Francavilla_group @Manchester

About us

Group interests

We aim at uncovering the molecular mechanisms underlying signaling specificity and cellular outputs during breast cancer progression and metastasis. We focus on:

*exploring how the trafficking of receptor tyrosine kinases (RTKs) from and to the plasma membrane can elicit specific cellular responses, such as cell migration and invasion;

*characterizing the signaling networks underlying breast cancer metastasis in organoids and patient-derived samples.

We use a “functional proteomics” approach, which integrates quantitative mass-spectrometry-based (phospho) proteomics, bioinformatics analysis, functional assays, and advanced imaging techniques (see picture).

The final goal is to identify and characterize proteins with key roles in cellular signaling that can be targeted for personalized intervention in breast cancer patients.

“Functional Proteomics” workflow.

Group Publications

Pedersen A.K., Pfeiffer A., Karemore G., Akimov V., Bekker-Jensen D.B., Blagoev B., Francavilla C.*#, Olsen J.V.#. #, equal senior contribution Proteomic investigation of Cbl and Cbl-b in neuroblastoma cell differentiation highlights roles for SHP-2 and CDK16.(2021).iScience..Mar 17;24(4):102321. doi: 10.1016/j.isci.2021.102321. eCollection 2021 Apr 23. PMID: 33889818.
Parsons J., Francavilla C.*'Omics Approaches to Explore the Breast Cancer Landscape.(2020).Front Cell Dev Biol..Jan 22;7:395. doi: 10.3389/fcell.2019.00395. eCollection 2019. Review.
Pearson A. J., Fullwood P., Toro Tapia G., Prise I., Smith M.P., Xu Q., Jordan A., Giurisato E., Whitmarsh A.J., Francavilla C., Tournier C..Discovery of a Gatekeeper Residue in the C-Terminal Tail of the Extracellular Signal-Regulated Protein Kinase 5 (ERK5).(2020).Int J Mol Sci. .Jan 31;21(3). pii: E929. doi: 10.3390/ijms21030929.
Hamilton W. B., Mosesson Y., Monteiro R.S., Emdal K. B., Knudsen T.E., Francavilla C., Barkai N., Olsen J.V., Brickman J.M..Dynamic lineage priming is driven via direct enhancer regulation by ERK.(2019).Nature.Nov;575(7782):355-360. doi: 10.1038/s41586-019-1732-z. Epub 2019 Nov 6.
Lundby A., Franciosa G., Emdal K.B., Refsgaard J.C., Gnosa S. P., Bekker-Jensen D.B., Secher A., Maurya S. R., Paul I., Mendez B.I., Kelstrup C.D., Francavilla C., Kveilborg M., Montoya G., Jensen L.J., Olsen J.V..Oncogenic mutations rewire signaling pathways by switching protein recruitment to phosphotyrosine sites .(2019).Cell.Oct 3;179(2):543-560.e26. doi: 10.1016/j.cell.2019.09.008.
Zamai M., Trullo A., Giordano M., Corti V., Cuesta E. A., Francavilla C., Cavallaro U., Caiolfa V. R..Number and brightness analysis in live cells reveals that NCAM and FGF2 elicit different assembly and dynamics of FGFR1.(2019).J Cell Sci .Jan 3;132(1). pii: jcs220624. doi: 10.1242/jcs.220624.
Emdal K. B., Pedersen A. K., Bekker-Jensen D. B., Lundby A., Claeys S., De Preter K., Speleman F., Francavilla C.*#, Olsen J. V.*#. #, equal senior contributionIntegrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma.(2018).Sci Signal.Nov 20;11(557).
Watson J., Francavilla C.*Regulation of FGF10 Signaling in Development and Disease.(2018).Front Genet.Oct 23;9:500.
Batth T.S., Papetti M., Pfeiffer A., Tollenaere M.A.X., Francavilla C.*, and Olsen J.V.*.Large-scale phosphoproteomics reveals Shp2 phosphatase-dependent regulators of Pdgf receptor signaling.(2018).Cell Rep.Mar 6;22(10):2784-2796.
Sanchez-Quiles V., Akimov V., Osinalde N., Francavilla C., Puglia M., Barrio-Hernandez I., Kratchmarova I., Olsen J.V., Blagoev B..Cylindromatosis Tumor Suppressor Protein (CYLD) Deubiquitinase is Necessary for Proper Ubiquitination and Degradation of the Epidermal Growth Factor Receptor.(2017).Mol Cell Proteomics. Aug;16(8):1433-1446.
Francavilla C.*, Lupia M., Tsafou K., Villa A., Kowalczyk K., Rakownikow Jersie-Christensen R., Bertalot G., Confalonieri S., Brunak S., Jensen L.J., Cavallaro U.*, Olsen J.V.*.Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer.(2017).Cell Rep. Mar 28;18(13):3242-3256.
Francavilla C.*, Papetti M., Rigbolt T.G., Pedersen A-K., Sirurdson J.O., Cazzamali G., Karemore G., Blagoev B., Olsen J.V.*.Multi-layered Proteomics reveals Molecular Switches Dictating Ligand-dependent EGFR Trafficking.(2016).Nat. Struct. Mol. Biol. 23(6):608-18.
Von Stechow L., Francavilla C., Olsen J.V.Recent findings and technological advances in phopshoproteomics for cells and tissues.(2015).Expert. Rev. Proteomics.12(5): 469-487.
Satpathy S., Wagner S.A., Beli P., Gupta R., Kristiansen T.A., Malinova D., Francavilla C., Tolar P., Bishop G.A., Hostager B.S., Choudhary C Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation.(2015).Molecular systems biology.11(6): 810 (Highlighted in the Editors' Choice section of Science Signaling: B cell receptor signaling dynamics, Sudhakaran Prabakaran, (2015) Sci Signal. 8, Issue 384, pp. ec186).
