Alessio Ciulli

FRSE FRSC
Born (1977-07-22) 22 July 1977
Florence, Italy
NationalityItalian British
Alma materUniversity of Florence(laurea), University of Cambridge(PhD)
Scientific career
FieldsTargeted Protein Degradation, Chemical Biology
InstitutionsUniversity of Dundee
Thesis
Doctoral advisorsChris Abell
Websitehttps://www.lifesci.dundee.ac.uk/people/alessio-ciulli-0; https://www.dundee.ac.uk/cetpd

Alessio Ciulli FRSE FRSC (born in Firenze, 22 July 1977) is an Italian British biochemist. Currently, he is the Professor of Chemical & Structural Biology at the School of Life Sciences, University of Dundee, where he founded and directs Dundee' new Centre for Targeted Protein Degradation (CeTPD). He is also the scientific co-founder and advisor of Amphista Therapeutics.[1]

Educational background

Alessi Ciulli attended University of Florence in his hometown with an undergraduate laurea in chemistry and graduated magna cum laude. Under the late Prof Ivano Bertini, his final year laurea project was in computational drug design and NMR spectroscopy of matrix metalloproteases.[2] Awarded with a Gates Cambridge Scholarship, he did his PhD under the supervision of the late Professor Chris Abell at the University of Cambridge and in collaboration with Astex Technology ( now Astex Pharmaceuticals ) produced a thesis concerned with studying weak protein-ligand interactions using biophysical and structural methods.

Career

Ciulli remained in Cambridge University to conduct post-doctoral research on fragment-based drug discovery with Professor Abell and Professor Tom L. Blundell, under a College Junior Research Fellowship. Between February and June 2009, Ciulli went to Yale University as Human Frontier Science Programme visiting fellow to visit the laboratory of Professor Craig Crews before returning to Cambridge University to start his independent research career.[3] While at Cambridge, Ciulli was the group leader in the Department of Chemistry, Director of Studies in Chemistry and BBSRC David Phillis Fellow at Christ's College. In April 2013, he took up a Readership in Chemical & Structural Biology as a principal investigator within the Division of Biological Chemistry and Drug Discovery in the University of Dundee. Ciulli was promoted as the Professor of Chemical & Structural Biology in the same division in October 2016. In 2017, he co-founded Amphista Therapeutics, a company that focuses on developing drugs based on targeted protein degradation.[1] He was elected to the Fellowship of the Royal Society of Edinburgh in 2023.

Research

With his team in the Ciulli laboratory, Ciulli's works aim to develop small molecules inducing targeted protein degradation and modulating protein-protein interactions. One example of this type of work is the discovery of proteolysis-targeting chimera or PROTAC and its therapeutic potential.[4][5] Recruitment of an E3 ligase to the target protein by the PROTAC is a critical step in the mechanism of action, because it triggers the target protein to be ubiquitinated and then degraded by the proteasome. Ciulli and his colleagues were the first to produce an X-ray crystal structure of a class of PROTAC simultaneously bound to the target protein and the E3 ubiquitin ligase.[6] Much of Ciulli's research also contributed to studies on the Von Hippel-Lindau protein E3 ligase, especially in targeting the E3 ligase with small molecules.[7][8][9][10] In general, Ciulli's scientific contributions focus on targeted protein degradation (TPD) as a therapeutic modality in cancer and other diseases. His works on TPD led to the founding of Amphista Therapeutics. Amongst the other scientific accomplishments and discoveries of his laboratory, is the development of a chemical-genetic “bump and hole” approach in which Ciulli and colleagues designed an engineered mutant variant of BET bromodomains able to accommodate selectively its binding ligand, enabling the individual roles of BET proteins to be elucidated.

