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Background

The Gissen group use cell and molecular biology approaches to investigate rare genetic disorders affecting intracellular trafficking and metabolism. The development of novel therapies to treat these disorders is the focus for the group.

Our long-standing interest is in understanding the mechanism of function of a multi-protein tethering complex containing VPS33B and VIPAR. Defects in these two proteins cause a range of human disorders affecting different tissues including liver, kidneys, bones and blood cells. For this work and other studies we employ cell and animal models of human disease.Ìý

The close proximity to Great Ormond Street Hospital (GOSH) gives us a unique opportunity to take a leading role in the clinical trials of novel therapies in inherited metabolic disorders working closely with the GOSH R&I department, Clinical IMD department and various industry and academic sponsors. Thus, translation of laboratory research into clinical practice is key for us!

Projects and key publications

1. ARC syndrome pathobiology and treatment development

Key collaborators: David Long, Adrian Thrasher, Claire Booth

Gruber R, Rogerson C, Windpassinger C, Banushi B, Straatman-Iwanowska A, Hanley J, Forneris F, Strohal R, Ulz P, Crumrine D, Menon GK, Blunder S, Schmuth M, Müller T,ÌýSmith H, Mills K, Kroisel P, Janecke AR,ÌýGissen P.J Invest Dermatol. 2017 Apr;137(4):845-854.

Hanley J, Dhar DK, Mazzacuva F, Fiadeiro R, Burden JJ, Lyne AM,ÌýSmith H, Straatman-Iwanowska A, Banushi B, Virasami A, Mills K, Lemaigre FP, Knisely AS, Howe S, Sebire N, Waddington SN, Paulusma CC, Clayton P,ÌýGissen P. J Hepatol. 2017 May;66(5):1001-1011.

Banushi B, Forneris F, Straatman-Iwanowska A, Strange A, Lyne AM, Rogerson C, Burden JJ, Heywood WE, Hanley J, Doykov I, Straatman KR, Smith H,ÌýBem D, Kriston-Vizi J, Ariceta G, Risteli M, Wang C, Ardill RE, Zaniew M, Latka-Grot J, Waddington SN, Howe SJ, Ferraro F, Gjinovci A, Lawrence S, Marsh M, Girolami M, Bozec L, Mills K,ÌýGissen P.Nat Commun. 2016 Jul 20;7:12111.

Bem D, Smith H, Banushi B, Burden JJ, White IJ, Hanley J, Jeremiah N, Rieux-Laucat F, Bettels R, Ariceta G, Mumford AD, Thomas SG, Watson SP,ÌýGissen P. Blood. 2015 Jul 9;126(2):133-43.

Cullinane AR, Straatman-Iwanowska A, Zaucker A, Wakabayashi Y, Bruce CK, Luo G, Rahman F, Gürakan F, Utine E, Ozkan TB, Denecke J, Vukovic J, Di Rocco M, Mandel H, Cangul H, Matthews RP, Thomas SG, Rappoport JZ, Arias IM, Wolburg H, Knisely AS, Kelly DA, Müller F, Maher ER,ÌýGissen P. Nat Genet. 2010 Apr;42(4):303-12.

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2. Development of therapies for metabolic liver disorders

Key collaborators: Ian Alexander (University of Sydney, Australia), Simon Waddington, Julien Baruteau, Philippa Mills, John Counsell, Haiyan Zhou

Baruteau J, Cunningham SC, Yilmaz BS, Perocheau DP, Eaglestone S, Burke D, Thrasher AJ, Waddington SN, Lisowski L, Alexander IE,ÌýGissen P. Mol Ther Methods Clin Dev. 2021 Sep 14;23:135-146.

Lorvellec M, Pellegata AF, Maestri A, Turchetta C, Alvarez Mediavilla E, Shibuya S, Jones B, Scottoni F, Perocheau DP, Cozmescu AC, Delhove JM, Kysh D, Gjinovci A, Counsell JR, Heywood WE, Mills K, McKay TR, De Coppi P,ÌýGissen P.iScience. 2020 Nov 13;23(12):101808.

Lorvellec M, Scottoni F, Crowley C, Fiadeiro R, Maghsoudlou P, Pellegata AF, Mazzacuva F, Gjinovci A, Lyne AM, Zulini J, Little D, Mosaku O, Kelly D, De Coppi P,ÌýGissen P.PLoS One. 2017 Dec 20;12(12):e0189586.

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3. Biomarkers of metabolic diseases

Key collaborators: Philippa Mills, Kevin Mills, Peter Clayton, Wendy Heywood

Papandreou A, Doykov I, Spiewak J, Komarov N, Habermann S, Kurian MA, Mills PB, Mills K,ÌýGissen P,ÌýHeywood WE; Clinical cohort recruitment and characterization group.Dev Med Child Neurol. 2022 Jul 14.

Iwan K, Patel N, Heslegrave A, Borisova M, Lee L, Bower R, Mole SE, Mills PB, Zetterberg H, Mills K,ÌýGissen P,ÌýHeywood WE.F1000Res. 2021 Jul 20;10:614.

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4. Clinical trials for metabolic disorders

Schulz A, Ajayi T, Specchio N, de Los Reyes E,ÌýGissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschütter A; CLN2 Study Group.N Engl J Med. 2018 May 17;378(20):1898-1907.

Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, Armant M, Dansereau C, Lund TC, Miller WP, Raymond GV, Sankar R, Shah AJ, Sevin C, Gaspar HB,ÌýGissen P, Amartino H, Bratkovic D, Smith NJC, Paker AM, Shamir E, O'Meara T, Davidson D, Aubourg P, Williams DA. N Engl J Med. 2017 Oct 26;377(17):1630-1638.

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Funders

Great Ormond Street Hospital Charity

Wellcome Trust

MRC

NIHR

Batten Disease Family Association

ERC

BioMarin