Gruppo Paoli
Laboratory of Enzymology, Drug Discovery and Protein targeting
Coordinator
Prof. Paolo Paoli
Brief Biographical sketch of the Coordinator
Master degree in Biology in 1993 at the University of Florence with grade 110/110 cum laude.
Post-graduate studies in Biochemistry and Clinical Chemistry (scuola di specializzazione in Biochimica e Chimica clinica) in November 1997
PhD in Biochemistry in March 2002
In November 2002 Researcher (Biochemistry, BIO/10) at the Faculty of Sciences of the University of Firenze.
July 2018: associate professor in BIO/10.
In December 2018 he obtained the Abilitazione Nazionale to Full Professor in 05/E Biochemistry
From 2020 to 2024 Prof. Paoli held the role of coordinator of the Biochemistry section of the Department
Member of the Scientific Board the Doctorate/Phd Program in
PhD School in Biochemistry and Molecular Biology (BiBiM 2.0)
Member of the following Scientific Societis
SIB
Member of editorial board of the following Journals
Biomolecules
Frontiers in Nutrition
Research Team
Dott. Rebecca Sodano
Technician: Dott. Alice Santi
Prof.ssa Anna Caselli
Prof. Francesco Bemporad
Several thesis students attending the Biology and Chemistry courses
Current research interest
The role of Protein tyrosine Phosphatases in regulating cell growth and metabolism, metabolic diseases such as type two diabetes and obesity, the molecular mechanisms that contributes to the onset of drug resistance, the development of multitarget drugs, protein targeting, the mechanism of action of natural compounds, the impact of microplastic and plasticizers on human cells.
Current/recent sources of funding
Drug resistance, type two diabetes, cell metabolism, multitarget drugs, insulin resistance and enzymology
10 best pubblications of the last 5 years
- Davighi MG, Clemente F, Matassini C, Cacciarini M, Tanini D, Goti A, Morrone A, Paoli P, Cardona F. Acetal functionalized iminosugars for targeting β-glucocerebrosidase modulation. Eur J Med Chem. 2025 Jun 5;290:117529. doi: 10.1016/j.ejmech.2025.117529. Epub 2025 Mar 19. PMID: 40174262.
- Laghezza A, Falbo E, Gilardi F, Thomas A, Brunetti L, Leuci R, Piemontese L, Tortorella P, Biswas A, Singh RP, Pattnaik AK, Jayaprakash V, Tambe S, Ca S, Wackerlig-Damle J, Paoli P, Loiodice F, Lavecchia A. A new potent and selective peroxisome proliferator-activated receptor alpha partial agonist displays anti-steatotic effects In vitro and behaves as a safe hypolipidemic and hypoglycemic agent in a diabetic mouse model. Eur J Med Chem. 2025 May 5;289:117494. doi: 10.1016/j.ejmech.2025.117494. Epub 2025 Mar 11. PMID: 40088662.
- Kousaxidis A, Paoli P, Kovacikova L, Genovese M, Santi A, Stefek M, Petrou A, Nicolaou I. Rational design and synthesis of novel N-benzylindole-based epalrestat analogs as selective aldose reductase inhibitors: An unexpected discovery of a new glucose-lowering agent (AK-4) acting as a mitochondrial uncoupler. Eur J Med Chem. 2025 Jan 5;281:117035. doi: 10.1016/j.ejmech.2024.117035. Epub 2024 Nov 8. PMID: 39536493.
- Pranzini E, Muccillo L, Nesi I, Santi A, Mancini C, Lori G, Genovese M, Lottini T, Comito G, Caselli A, Arcangeli A, Sabatino L, Colantuoni V, Taddei ML, Cirri P, Paoli P. Limiting serine availability during tumor progression promotes muscle wasting in cancer cachexia. Cell Death Discov. 2024 Dec 21;10(1):510. doi: 10.1038/s41420-024-02271-1. PMID: 39706853; PMCID: PMC11662032.
- Laghezza A, Cerchia C, Genovese M, Montanari R, Capelli D, Wackerlig J, Simic S, Falbo E, Pecora L, Leuci R, Brunetti L, Piemontese L, Tortorella P, Biswas A, Singh RP, Tambe S, Sudeep CA, Pattnaik AK, Jayaprakash V, Paoli P, Lavecchia A, Loiodice F. A chemical modification of a peroxisome proliferator-activated receptor pan agonist produced a shift to a new dual alpha/gamma partial agonist endowed with mitochondrial pyruvate carrier inhibition and antidiabetic properties. Eur J Med Chem. 2024 Sep 5;275:116567. doi: 10.1016/j.ejmech.2024.116567.
- Davighi MG, Clemente F, Andreasen ES, Nielsen MB, Matassini C, Goti A, Morrone A, Paoli P, Cardona F, Cacciarini M. Iminosugar-Dihydroazulenes as Mutant L444P Glucocerebrosidase Enhancers. Chem Biodivers. 2024 Aug;21(8):e202401104. doi: 10.1002/cbdv.202401104. Epub 2024 Jul 23. PMID: 38847390.