Emdal K.B., Pedersen A.K., Bekker-Jensen D.B., Tsafou K.P., Horn H., Lindner S., Schulte J.H., Eggert A., Jensen L.J., Francavilla C.*#, Olsen J.V.*#.#, equal senior contributionTemporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation.(2015).Science signaling. 8(374): ra40 (Featured with the cover image).
Batth T.S., Francavilla C., Olsen J.VOff-line high-pH reversed-phase fractionation for in-depth phosphoproteomics.(2014).Journal of proteome research.Dec 5, 13(12): 6176-86.
Francavilla C., Hekmat O., Blagoev B., Olsen J.VSILAC-based temporal phosphoproteomics.(2014).Methods Mol Biol.Jul, 1188: 125-48.
Schimmel J., Eifler K., Sigurethsson J.O., Cuijpers S.A., Hendriks I.A., Verlaan-de Vries M., Kelstrup C.D., Francavilla C., Medema R.H., Olsen J.V., Vertegaal A.C.Uncovering SUMOylation dynamics during cell-cycle progression reveals FoxM1 as a key mitotic SUMO target protein.(2014).Molecular cell..Mar 20, 53(6): 1053-66.
Petersen D.L., Krejsgaard T., Berthelsen J., Fredholm S., Willerslev-Olsen A., Sibbesen N.A., Bonefeld C.M., Andersen M.H., Francavilla C., Olsen J.V., Hu T., Zhang M., Wasik M.A., Geisler C., Woetmann A., Odum N. B-lymphoid tyrosine kinase (Blk) is an oncogene and a potential target for therapy with dasatinib in cutaneous T-cell lymphoma (CTCL).(2014).Leukemia.Oct, 28(10): 2109-12.
Radhakrishnan P., Dabelsteen S., Madsen F.B., Francavilla C., Kopp K.L., Steentoft C., Vakhrushev S.Y., Olsen J.V., Hansen L., Bennett E.P., Woetmann A., Yin G., Chen L., Song H., Bak M., Hlady R.A., Peters S.L., Opavsky R., Thode C., Qvortrup K., Schjoldager K.T., Clausen H., Hollingsworth M.A., Wandall H.H. Immature truncated O-glycophenotype of cancer directly induces oncogenic features.(2014).Proceedings of the National Academy of Sciences of the United States of America.Sep 30, 111(39): E4066-75.
Lundby A., Andersen M.N., Steffensen A.B., Horn H., Kelstrup C.D., Francavilla C., Jensen L.J., Schmitt N., Thomsen M.B., Olsen J.V. In vivo phosphoproteomics analysis reveals the cardiac targets of beta-adrenergic receptor signaling.(2013).Science signaling.Jun 4, 6(278): rs11.
Galli G.G., Carrara M., Francavilla C., de Lichtenberg K.H., Olsen J.V., Calogero R.A., Lund A.H. Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells.(2013).Molecular and cellular biology.Nov, 33(22): 4504-16.
Hekmat O., Munk S., Fogh L., Yadav R., Francavilla C., Horn H., Wurtz S.O., Schrohl A.S., Damsgaard B., Romer M.U., Belling K.C., Jensen N.F., Gromova I., Bekker-Jensen D.B., Moreira J.M., Jensen L.J., Gupta R., Lademann U., Brunner N., Olsen J.V., Stenvang J. TIMP-1 increases expression and phosphorylation of proteins associated with drug resistance in breast cancer cells.(2013).Journal of proteome research.Sep 6, 12(9): 4136-51..
Francavilla C., Rigbolt K.T., Emdal K.B., Carraro G., Vernet E., Bekker-Jensen D.B., Streicher W., Wikstrom M., Sundstrom M., Bellusci S., Cavallaro U., Blagoev B., Olsen J.V.Functional proteomics defines the molecular switch underlying FGF receptor trafficking and cellular outputs..(2013).Molecular cell.Sep 26, 51(6): 707-22 (Highlighted in the Editors' Choice section of Science Signaling: Dictating the Route, Nancy R. Gough, (2013) Sci Signal. 6, Issue 295, pp. ec236).
Kelstrup C.D., Hekmat O., Francavilla C., Olsen J.V. Pinpointing phosphorylation sites: Quantitative filtering and a novel site-specific x-ion fragment.(2011).Journal of proteome research.Jul 1, 10(7): 2937-48.
Murakami M., Francavilla C., Torselli I., Corada M., Maddaluno L., Sica A., Matteoli G., Iliev I.D., Mantovani A., Rescigno M., Cavallaro U., Dejana E. nactivation of junctional adhesion molecule-A enhances antitumoral immune response by promoting dendritic cell and T lymphocyte infiltration.(2010).Cancer research.Mar 1, 70(5): 1759-65.
Monegal A., Ami D., Martinelli C., Huang H., Aliprandi M., Capasso P., Francavilla C., Ossolengo G., de Marco A. Immunological applications of single-domain llama recombinant antibodies isolated from a naive library.(2009).Protein engineering, design & selection : PEDS.Apr, 22(4): 273-80.
Francavilla C., Cattaneo P., Berezin V., Bock E., Ami D., de Marco A., Christofori G., Cavallaro U. The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking.(2009).The Journal of cell biology.Dec 28, 187(7): 1101-16.
Francavilla C.#, Maddaluno L.#, Cavallaro U. #, equal contribution he functional role of cell adhesion molecules in tumor angiogenesis..(2009).Seminars in cancer biology..Oct, 19(5): 298-309.
Francavilla C., Loeffler S., Piccini D., Kren A., Christofori G., Cavallaro U. Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor.(2007).Journal of cell science.Dec 15, 120(Pt 24): 4388-94.
* corresponding author

