School of Medicine

Research interest

Dr. Vangelista has knowledge and skills in several biomedical and basic science areas such as biochemistry, molecular, structural and cell biology, biocomputing, microbiology, immunology and virology. His major field of expertise is recombinant protein design, engineering, expression and purification. As PI, he succeeded in obtaining competitive grants from major international agencies (EU, NIH, and NATO) but also national grants (Italian and Kazakh). He authored several international peer review articles, reviews and book chapters, with an H index of 23 (Scopus). He is inventor in 2 patents, reviewer for several international journals and grant agencies and Editor for the World Allergy Organization Journal.

Recent research by Dr. Vangelista dealt with the development of CCL5-based HIV-1 entry inhibitors, IgE as anti-tumor agent and the engineering of commensal bacteria for the in vivo delivery of therapeutic proteins.

Current and future research spans protein engineering, molecular biology, biochemistry, immunology and microbiology, reflecting the integrated approach adopted to address the development of innovative diagnostic, preventive and therapeutic strategies.

With the design, production and characterization of novel CCL5 derivatives acting as CCR5 antagonists and potent HIV-1 blockers, a new biomedical avenue has been opened. CCR5 is a key receptor for a growing number of infectious and inflammatory diseases. Therefore, potent CCR5 blockers based on CCL5 are now being exploited for a number of pathologies, including but not limited to cancer, inflammatory bowel disease, S. aureus LukED toxin inhibition and of course HIV-1 infection inhibition.

Project(s) for intake 2021:

Harnessing the CCL5:CCR5 axis to explore its therapeutic landscape

 This project stems from a long lasting research on the development of CCL5 derivatives providing potent HIV-1 entry inhibition by blocking CCR5. CCR5 is a chemokine receptor at the centre of attention for being the main HIV-1 co-receptor and for its role in a multitude of inflammation-related conditions and infectious diseases (1), and CCL5 is a chemokine ligand of CCR5, most studied for the engineering of HIV-1 blockers (2).

We developed a number of full-length CCL5 derivatives that showed antagonist, as well as agonist activity on CCR5 and that exhibited unprecedented anti-HIV-1 potency in cellular assays (3). Thanks to the solution of the three-dimensional structure of the complex between CCR5 and a potent CCL5 derivative (4), we rationally designed new point mutations on our CCL5 derivatives, aimed at optimizing the occupancy of the chemokine binding cavity in CCR5 (5). We are now producing the new CCL5 variants and wish to establish a novel cell-based CCR5 system to test their potency. In parallel (within collaborative projects), we are testing the effect of the CCL5 variants on inflammatory bowel disease and cancer and wish to expand on these directions as well as on other pathologies where CCR5 blockade may play a perspective therapeutic role. We also consider the production of the CCL5 derivatives by engineered commensal bacteria as this may constitute a therapeutic horizon that lies beyond HIV-1 live microbicides (6).

 References

 Vangelista L & Vento S (2018) Front Immunol 8:1981

1. Vangelista L et al. (2008) Vaccine 26:3008-15
2. Secchi M et al. (2018) Sci Rep 8:1890
3. Zheng Y et al. (2017) Immunity 46:1005-17
4. Kalikanova Y & Vangelista L (2021) In preparation
5. Vangelista L et al. (2010) Antimicrob Agents Chemother 54:2994-3001

Supported by the Faculty Development Competitive Research Grant “Expanding the therapeutic landscape of CCR5 blockade and CCL5 engineering” (021220FD2551 2021-2023) to Luca Vangelista.