Dr Giovanna Nalesso
About
Biography
I have a degree in Pharmaceutical Biotechnology acquired at the University of Padova (Italy) in 2006. I moved to the UK in the same year to work for Glaxo Smith Kline until September 2007 when I then started my PhD at Queen Mary University of London, which was focussed on the characterization of the Wnt signalling pathway in the articular cartilage and osteoarthritis. I joined the University of Surrey in 2017 as lecturer in Musculoskeletal Biology at the School of Veterinary Medicine.
University roles and responsibilities
- Research Director of the School of Veterinary Medicine
Previous roles
ResearchResearch interests
I lead a research group focussed in understanding the molecular mechanisms associated with the pathogenesis of osteoarthritis (OA). OA is a musculoskeletal condition characterised by degeneration of the articular cartilage and abnormal bone remodelling. Despite being a high disabling disease, only symptomatic treatment is currently available to patients until surgical joint replacement is required. The lack of non-invasive therapeutic treatments is linked to the poor understanding of OA pathogenesis and consequently to the lack pro-regenerative pharmacological targets.
Our goal is to better understand OA pathogenesis to drive the development of new drugs to treat OA.
To this end we are working on four different areas:
1) We aim to characterise the role of microRNAs in the modulation of the Wnt signalling in the articular cartilage. The Wnt signalling plays a pivotal role in regenerative processes and it is de-regulated in OA (Nalesso et al, JCB 2011; Nalesso et al., Annals of Rheumatic Diseases 2017). We want to identify the molecular drivers regulating its homeostasis in physiological conditions to re-establish their function in disease. This work is in collaboration with the McCormick's group at Queen Mary University of London and has been funded through a New Investigator Research Grant awarded by the MRC in 2019.
2) We are investigating the role of Calcium Calmodulin Kinase II (CaMKII) in the modulation of lipid metabolism in OA. We have shown that CaMKII inhibition exacerbate OA progression in animal models of OA and this was associated with metabolic changes in the articular cartilage (Nalesso et al., JCB 2011; Nalesso et al. Sci Rep 2021). We aim to define new therapeutic targets by characterising the link between altered cell metabolism and tissue degeneration. Two PhD studentships have been funded under this research topic through funds awarded by the Academy of Medical Sciences Springboard Award, the Longhurst Legacy Fund and the UoS Doctoral College. The projects are in partnership with Dr Fielding at the School of Biosciences (UoS) and Prof Campanella at the RVC.
3) We want to determine key age-associated changes in the extracellular matrix of the articular cartilage to develop new ex-vivo models to study how aging affects signalling in the tissue and modify the response to drugs. This will help in reducing the use of animals in pre-clinical studies and will inform the development of more effective drugs for aged patients, who are the mostly affected by OA. This project is one of five studentships awarded by the Dunhill Medical Trust as part of the Engineering novel in-vitro Model systems to accelERate aGEing research doctoral training programme (EMERGE DTP).
4) We want to investigate whether environmental conditions and exposure to pollutants can affect cartilage health and the development of OA. This will lead to preventative measures aimed to reduce the number of people affected by OA and/or to slow down disease progression. This work is in collaboration with Prof FArsky's laboratory at the University of Sao Paulo.
Research collaborations
Dr Kamalan Jeevaratnam, Prof Barbara Fielding, Dr Paola Campagnolo, University of Surrey
Mrs Kathryn Gill, Royal Surrey County Hospital
Dr Peter McCormick and Prof Francesco dell’Accio, Queen Mary University of London
Prof Michelangelo Campanella, Royal Veterinary College
Profs Graham Williams and Duncan Bassett, Imperial College London
Prof Ian Clark, University of East Anglia
Dr Stephen Robinson, Quadram Institute
Prof Andrea Barbero, University of Basel
Prof Sandra Poliselli Farsky, University of Sao Paolo
Indicators of esteem
2019: University of Surrey Researcher of the Year, runner up
2014: New Investigator Award, Osteoarthritis Research Society International
2011-present: reviewer for: Frontiers Bioengineering and Biotechnology, Stem Cells Reports, Scientific reports, Annals of Rheumatic diseases, Arthritis and Rheumatology, Arthritis Research and Therapy, Osteoarthritis and Cartilage, ECM, Tissue Engineering, Cartilage, PLOS one, Journal of Physiology, Journal of British Pharmacology
Research interests
I lead a research group focussed in understanding the molecular mechanisms associated with the pathogenesis of osteoarthritis (OA). OA is a musculoskeletal condition characterised by degeneration of the articular cartilage and abnormal bone remodelling. Despite being a high disabling disease, only symptomatic treatment is currently available to patients until surgical joint replacement is required. The lack of non-invasive therapeutic treatments is linked to the poor understanding of OA pathogenesis and consequently to the lack pro-regenerative pharmacological targets.
