Dr Marc Pellegrini
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Division: Infection and Immunity
Research Overview
Chronic viruses like HIV, Hepatitis C and B and bacteria like Mycobacterium tuberculosis represent an enormous global health threat. Our immune system, which is successful in eliminating a huge array of pathogens, fails to eradicate these persistent organisms. Understanding the mechanisms that circumvent immune responses in cases of massive viral proliferation underlies any rational attempt to augment immunity in HIV infection. We utilize several mouse models that parallel these human diseases. Lymphocytic choriomeningitis virus (LCMV) clone 13 and LCMV docile infection in mice mimic HIV in that they proliferate to very high levels and they disarm the immune response. LCMV clone 13 infection has served as a powerful tool in characterizing the dysfunctional immune response associated with chronic viraemia and this model allows us to study the interplay between host immunity and pathogen at a molecular level.
Research Projects
Which host genes abrogate immunity to chronic infections?
Challenge the paradigm of T cell memory and dissect its failure in preventing disease
Design therapeutics to transiently manipulate host genes to facilitate viral clearance
Major Publications
- Calzascia T*, Pellegrini M*, Lin A, Garza KM, Elford AR, Shahinian A, Ohashi PS,Mak TW. CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2999-3004. Epub 2008 Feb 14. PubMed PMID: 18287017; PubMed Central PMCID: PMC2268574 *Equal contribution
- Calzascia T, Pellegrini M, Hall H, Sabbagh L, Ono N, Elford AR, Mak TW, Ohashi PS.
TNF-alpha is critical for antitumor but not antiviral T cell immunity inmice.
J Clin Invest. 2007 Dec;117(12):3833-45. PubMed PMID: 17992258; PubMed Central PMCID: PMC2066188. - You H, Pellegrini M, Tsuchihara K, Yamamoto K, Hacker G, Erlacher M, Villunger A, Mak TW.
FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal.
J Exp Med. 2006 Jul 10;203(7):1657-63. Epub 2006 Jun 26. PubMed PMID: 16801400; PubMed Central PMCID: PMC2118330. - Pellegrini M, Bath S, Marsden VS, Huang DC, Metcalf D, Harris AW, Strasser A.
FADD and caspase-8 are required for cytokine-induced proliferation of hemopoieticprogenitor cells.
Blood. 2005 Sep 1;106(5):1581-9. Epub 2005 May 19. PubMed PMID:15905188; PubMed Central PMCID: PMC1895211. - Pellegrini M, Bouillet P, Robati M, Belz GT, Davey GM, Strasser A.
Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice.
J Exp Med. 2004 Nov 1;200(9):1189-95. Epub 2004 Oct 25. PubMed PMID:15504823; PubMed Central PMCID: PMC2211860. - Pellegrini M, Belz G, Bouillet P, Strasser A.
Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim.
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14175-80. Epub 2003 Nov 17. PubMed PMID: 14623954; PubMed Central PMCID: PMC283565.
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Current Laboratory Members
Faculty Member: Marc Pellegrini, MB BS BSc PhD Melb FRACP
Research Assistant: Simon Preston, BBiomedSci (Hons) Monash
Research Assistant: Jesse Toe, BSc Melb