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LUIGI NEZI

MICROBIOME & CANCER

 

The most recent estimate of microbes populating the human body is around 40 trillion. This means that we are made of bacteria at least as much of human cells and that they coexist on our body as result of a dynamic equilibrium between Darwinian competition and cooperation. There is a growing appreciation of the role of the microbiome in cancer-related outcomes and our recent work demonstrated that differential bacterial “signatures” exist in the gut of melanoma patients that responded (R) or not (NR) to immunotherapy. Building on the synergy between scientists from different background, our lab is seeking for innovative strategies to improve cancer prevention and response to immunotherapy by manipulating the human microbiome. We are interested in molecular mechanisms that regulate the crosstalk between innate and adaptive immune system in response to modulation of the microbiome in cancer patients.
We are performing multiOMIC analysis and developing new ex vivo and in vivo systems to create:

  • diagnostic tools, that could by reveal high-risk subjects or potential R and NR patients, and guide subsequent prophylactic treatments or immune-based therapeutic choices;
  • personalized interventions, by combining biotic and abiotic formulations to promote cancer prevention or turn an NR in an R.

 

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
Gopalakrishnan V*, Spencer CN*, Nezi L*, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA.
Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.

PAF promotes stemness and radioresistance of glioma stem cells.
Ong DST, Hu B, Ho YW, Sauvé CG, Bristow CA, Wang Q, Multani AS, Chen P, Nezi L, Jiang S, Gorman CE, Monasterio MM, Koul D, Marchesini M, Colla S, Jin EJ, Sulman EP, Spring DJ, Yung WA, Verhaak RGW, Chin L, Wang YA, DePinho RA.
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E9086-E9095. doi: 10.1073/pnas.1708122114. Epub 2017 Oct 9.

Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma.
Reuben A, Spencer CN, Prieto PA, Gopalakrishnan V, Reddy SM, Miller JP, Mao X, De Macedo MP, Chen J, Song X, Jiang H, Chen PL, Beird HC, Garber HR, Roh W, Wani K, Chen E, Haymaker C, Forget MA, Little LD, Gumbs C, Thornton RL, Hudgens CW, Chen WS, Austin-Breneman J, Sloane RS, Nezi L, Cogdill AP, Bernatchez C, Roszik J, Hwu P, Woodman SE, Chin L, Tawbi H, Davies MA, Gershenwald JE, Amaria RN, Glitza IC, Diab A, Patel SP, Hu J, Lee JE, Grimm EA, Tetzlaff MT, Lazar AJ, Wistuba II, Clise-Dwyer K, Carter BW, Zhang J, Futreal PA, Sharma P, Allison JP, Cooper ZA, Wargo JA.
NPJ Genom Med. 2017;2. pii: 10. doi: 10.1038/s41525-017-0013-8. Epub 2017 Apr 7.

ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma.
Marchesini M, Ogoti Y, Fiorini E, Aktas Samur A, Nezi L, D'Anca M, Storti P, Samur MK, Ganan-Gomez I, Fulciniti MT, Mistry N, Jiang S, Bao N, Marchica V, Neri A, Bueso-Ramos C, Wu CJ, Zhang L, Liang H, Peng X, Giuliani N, Draetta G, Clise-Dwyer K, Kantarjian H, Munshi N, Orlowski R, Garcia-Manero G, DePinho RA, Colla S.
Cancer Cell. 2017 Jul 10;32(1):88-100.e6. doi: 10.1016/j.ccell.2017.05.011. Epub 2017 Jun 29.

Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer.
Genovese G, Carugo A, Tepper J, Robinson FS, Li L, Svelto M, Nezi L, Corti D, Minelli R, Pettazzoni P, Gutschner T, Wu CC, Seth S, Akdemir KC, Leo E, Amin S, Molin MD, Ying H, Kwong LN, Colla S, Takahashi K, Ghosh P, Giuliani V, Muller F, Dey P, Jiang S, Garvey J, Liu CG, Zhang J, Heffernan TP, Toniatti C, Fleming JB, Goggins MG, Wood LD, Sgambato A, Agaimy A, Maitra A, Roberts CW, Wang H, Viale A, DePinho RA, Draetta GF, Chin L.
Nature. 2017 Feb 16;542(7641):362-366. doi: 10.1038/nature21064. Epub 2017 Feb 8.

In Vivo Functional Pla+tform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer.
Carugo A, Genovese G, Seth S, Nezi L, Rose JL, Bossi D, Cicalese A, Shah PK, Viale A, Pettazzoni PF, Akdemir KC, Bristow CA, Robinson FS, Tepper J, Sanchez N, Gupta S, Estecio MR, Giuliani V, Dellino GI, Riva L, Yao W, Di Francesco ME, Green T, D'Alesio C, Corti D, Kang Y, Jones P, Wang H, Fleming JB, Maitra A, Pelicci PG, Chin L, DePinho RA, Lanfrancone L, Heffernan TP, Draetta GF.
Cell Rep. 2016 Jun 28;16(1):133-147. doi: 10.1016/j.celrep.2016.05.063. Epub 2016 Jun 16.

Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.
Lissanu Deribe Y, Shi Y, Rai K, Nezi L, Amin SB, Wu CC, Akdemir KC, Mahdavi M, Peng Q, Chang QE, Hornigold K, Arold ST, Welch HC, Garraway LA, Chin L.
Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1296-305. doi: 10.1073/pnas.1513801113. Epub 2016 Feb 16.

Genomic Classification of Cutaneous Melanoma.
Cancer Genome Atlas Network.
Cell. 2015 Jun 18;161(7):1681-96. doi: 10.1016/j.cell.2015.05.044.

Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome.
Colla S, Ong DS, Ogoti Y, Marchesini M, Mistry NA, Clise-Dwyer K, Ang SA, Storti P, Viale A, Giuliani N, Ruisaard K, Ganan Gomez I, Bristow CA, Estecio M, Weksberg DC, Ho YW, Hu B, Genovese G, Pettazzoni P, Multani AS, Jiang S, Hua S, Ryan MC, Carugo A, Nezi L, Wei Y, Yang H, D'Anca M, Zhang L, Gaddis S, Gong T, Horner JW, Heffernan TP, Jones P, Cooper LJ, Liang H, Kantarjian H, Wang YA, Chin L, Bueso-Ramos C, Garcia-Manero G, DePinho RA.
Cancer Cell. 2015 May 11;27(5):644-57. doi: 10.1016/j.ccell.2015.04.007.

Genetic events that limit the efficacy of MEK and RTK inhibitor therapies in a mouse model of KRAS-driven pancreatic cancer.
Pettazzoni P, Viale A, Shah P, Carugo A, Ying H, Wang H, Genovese G, Seth S, Minelli R, Green T, Huang-Hobbs E, Corti D, Sanchez N, Nezi L, Marchesini M, Kapoor A, Yao W, Francesco ME, Petrocchi A, Deem AK, Scott K, Colla S, Mills GB, Fleming JB, Heffernan TP, Jones P, Toniatti C, DePinho RA, Draetta GF.
Cancer Res. 2015 Mar 15;75(6):1091-101. doi: 10.1158/0008-5472.CAN-14-1854. Epub 2015 Mar 3.

Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function.
Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sánchez N, Marchesini M, Carugo A, Green T, Seth S, Giuliani V, Kost-Alimova M, Muller F, Colla S, Nezi L, Genovese G, Deem AK, Kapoor A, Yao W, Brunetto E, Kang Y, Yuan M, Asara JM, Wang YA, Heffernan TP, Kimmelman AC, Wang H, Fleming JB, Cantley LC, DePinho RA, Draetta GF.
Nature. 2014 Oct 30;514(7524):628-32. doi: 10.1038/nature13611. Epub 2014 Aug 10.

Role of the Mad2 dimerization interface in the spindle assembly checkpoint independent of kinetochores.
Mariani L, Chiroli E, Nezi L, Muller H, Piatti S, Musacchio A, Ciliberto A.
Curr Biol. 2012 Oct 23;22(20):1900-8. doi: 10.1016/j.cub.2012.08.028. Epub 2012 Sep 20.

Passenger deletions generate therapeutic vulnerabilities in cancer.
Muller FL, Colla S, Aquilanti E, Manzo VE, Genovese G, Lee J, Eisenson D, Narurkar R, Deng P, Nezi L, Lee MA, Hu B, Hu J, Sahin E, Ong D, Fletcher-Sananikone E, Ho D, Kwong L, Brennan C, Wang YA, Chin L, DePinho RA.
Nature. 2012 Aug 16;488(7411):337-42. doi: 10.1038/nature11331. Erratum in: Nature. 2015 Sep 10;525(7568):278.

DNA breaks and chromosome pulverization from errors in mitosis.
Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D.
Nature. 2012 Jan 18;482(7383):53-8. doi: 10.1038/nature10802.

Sister chromatid tension and the spindle assembly checkpoint.
Nezi L, Musacchio A.
Curr Opin Cell Biol. 2009 Dec;21(6):785-95. doi: 10.1016/j.ceb.2009.09.007. Epub 2009 Oct 19. Review.

Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration.
Carlucci A, Gedressi C, Lignitto L, Nezi L, Villa-Moruzzi E, Avvedimento EV, Gottesman M, Garbi C, Feliciello A.
J Biol Chem. 2008 Apr 18;283(16):10919-29. doi: 10.1074/jbc.M707248200. Epub 2008 Jan 26.

Accumulation of Mad2-Cdc20 complex during spindle checkpoint activation requires binding of open and closed conformers of Mad2 in Saccharomyces cerevisiae.
Nezi L, Rancati G, De Antoni A, Pasqualato S, Piatti S, Musacchio A.
J Cell Biol. 2006 Jul 3;174(1):39-51.

Determinants of conformational dimerization of Mad2 and its inhibition by p31comet.
Mapelli M, Filipp FV, Rancati G, Massimiliano L, Nezi L, Stier G, Hagan RS, Confalonieri S, Piatti S, Sattler M, Musacchio A.
EMBO J. 2006 Mar 22;25(6):1273-84. Epub 2006 Mar 9.

Extra-mitochondrial localisation of frataxin and its association with IscU1 during enterocyte-like differentiation of the human colon adenocarcinoma cell line Caco-2.
Acquaviva F, De Biase I, Nezi L, Ruggiero G, Tatangelo F, Pisano C, Monticelli A, Garbi C, Acquaviva AM, Cocozza S.
J Cell Sci. 2005 Sep 1;118(Pt 17):3917-24. Epub 2005 Aug 9.

The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint.
De Antoni A, Pearson CG, Cimini D, Canman JC, Sala V, Nezi L, Mapelli M, Sironi L, Faretta M, Salmon ED, Musacchio A.
Curr Biol. 2005 Feb 8;15(3):214-25.

Characterization of DIP1, a novel nuclear protein in Drosophila melanogaster.
De Felice B, Wilson RR, Mondola P, Matrone G, Damiano S, Garbi C, Nezi L, Su TT.
Biochem Biophys Res Commun. 2003 Jul 25;307(2):224-8.

The role of proteases in fibronectin matrix remodeling in thyroid epithelial cell monolayer cultures.
Nezi L, Greco D, Nitsch L, Garbi C.
Biol Chem. 2002 Jan;383(1):167-76.