Our goal is to better understand OA pathogenesis to drive the development of new drugs to treat OA.
To this end we are working on four different areas:
1) We aim to characterise the role of microRNAs in the modulation of the Wnt signalling in the articular cartilage. The Wnt signalling plays a pivotal role in regenerative processes and it is de-regulated in OA (Nalesso et al, JCB 2011; Nalesso et al., Annals of Rheumatic Diseases 2017). We want to identify the molecular drivers regulating its homeostasis in physiological conditions to re-establish their function in disease. This work is in collaboration with the McCormick's group at Queen Mary University of London and has been funded through a New Investigator Research Grant awarded by the MRC in 2019.
2) We are investigating the role of Calcium Calmodulin Kinase II (CaMKII) in the modulation of lipid metabolism in OA. We have shown that CaMKII inhibition exacerbate OA progression in animal models of OA and this was associated with metabolic changes in the articular cartilage (Nalesso et al., JCB 2011; Nalesso et al. Sci Rep 2021). We aim to define new therapeutic targets by characterising the link between altered cell metabolism and tissue degeneration. Two PhD studentships have been funded under this research topic through funds awarded by the Academy of Medical Sciences Springboard Award, the Longhurst Legacy Fund and the UoS Doctoral College. The projects are in partnership with Dr Fielding at the School of Biosciences (UoS) and Prof Campanella at the RVC.
3) We want to determine key age-associated changes in the extracellular matrix of the articular cartilage to develop new ex-vivo models to study how aging affects signalling in the tissue and modify the response to drugs. This will help in reducing the use of animals in pre-clinical studies and will inform the development of more effective drugs for aged patients, who are the mostly affected by OA. This project is one of five studentships awarded by the Dunhill Medical Trust as part of the Engineering novel in-vitro Model systems to accelERate aGEing research doctoral training programme (EMERGE DTP).
4) We want to investigate whether environmental conditions and exposure to pollutants can affect cartilage health and the development of OA. This will lead to preventative measures aimed to reduce the number of people affected by OA and/or to slow down disease progression. This work is in collaboration with Prof FArsky's laboratory at the University of Sao Paulo.
Research collaborations
Dr Kamalan Jeevaratnam, Prof Barbara Fielding, Dr Paola Campagnolo, University of Surrey
Mrs Kathryn Gill, Royal Surrey County Hospital
Dr Peter McCormick and Prof Francesco dell’Accio, Queen Mary University of London
Prof Michelangelo Campanella, Royal Veterinary College
Profs Graham Williams and Duncan Bassett, Imperial College London
Prof Ian Clark, University of East Anglia
Dr Stephen Robinson, Quadram Institute
Prof Andrea Barbero, University of Basel
Prof Sandra Poliselli Farsky, University of Sao Paolo
Indicators of esteem
2019: University of Surrey Researcher of the Year, runner up
2014: New Investigator Award, Osteoarthritis Research Society International
2011-present: reviewer for: Frontiers Bioengineering and Biotechnology, Stem Cells Reports, Scientific reports, Annals of Rheumatic diseases, Arthritis and Rheumatology, Arthritis Research and Therapy, Osteoarthritis and Cartilage, ECM, Tissue Engineering, Cartilage, PLOS one, Journal of Physiology, Journal of British Pharmacology
Supervision
Postgraduate research supervision
Mr Nick Day, Role of CaMKII in lipid metabolism in the articular cartilage and OA
Miss Mia Mohammed, Generation of a novel in vitro system to investigate the effect of aging on the articular cartilage
Teaching
Currently teaching Cell and Molecular Biology within the module VMS1003
Publications
Highlights
● Scucuglia Heluany C, Barbim Donate P, Henriques Schneider A, Fabris AL, Gomes RA, Villas-Boas IM, Vilarinho Tambourgi D, Aparecida Silva T, Goulart Trossini GH, Nalesso G, Lani Volpe Silveira E, Queiroz Cunha F, Poliselli 4 Farsky SH, Hydroquinone exposure worsens rheumatoid arthritis through the activation of the aryl hydrocarbon receptor and interleukin-17 pathways. Antioxidants 2021, Accepted, in press
● Thomas BL, Nosrati B, Alvarez M, Thorup AS, Nalesso G, Caxaria S, Eldridge SE, Barawi A, Nicholson JG, Perretti M, Gaston-Muassett C, Maloney A, Moore A, Jupp R, Dell’Accio F WNT3A-loaded exosomes enable cartilage repair. J Extracell Vesicles. 2021 May;10(7):e12088. doi: 10.1002/jev2.12088. Epub 2021 May 19. ● Nalesso G# , Thorup AS, Eldridge SE, de Palma A, Kaur A, Peddireddi K, Blighe K, Rana S, Stott B, Vincent TL, Balu S, Thomas BL, Bertrand J, Sherwood, J, Fioravanti A, Achan P, Pitzalis C, Dell’Accio F, Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis. Sci rep, 2021 Mar 11;11(1):5682. doi: 10.1038/s41598-021-82067-w.