- Maccari R, Wolber G, Genovese M, Sardelli G, Talagayev V, Balestri F, Luti S, Santi A, Moschini R, Del Corso A, Paoli P, Ottanà R. Designed multiple ligands for the treatment of type 2 diabetes mellitus and its complications: Discovery of (5-arylidene-4-oxo-2-thioxothiazolidin-3-yl)alkanoic acids active as novel dual-targeted PTP1B/AKR1B1 inhibitors. Eur J Med Chem. 2023 Apr 5;252:115270. doi: 10.1016/j.ejmech.2023.115270. Epub 2023 Mar 14. PMID: 36934484.
- Laghezza A, Cerchia C, Genovese M, Leuci R, Pranzini E, Santi A, Brunetti L, Piemontese L, Tortorella P, Biswas A, Singh RP, Tambe S, Ca S, Pattnaik AK, Jayaprakash V, Paoli P, Lavecchia A, Loiodice F. A New Antidiabetic Agent Showing Short- and Long-Term Effects Due to Peroxisome Proliferator-Activated Receptor Alpha/Gamma Dual Agonism and Mitochondrial Pyruvate Carrier Inhibition. J Med Chem. 2023 Mar 9;66(5):3566-3587. doi: 10.1021/acs.jmedchem.2c02093. Epub 2023 Feb 15. PMID: 36790935.
- Casertano M, Genovese M, Santi A, Pranzini E, Balestri F, Piazza L, Del Corso A, Avunduk S, Imperatore C, Menna M, Paoli P. Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara. Pharmaceutics. 2023 Feb 4;15(2):528. doi: 10.3390/pharmaceutics15020528. PMID: 36839851; PMCID: PMC9964544.
- Nesi I, Della Bella C, Taddei ML, Santi A, Pranzini E, Paoli P, D'Elios MM, Ramazzotti M, Genovese M, Caselli A, Cirri P. Targeting of tumor cells by custom antigen transfer: a novel approach for immunotherapy of cancer. Front Oncol. 2023 Oct 13;13:1245248. doi: 10.3389/fonc.2023.1245248. PMID: 37901327; PMCID: PMC10612144.
Previeus research experiences
Prof Paoli collaborate with several italian and interantional researchers
Main scientific contributions
Since 1993, Dr. Paoli has conducted research across several fields, including enzymology, drug discovery, molecular and cellular biology, cell signaling, and cancer research. His main research activities have focused on the following topics:
- Investigation of the catalytic mechanisms of low-molecular-weight phosphomonoesterases, enzymes involved in the regulation of key cellular processes such as cell growth and differentiation.
- Evaluation of the physiological roles of these enzymes in cellular systems and their involvement in the regulation of apoptosis, cell proliferation, and differentiation.
- Investigation of the factors affecting protein conformational stability and the role of post-translational modifications in promoting protein aggregation.
- Identification and characterization of novel enzyme inhibitors for the treatment of type 2 diabetes. This research led to the discovery of both natural and synthetic compounds exhibiting insulin-mimetic or insulin-sensitizing properties.
- Investigation of cancer cell metabolism and the molecular mechanisms underlying the development of chemoresistant phenotypes.
- Development of innovative drug-delivery systems based on carbon nanotubes for the targeted delivery of anticancer agents into tumor cells resistant to conventional chemotherapy.
- Characterization of novel pharmacological chaperones with therapeutic potential for the treatment of lysosomal storage disorders, including Gaucher disease.
- Investigation of the properties of elastomeric films as biomaterial scaffolds to support skeletal muscle cell growth for applications in regenerative medicine.
- Identification and characterization of compounds capable of acting as chemo- and radiosensitizers in tumor cells resistant to conventional anticancer therapies, including melanoma and colorectal cancer models.
- Investigation of the impact of microplastics on the metabolism of human cells.
Collaborations
Prof Stefano Cicchi, Prof Francesca Cardona, Prof Claudia Giorgi, Dipartimento di Chimica “Ugo Schiff”
Dott. Camilla Parmeggiani, European Laboratory for Non-Linear Spectroscopy, (LENS)
Prof Amelia Morrone, Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze;
Prof. Giovanna Caderni, Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze;
Prof. Mario Milco D’Elios, Dipartimento di Medicina Sperimentale e Clinica)
Prof. Nadia Mulinacci, Dipartimento di Neuroscienze, Area del Farmaco e Salute del Bambino (NEUROFARBA)
Prof.ssa Marta Ferraroni, Dipartimento di Chimica (Università di Firenze)
Prof. Rosaria Ottanà Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università degli Studi di Messina;
Prof Antonella del Corso, Università degli Studi di Pisa
Prof Marco Vanoni, Università degli Studi di Milano-Bicocca
Prof. Marialuisa Menna, Dipartimento di Farmacia, Università Federico II di Napoli
Prof. Samuel Enoch Estrada-Soto, Universidad Autonoma del estado de Morelos, Cuernavaca, Morelos 62209, Mexico;
Prof. Gerhard Wolber, Institute of Pharmacy, Computer-Aided Molecular Design, Freie Universitaet Berlin, Koenigin-Luisestr, 14195 Berlin, Germany
Dott.ssa Federica Pisaneschi, Department of Cancer Systems Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX
Ultimo aggiornamento
15.07.2026