Awards

References

  1. 1 2 "Our Foundations". Amphista Therapeutics. Retrieved 2022-03-28.
  2. ↑ Gray, Harry Barkus; Banci, Lucia; Luchinat, Claudio; Turano, Paola (September 2012). "Ivano Bertini 1940–2012" (PDF). Nature Structural & Molecular Biology. 19 (9): 868–869. doi:10.1038/nsmb.2369. S2CID 22004688.
  3. ↑ "Alessio Ciulli". ORCID. Retrieved 2022-03-28.
  4. ↑ Scudellari, Megan (20 March 2019). "Protein-slaying drugs could be the next blockbuster therapies". Nature. 567 (7748): 298–300. Bibcode:2019Natur.567..298S. doi:10.1038/d41586-019-00879-3. PMID 30894734. S2CID 84186557.
  5. ↑ Zengerle, Michael; Chan, Kwok-Ho; Ciulli, Alessio (21 August 2015). "Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4". ACS Chemical Biology. 10 (8): 1770–1777. doi:10.1021/acschembio.5b00216. PMC 4548256. PMID 26035625.
  6. ↑ Gadd, Morgan S.; Testa, Andrea; Lucas, Xavier; Chan, Kwok-Ho; Chen, Wenzhang; Lamont, Douglas J.; Zengerle, Michael; Ciulli, Alessio (May 2017). "Structural basis of PROTAC cooperative recognition for selective protein degradation". Nature Chemical Biology. 13 (5): 514–521. doi:10.1038/nchembio.2329. PMC 5392356. PMID 28288108.
  7. ↑ Van Molle, Inge; Thomann, Andreas; Buckley, Dennis L.; So, Ernest C.; Lang, Steffen; Crews, Craig M.; Ciulli, Alessio (October 2012). "Dissecting Fragment-Based Lead Discovery at the von Hippel-Lindau Protein:Hypoxia Inducible Factor 1α Protein-Protein Interface". Chemistry & Biology. 19 (10): 1300–1312. doi:10.1016/j.chembiol.2012.08.015. PMC 3551621. PMID 23102223.
  8. ↑ Galdeano, Carles; Gadd, Morgan S.; Soares, Pedro; Scaffidi, Salvatore; Van Molle, Inge; Birced, Ipek; Hewitt, Sarah; Dias, David M.; Ciulli, Alessio (23 October 2014). "Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities". Journal of Medicinal Chemistry. 57 (20): 8657–8663. doi:10.1021/jm5011258. PMC 4207132. PMID 25166285.
  9. ↑ Maniaci, Chiara; Hughes, Scott J.; Testa, Andrea; Chen, Wenzhang; Lamont, Douglas J.; Rocha, Sonia; Alessi, Dario R.; Romeo, Roberto; Ciulli, Alessio (10 October 2017). "Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation". Nature Communications. 8 (1): 830. Bibcode:2017NatCo...8..830M. doi:10.1038/s41467-017-00954-1. PMC 5635026. PMID 29018234.
  10. ↑ Cardote, Teresa A. F.; Ciulli, Alessio (21 September 2017). "Structure‐Guided Design of Peptides as Tools to Probe the Protein–Protein Interaction between Cullin‐2 and Elongin BC Substrate Adaptor in Cullin RING E3 Ubiquitin Ligases". ChemMedChem. 12 (18): 1491–1496. doi:10.1002/cmdc.201700359. PMC 5639367. PMID 28776949.
  11. ↑ "David Phillips fellows".
  12. ↑ "Alessio Ciulli awarded an ERC Starting Grant | Yusuf Hamied Department of Chemistry".
  13. ↑ "The EFMC Prizes for Young Medicinal Chemists".
  14. ↑ "ICBS Young Chemical Biologist Awards". International Chemical Biology Society.
  15. ↑ "Capps Green Zomaya Award". RSC Biological and Medicinal Chemistry Sector.
  16. ↑ "Dr Alessio Ciulli wins 2016 Emerging Investigator Lectureship – RSC Medicinal Chemistry Blog".
  17. ↑ "Drug Discovery Award for Alessio Ciulli". University of Dundee.
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