● Thorup AS, Strachan D, Caxaria S, Poulet B, Thomas BL, Eldridge SE, Nalesso G, Whiteford J, Pitzalis C, Aigner T , Corder R, Bertrand J and Dell’Accio F. ROR2 blockade as a therapy for osteoarthritis. Sci Transl Med 2020 Sep 16;12(561):eaax3063.doi: 10.1126/scitranslmed.aax3063. ● Budd E, Nalesso G, Mobasheri A. Extracellular genomic biomarkers of osteoarthritis. Expert Rev Mol Diagn. 2018 Jan;18(1):55-74. doi: 10.1080/14737159.2018.1415757. Epub 2017 Dec 15.
● Rahmati M, Nalesso G, Mobasheri A, Mozafari M. Aging and Osteoarthritis: Central Role of the Extracellular Matrix. Ageing Res Rev. 2017 Jul 31. pii: S1568-1637(16)30284-7. doi: 10.1016/j.arr.2017.07.004. [Epub ahead of print] Review.
● Nalesso G*, Thomas BL, Yu Y, Sherwood JC, Yu J, Addimanda O, Eldridge SE, Thorup AS, Dale L, Schett G, Zwerina J, El Tawil N, Pitzalis C, Dell’Accio F. Wnt16 antagonizes excessive canonical WNT activation and protects cartilage in osteoarthritis. Ann Rheum Dis. 2017 Jan;76(1):218-226. doi: 10.1136/annrheumdis-2015-208577.
● Eldridge S, Nalesso G, Ismail H, Vicente-Greco K, Kabouridis P, Ramachandran M, Niemeier A, Herz J, Pitzalis C, Perretti M, Dell’Accio F. Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Ann Rheum Dis. 2015 Aug
● Sherwood J, Bertrand J, Nalesso G, Poulet B, Pitsillides A, Brandolini L, Karystinou A, De Bari C, Luyten FP, Pitzalis C, Pap T, Dell'Accio F. A homeostatic function of CXCR2 signalling in articular cartilage. Ann Rheum Dis. 2014 Aug 18
● Greco KV*, Nalesso G*, Kaneva MK, Sherwood J, Iqbal AJ, Moradi-Bidhendi N, Dell'Accio F, Perretti M. Analyses on the mechanisms that underlie the chondroprotective properties of calcitonin. Biochem Pharmacol. 2014 Aug 9
● Heywood HK, Nalesso G, Lee DA, Dell'accio F. Culture expansion in low-glucose conditions preserves chondrocyte differentiation and enhances their subsequent capacity to form cartilage tissue in three-dimensional culture. Biores Open Access. 2014 Feb 1
● Slack RJ, Russell L, Barton NP, Weston C, Nalesso G, Thompson S-A, Allen M, Chen YH, Barnes A, Hodgson ST, Hall DA. Antagonism of human CC-chemokine receptor 4 can be achieved through three distinct binding sites on the receptor.Pharma Pharmacology research and Perspectives 30 DEC 2013 ● Bertrand J, Stange R, Hidding H, Echtermeyer F, Nalesso G, Godmann L, Timmen M, Bruckner P, Dell'accio F, Raschke MJ, Pap T, Dreier R. Bone fracture repair, but not fetal skeletal development is supported by syndecan-4. Arthritis Rheum. 2012 Dec 11
● Bertrand J, Nitschke Y, Fuerst M, Hermann S, Schäfers M, Sherwood J, Nalesso G, Ruether W, Rutsch F, Dell'accio F, Pap T Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice.. Ann Rheum Dis. 2012
● Greco KV, Iqbal AJ, Rattazzi L, Nalesso G, Moradi-Bidhendi N, Moore AR, Goldring MB, Dell’Accio F, Perretti M. High density micromass cultures of a human chondrocyte cell line: a reliable assay system to reveal the modulatory functions of pharmacological agents. Biochem Pharmacol. 2011 Dec 15
● Nalesso G; Sherwood J, Bertrand J, Pap T, Ramachandran M, De Bari C, Pitzalis C, Dell’Accio F. “WNT-3A modulates articular chondrocyte phenotype by activating both canonical and noncanonical pathways”., J Cell Biol.,2011 May; 193: 551-564. This paper attracted a comment from Kestler and Kuhl in the same issue (J Cell Biol., 2011 May; 193: 431-3) and has been selected as editor’s choice in a comment by Gough in Science Signalling (Sci Signal., 2011 May; 172:ec134).