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Chiara Francavilla

Chiara Francavilla
Chiara got her PhD in Molecular Medicine in Milan in 2009 and, after six years in Copenhagen as a post-doctoral fellow working on "functional proteomics", Chiara started her own group as a Wellcome Trust-funded independent fellow at the University of Manchester in 2016.
biography

Current Group Members

Dr Michael P. Smith
Postdoctoral fellow (PDRA)
Funded by Wellcome Trust
Jennifer Ferguson Haworth
Technician
Funded by BBSRC
Paul Fullwood
Experimental Officer
Funded by The University of Manchester and by Wellcome Trust
Joanne Watson
PhD student 2017-2021
Funded by BBSRC. Co-supervised with Dr Jean-marc Schwartz and Dr Patrick Caswell (The University of Manchester)
Harriet Ferguson
PhD student 2018-2022
Funded by BBSRC. Co-supervised with Prof Andy Sharrocks and Prof Simon Hubbard (The University of Manchester)
Joseph Parsons
PhD student 2018-2022
Funded by Cancer UK. Co-supervised with Dr Robert Clarke (MCRC) and Dr MD Ciara o'Brien (The Christie Hospital)

Co-supervised PhD students

Tom Kedward – Funded by BRC (2017-2021). Co-supervised with Dr Robert Clarke and Dr Sasha Howell (MCRC, Manchester)

 

 

Emily Goodall – Funded by BBSRC (2019-2023). Co-supervised with Dr Pat Caswell and Dr J-m Schwartz (The University of Manchester).

Previous Group Members

C. Bates, Wellcome Trust MCB PhD student (Oct – Dec 2016); B. Hale, UG (Dec 2016 – Mar 2017); R. Yarwood, Wellcome Trust MCB PhD student (Jan – March 2017); J. Bowles, Wellcome Trust QBB PhD student (Oct 2017 – Feb 2018); C. Goncalves, Wellcome Trust MCB PhD student (Jan – March 2018); S. Saleh, UG (Dec 2017 – Apr 2018); Dr K. Kowalczyk, RA (2016-2018); H. Sun, technician (Feb – Oct 2018); S. Chandler, UG (Dec 2018 – Apr 2019); R. Brady, Wellcome Trust MCB PhD student (Apr – July 2019); N. Alachkar, Wellcome Trust QBB PhD student (Apr – July 2019); A. Asante-Sakyi UG (Jan-Mar 2019); A. Hopkins UG (Jan- March 2020); K. Bexley, MSci (Oct 2020 – July 2021)

Visitors

Dr Arndt Rohwedder, University of Leeds (June 2017 – July 2018)

Photowall!

Ben Hale at his graduation
In the Lab (2016)
Chiara @ HuPo, Dublin, Ireland, Sept 2017
Group picture in Spring 2018
2018 C-wing Christmas Party. So much fun!
The team after our first typical Italian lunch @ Salvi's, Manchester in April 2019
Christmas Party 2020: how to have fun during lockdown!