GIULIANO PAGLIA

Dottore di ricerca

ciclo: XXXIV


supervisore: Professore Fabio Altieri
relatore: Professore Fabio Altieri

Titolo della tesi: Protein Disulfide-Isomerase A3 (PDIA3): a multifunctional protein as therapeutic target in several human diseases

Abstract Protein disulfide-isomerase associated 3 (PDIA3) plays an important role in the natural history of cancer and the development of therapeutic processes. As an ER chaperone, PDIA3 participates in MHC class I molecule assembly, regulates tumor cell immunogenicity, facilitates new glycoprotein synthesis. It functions as a 1,25D3-MARRS receptor, regulates gene transcription, binds to STAT3 and NF-κB, enhances MMC-induced DNA cross-linking and is involved in DNA repair processes and cytoskeletal remodeling. Numerous studies have demonstrated that PDIA3 plays a significant role in tumor development and chemoresistance in a wide variety of cancers, and it is involved in many other human pathologies, such as, neurodegenerative diseases, metabolic diseases, musculoskeletal system conditions, airway inflammations, platelet aggregation and viral infections. These crucial roles and their regulatory pathways might provide a framework for the comprehensive understanding of PDIA3 in human diseases, which might indicate its potential as a therapeutic target for cancer and other human diseases' treatment. During my thesis work, we deepened the role of punicalagin as a PDIA3 inhibitor, performing a comparative study with PDIA1. We also discovered two novelties, pulegone and myristicin, in terms of potentially leading compounds for PDIA3 inhibition. Our knowledge in terms of PDIA3’s binding sites and PDIA3’s ligands as potential inhibitors have allowed us to start a drug design project that is still underway to synthetically obtain the first specific inhibitor for PDIA3 that can meet the criteria of a good drug (Lipinsky’s rule of five). Furthermore, as proof of the value of having a PDIA3 inhibitor we used punicalagin, the best specific inhibitor of PDIA3 known so far, in two cellular models, prostate cancer and glioblastoma. Preliminary results on glioblastoma highlighted the punicalagin, as PDIA3’s inhibitor, to be a coadjutant in glioblastoma treatment with temozolomide. Our future goal will be to demonstrate, using in vitro and in vivo models, the role of PDIA3 synthetic inhibitors that can be implemented in new therapies for human diseases.

Produzione scientifica

11573/1669239 - 2023 - PDIA3 expression is altered in the limbic brain regions of triple-transgenic mouse model of Alzheimer's disease
Cassano, Tommaso; Giamogante, Flavia; Calcagnini, Silvio; Romano, Adele; Lavecchia, Angelo Michele; Inglese, Francesca; Paglia, Giuliano; Bukke, Vidyasagar Naik; Romano, Antonino Davide; Friuli, Marzia; Altieri, Fabio; Gaetani, Silvana - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 3005- - issn: 1422-0067 - wos: WOS:000932564000001 (5) - scopus: 2-s2.0-85148022809 (6)

11573/1697140 - 2023 - Design and synthesis of tetrahydro-β-carbolines derivatives as PDIA inhibitors.
Messore, A.; Madia, V. N.; Ialongo, D.; Patacchini, E.; Arpacioglu, M.; Scipione, L.; Altieri, F.; Paglia, G.; Meschiari, G.; Di Santo, R.; Costi, R. - 04f Poster
congresso: XXVIII edition of the National Meeting on Medicinal Chemistry (Chieti; Italy)
libro: XXVIII edition of the National Meeting on Medicinal Chemistry - ()

11573/1686701 - 2023 - Protein Disulfide Isomerase A3 (PDIA3): a pharmacological target in glioblastoma?
Paglia, Giuliano; Minacori, Marco; Meschiari, Giorgia; Fiorini, Sara; Chichiarelli, Silvia; Eufemi, Margherita; Altieri, Fabio - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 13279- - issn: 1422-0067 - wos: WOS:001060627600001 (0) - scopus: 2-s2.0-85170278840 (0)

11573/1609489 - 2022 - ERp57/PDIA3: new insight
Chichiarelli, Silvia; Altieri, Fabio; Paglia, Giuliano; Rubini, Elisabetta; Minacori, Marco; Eufemi, Margherita - 01g Articolo di rassegna (Review)
rivista: CELLULAR & MOLECULAR BIOLOGY LETTERS (CELLULAR & MOLECULAR BIOLOGY LETTERS, UNIV WROCLAW, INST BIOCHEM, DEPT GENETIC BIOCHEMISTRY, PRZBYSZEWSKIEGO 63/77, WROCLAW, POLAND, 51-148) pp. 12- - issn: 1425-8153 - wos: WOS:000750387500003 (21) - scopus: 2-s2.0-85123972536 (22)

11573/1618652 - 2021 - A comparative analysis of punicalagin interaction with PDIA1 and PDIA3 by biochemical and computational approaches
Paglia, G.; Antonini, L.; Cervoni, L.; Ragno, R.; Sabatino, M.; Minacori, M.; Rubini, E.; Altieri, F. - 01a Articolo in rivista
rivista: BIOMEDICINES (Basel : MDPI) pp. - - issn: 2227-9059 - wos: WOS:000807139700001 (3) - scopus: 2-s2.0-85118325939 (3)

