I am interested in how the body initiates an innate immune response to infectious pathogens and then maintains ‘helpful’, rather than ‘damaging’ inflammatory responses.

The SOCS proteins are classic negative regulators that act as a handbrake to limit the damage associated with excessive pro-inflammatory cytokine signalling. TRIM proteins are another important class of intracellular proteins which both positively and negatively regulate innate immune signalling.

Our research program aims to understand the molecular detail of SOCS and TRIM protein complexes and how these signalling complexes are regulated in inflammatory and infectious disease. We are taking an integrated multi-disciplinary approach, which utilises in vivo model systems, quantitative proteomics and structural biology.

Ultimately, I am interested in the connection between the deregulation of intracellular signalling and disease. Within this context, my research is focused on understanding how these protein families regulate innate immunity.


Selected publications from Prof Sandra Nicholson

Kedzierski L, Tate M, Hsu A C-Y, Kolesnik TB, Dagley L, Dong Z, Linossi E, Freeman S, Infusini G, Bird N, Chatfield SM, Belz, G, Webb A, Wark PAB, Nicola NA, Xu J, Kedzierska K, Hansbro PM, Nicholson SE. Suppressor of Cytokine Signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR-PI3K signaling. 2017 eLIFE doi:10.7554/eLife.20444 PMID: 28195529

Delconte RB, Kolesnik TB, Dagley LF, Rautela J, Shi W, Putz EM, Stannard K, Zhang J-G, The C, Firth M, Ushiki T, Andoniou CE, Degli-Esposti MA, Sharp PP, Sanvitale CE, Infusini G, Liau NPD, Linossi EM, Burns CJ, Carotta S, Gray DHD, Seillet C, Hutchinson DS, Belz GT, Webb AI, Alexander WS, Li SS, Bullock AN, Babon JJ, Smyth MJ, Nicholson SE, Huntington ND. CIS is a potent checkpoint in NK cell-mediated tumour immunity. Joint senior author, Nature Immunology 2016 17, 816–824 PMID: 27213690

Kedzierski L, Linossi EM, Kolesnik TB, Day EB, Bird NL, Kile BT, Belz GT, Metcalf D, Nicola NA, Kedzierska K, Nicholson SE. Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection. PLoS Pathog. 2014 May;10(5):e1004134. PMID: 24809749.

D’Cruz AA, Kershaw NJ, Chiang JJ, Wang MK, Nicola NA, Babon JJ, Gack MU, Nicholson SE. Crystal structure of the TRIM25 B30.2 (PRYSPRY) domain: a key component of antiviral signalling. Biochem J. 2013 Dec 1;456(2):231-40. PMID: 24015671.

Lewis RS, Kolesnik TB, Kuang Z, D’Cruz AA, Blewitt ME, Masters SL, Low A, Willson T, Norton RS, Nicholson SE. TLR regulation of SPSB1 controls inducible nitric oxide synthase induction. J Immunol. 2011 Oct 1;187(7):3798-805. PMID: 21876038.

Kuang Z, Lewis RS, Curtis JM, Zhan Y, Saunders BM, Babon JJ, Kolesnik TB, Low A, Masters SL, Willson TA, Kedzierski L, Yao S, Handman E, Norton RS, Nicholson SE. The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation. J Cell Biol. 2010 Jul 12;190(1):129-41. PMID: 20603330.

Masters SL, Yao S, Willson TA, Zhang JG, Palmer KR, Smith BJ, Babon JJ, Nicola NA, Norton RS, Nicholson SE. The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues. Nat Struct Mol Biol. 2006 Jan;13(1):77-84. PMID: 16369487.

Babon JJ, McManus EJ, Yao S, DeSouza DP, Mielke LA, Sprigg NS, Willson TA, Hilton DJ, Nicola NA, Baca M, Nicholson SE, Norton RS. The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability. Mol Cell. 2006 Apr 21;22(2):205-16. PMID: 16630890.

Nicholson SE, De Souza D, Fabri LJ, Corbin J, Willson TA, Zhang JG, Silva A, Asimakis M, Farley A, Nash AD, Metcalf D, Hilton DJ, Nicola NA, Baca M. Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6493-8. PMID: 10829066.

Nicholson SE, Willson TA, Farley A, Starr R, Zhang JG, Baca M, Alexander WS, Metcalf D, Hilton DJ, Nicola NA. Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J. 1999 Jan 15;18(2):375-85. PMID: 9889194.

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