Progress in cell cycle research (Meijer, M., Guidet, S., and Philippe, M., edr.) Vol. 3, 21-27 Plenum Publishing Corporation, New York, NY, USA

·  Re, F. and Strominger, J. L. (2001) Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J. Biol. Chem. 276; 37692-37699 (348)

·  Re, F., Belyanskaya, S., Riese, R. J., Cipriani, B., Fisher, F. R., Granucci, F., Ricciardi-Castagnoli, P., Brosnan, C., Stern, L. J., Strominger, J. L., and Santambrogio, L. (2002) GM-CSF induces an expression program in neonatal microglia that primes them for antigen presentation. J. Immunol. 169; 2264-2273 (49)

·  Re, F. and Strominger, J. L. (2002) Monomeric recombinant MD-2 binds Toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness. J. Biol. Chem. 277; 23427-23432 (71)

·  Sandor, F., Latz, E., Re, F., Mandell, L., Repik, G., Golenbock, D. T., Espevik, T., Kurt-Jones, E. A., and Finberg, R. W. (2003) Importance of extra- and intracellular domains of TLR1 and TLR2 in NF-kB signaling. J. Cell Biol. 162: 1099-1110 (69)

·  Re, F., and Strominger, J. L. (2003) Separate functional domains of human MD-2 mediate TLR4-binding and LPS-responsiveness. J. Immunol. 171:5272-5276 (67)

·  Chang, F*., Re, F.*, and Luban, J. (2004) HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes. Mol. Biol. Cell 15:1793-1801 *equal contribution (22)

·  Re, F., and Strominger, J. L. (2004) Heterogeneity of TLR-induced responses in dendritic cells: from innate to adaptive immunity. Immunobiol. 209:191-198 (26)

·  Finberg, R. W., Re, F., Popova, L., Golenbock, D. T., and Kurt-Jones, E. A. (2004) Cell activation by Toll-like receptors: role of LBP and CD14. J. Endotoxin Res. 10: 413-418 (17)

·  Re, F., and Strominger, J. L. (2004) IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells. J. Immunol. 173:7548-7555 (110)

·  Li, H, Nookala, S., Bina, X. W., Bina, J. E., and Re, F. (2006) Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation. J. Leuk. Biol. 80: 766-773 (32)

·  Prohinar, P., Re, F., Widstrom, R., Zhang, D., Teghanemt, A., Weiss, J. P., and Gioannini, T. L. (2006) Specific high affinity interactions of monomeric endotoxin: protein complexes with Toll-like receptor 4 ectodomain. J. Biol. Chem. 282:1010-1017 (34)

·  Cao, F., Castrillo, A., Tontonoz, P., Re, F., Byrne, G.I. (2006) Chlamydia pneumoniae-induced Macrophage Foam Cell Formation Is Mediated by Toll-Like Receptor 2. Infect Immun. 75:753-759 (52)

·  Li, H., Nookala, S., and Re, F. (2007) Alum Adjuvants Activate Caspase-1 And Induce IL-1b And IL-18 Release. J. Immunol. 178:5271-5276. (68)·  Teghanemt, A., Re, F., Prohinar, P., Widstrom, R., Gioannini, T. L., and Weiss, J. P. (2007). Novel roles in human MD-2 of phenylalanine 121 and 126 and tyrosine 131 in activation of Toll-like Receptor 4 by endotoxin. J. Biol. Chem. 283:1257-1266 (17)

·  Li, H., Nooh, M.M., Kotb, M., and Re, F. (2008) Commercial peptidoglycan preparations are contaminated with superantigen-like activity that stimulates IL-17 production. J. Leuk. Biol. 83:409-418 (15)

·  Thakran, S., Li, H., Lavine, C.L., Miller, M. A., Bina, J. E., Bina, X. R., Re, F. (2008) Identification of Francisella tularensis lipoproteins that stimulate the Toll-like receptor (TLR) 2/TLR1 heterodimer. J. Biol. Chem. 283:3751-3760 (23)

·  Nance, S.C., Yi, A.K., Re, F., Fitzpatrick, E.A.(2008) MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis. J. Leukoc. Biol. 83:1207-17 (4)

·  Li, H., Willingham, S. B., Ting, J. P.-Y., and Re, F. (2008) Cutting Edge: Inflammasome activation by Alum and Alum’s adjuvant effect are mediated by NLRP3. J. Immunol. 181:17-21 (130)

·  Li, H., Ambade, A., and Re, F. (2009) Cutting Edge: Necrosis activates the NLRP3 inflammasome. J. Immunol. 183:1528-1532 (22)

·  Re, F. (2010) Inflammasome activation by pathogenic crystals and particles. Prog. Inflamm. Res. (Martinon, F., Couillin, I., Petrilli, V., eds) (in press)

·  Tsukahara, T., Tsukahara, R., Fujiwara, Y., Yue, J., Cheng, Y., Guo, H., Bolen, A., Zhang, C., Balazs, L., Re, F., Du, G., Frohman, M. A., Baker, D. L., Parrill, A. L., Uchiyama, A., Kobayashi, T., Murakami-Murofushi, K., and Tigyi, G. (2010) Phospholipase D2-dependent Inhibition of the Nuclear Hormone Receptor PPARγ by Cyclic Phosphatidic Acid. Molec. Cell 39:421-432 (5)

·  Jayakar, H., Parvathreddy, J., Fitzpatrick, E. A., Bina, X. R., Bina, J. E., Re, F., Emery, F. D., and Miller, M.A. (2011) A galU mutant of Francisella tularensis is attenuated for virulence in a murine pulmonary model of tularemia. BMC Microbiol. 11:179

·  Madan Lala, R., Peixoto K.V., Re, F., Rengarajan J. (2011) Mycobacterium tuberculosis Hip1 dampens macrophage pro-inflammatory responses by limiting TLR2 activation. Infect. Immun. 79:4828-4838

· Sahoo, M., Ceballos-Olvera, I., Barrio, L. and Re, F. (2011) Role of the inflammasome, IL-1b, and IL-18 in bacterial infections. ScientificWorldJournal 11:2037-2050

· Ceballos-Olvera, I., Sahoo, M., Miller, M. A., Barrio, L., and Re, F. (2011) Inflammasome-dependent Pyroptosis and IL-18 Protect Against Burkholderia   pseudomallei Lung Infection While IL-1b Is Deleterious. PLoS Pathog 7(12): e1002452. doi:10.1371/journal.ppat.1002452

 

 

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