● Brunati AM, Tibaldi E, Carraro A, Gringeri E, D'Amico F Jr, Toninello A, Massimino ML, Pagano MA, Nalesso G, Cillo U. Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures. Biochim Biophys Acta. 2008 Mar; 1783(3):347-5.5 *co-first authorship; # corresponding author
• Nalesso G*, Thomas BL*, Yu Y, Sherwood JC, Yu J, Addimanda O, Eldridge SE, Thorup AS, Dale L, Schett G, Zwerina J, El Tawil N, Pitzalis C, Dell'Accio F. Wnt16 antagonizes excessive canonical WNT activation and protects cartilage in osteoarthritis. Ann Rheum Dis. 2016 May 4. pii: annrheumdis-2015-208577. doi: 10.1136/annrheumdis-2015-208577. [Epub ahead of print]
• Eldridge S, Nalesso G, Ismail H, Vicente-Greco K, Kabouridis P, Ramachandran M, Niemeier A, Herz J, Pitzalis C, Perretti M, Dell'Accio F. Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Ann Rheum Dis. 2015 Aug
• Sherwood J, Bertrand J, Nalesso G, Poulet B, Pitsillides A, Brandolini L, Karystinou A, De Bari C, Luyten FP, Pitzalis C, Pap T, Dell'Accio F. A homeostatic function of CXCR2 signalling in articular cartilage. Ann Rheum Dis. 2014 Aug 18
• Greco KV*, Nalesso G*, Kaneva MK, Sherwood J, Iqbal AJ, Moradi-Bidhendi N, Dell'Accio F, Perretti M. Analyses on the mechanisms that underlie the chondroprotective properties of calcitonin. Biochem Pharmacol. 2014 Aug 9
• Heywood HK, Nalesso G, Lee DA, Dell'accio F. Culture expansion in low-glucose conditions preserves chondrocyte differentiation and enhances their subsequent capacity to form cartilage tissue in three-dimensional culture. Biores Open Access. 2014 Feb 1
• Slack RJ, Russell L, Barton NP, Weston C, Nalesso G, Thompson S-A, Allen M, Chen YH, Barnes A, Hodgson ST, Hall DA. Antagonism of human CC-chemokine receptor 4 can be achieved through three distinct binding sites on the receptor.Pharma Pharmacology research and Perspectives 30 DEC 2013
• Bertrand J, Stange R, Hidding H, Echtermeyer F, Nalesso G, Godmann L, Timmen M, Bruckner P, Dell'accio F, Raschke MJ, Pap T, Dreier R. Bone fracture repair, but not fetal skeletal development is supported by syndecan-4. Arthritis Rheum. 2012 Dec 11
• Bertrand J, Nitschke Y, Fuerst M, Hermann S, Schäfers M, Sherwood J, Nalesso G, Ruether W, Rutsch F, Dell'accio F, Pap T Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice.. Ann Rheum Dis. 2012 Apr 17
• Greco KV, Iqbal AJ, Rattazzi L, Nalesso G, Moradi-Bidhendi N, Moore AR, Goldring MB, Dell'Accio F, Perretti M. High density micromass cultures of a human chondrocyte cell line: a reliable assay system to reveal the modulatory functions of pharmacological agents. Biochem Pharmacol. 2011 Dec 15
• Nalesso G; Sherwood J, Bertrand J, Pap T, Ramachandran M, De Bari C, Pitzalis C, Dell'Accio F. “WNT-3A modulates articular chondrocyte phenotype by activating both canonical and noncanonical pathways”., J Cell Biol.,2011 May; 193: 551-564. This paper attracted a comment from Kestler and Kuhl in the same issue (J Cell Biol., 2011 May; 193: 431-3) and has been selected as editor's choice in a comment by Gough in Science Signalling (Sci Signal., 2011 May; 172:ec134).
• Brunati AM, Tibaldi E, Carraro A, Gringeri E, D'Amico F Jr, Toninello A, Massimino ML, Pagano MA, Nalesso G, Cillo U. Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures. Biochim Biophys Acta. 2008 Mar; 1783(3):347-5.