11573/1549648 - 2021 - β-Hexachlorocyclohexane drives carcinogenesis in the human normal bronchial epithelium cell line BEAS-2B
Rubini, Elisabetta; Minacori, Marco; Paglia, Giuliano; Altieri, Fabio; Chichiarelli, Silvia; Romaniello, Donatella; Eufemi, Margherita - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 5834- - issn: 1422-0067 - wos: WOS:000660140100001 (2) - scopus: 2-s2.0-85106736428 (2)

11573/1592195 - 2021 - Tomato and olive bioactive compounds: a natural shield against the cellular effects induced by β-Hexachlorocyclohexane-activated signaling pathways
Rubini, Elisabetta; Minacori, Marco; Paglia, Giuliano; Macone, Alberto; Chichiarelli, Silvia; Altieri, Fabio; Eufemi, Margherita - 01a Articolo in rivista
rivista: MOLECULES (Basel: MDPI Berlin: Springer, 1996-) pp. 7135- - issn: 1420-3049 - wos: WOS:000735080100001 (4) - scopus: 2-s2.0-85121204399 (4)

11573/1461522 - 2020 - β-hexachlorocyclohexane: a small molecule with a big impact on human cellular biochemistry
Rubini, E.; Paglia, G.; Cannella, D.; Macone, A.; Di Sotto, A.; Gullì, Marco; Altieri, F.; Eufemi, M. - 01a Articolo in rivista
rivista: BIOMEDICINES (Basel : MDPI) pp. 1-17 - issn: 2227-9059 - wos: WOS:000592963700001 (15) - scopus: 2-s2.0-85096112816 (13)

11573/1268253 - 2019 - STAT3 post-translational modifications drive cellular signaling pathways in prostate cancer cells
Cocchiola, Rossana; Rubini, Elisabetta; Altieri, Fabio; Chichiarelli, Silvia; Paglia, Giuliano; Romaniello, Donatella; Carissimi, Stefania; Giorgi, Alessandra; Giamogante, Flavia; Macone, Alberto; Perugia, Giacomo; Gurtner, Aymone; Eufemi, Margherita - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1815- - issn: 1422-0067 - wos: WOS:000467648700013 (22) - scopus: 2-s2.0-85065334556 (22)

11573/1312818 - 2019 - Shmt2: a stat3 signaling new player in prostate cancer energy metabolism
Marrocco, Ilaria; Altieri, Fabio; Rubini, Elisabetta; Paglia, Giuliano; Chichiarelli, Silvia; Giamogante, Flavia; Macone, Alberto; Perugia, Giacomo; Magliocca, Fabio Massimo; Gurtner, Aymone; Maras, Bruno; Ragno, Rino; Patsilinakos, Alexandros; Manganaro, Roberto; Eufemi, Margherita - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. 1048- - issn: 2073-4409 - wos: WOS:000489103800107 (27) - scopus: 2-s2.0-85083913039 (25)

11573/1415977 - 2019 - PDIA3/ERp57, a multifunctional protein
Paglia, G; Eufemi, M; Cervoni, L; Chichiarelli, S; Giamogante, F; Carissimi, S; Rubini, E; Altieri, F - 04d Abstract in atti di convegno
congresso: 44th FEBS CONGRESS (Krakow, Poland)
libro: FEBS OPEN BIO, WILEY - ()

11573/1400461 - 2019 - beta-HEXACHLOROCYCLOHEXANE MAY INDUCE HORMONE RESISTANCE IN PROSTATE CANCER
Rubini, Elisabetta; Paglia, Giuliano; Altieri, Fabio; Chichiarelli, Silvia; Gullì, Marco; Pacelli Chiara, &Amp;; Eufemi, Margherita - 04d Abstract in atti di convegno
congresso: 2nd Workshop Differentiation and Neoplastic Transformation (Florence, Italy)
libro: Oral presentation - ()

11573/1180901 - 2018 - STAT3 is a hub protein of cellular signalling pathways triggered by persistent organochlorine pollutants (POPs)
Rubini, E.; Giamogante, F.; Carissimi, S.; Grieco, M.; Paglia, G.; Capauto, S.; Tedeschi, F.; Meconi, V.; Altieri, F.; Chichiarelli, S.; Eufemi, M. - 04d Abstract in atti di convegno
congresso: The 18th Young Scientists' Forum and 43rd FEBS Congress (Prague, Czech Republic)
libro: The 18th FEBS Young Scientists' Forum abstract book - ()

11573/1176788 - 2018 - STAT3, a hub protein of cellular signaling pathways, is triggered by β-hexaclorocyclohexane
Rubini, E; Altieri, F; Chichiarelli, S; Giamogante, F; Carissimi, S; Paglia, G; Macone, A; Eufemi, M - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 2108- - issn: 1422-0067 - wos: WOS:000442807400287 (8) - scopus: 2-s2.0-85050609617 (9)

11573/1180918 - 2018 - The role of AhR signalling pathways triggered by β-HCH in the progression of prostate cancer
Rubini, Elisabetta; Paglia, Giuliano; Giamogante, F.; Carissimi, S.; Meconi, V.; Pantaleone, V.; Ponza, R.; Chichiarelli, S.; Altieri, F.; Eufemi, M. - 04d Abstract in atti di convegno
congresso: XV FISV Congress (Rome, Italy)
libro: XV FISV CONGRESS Programme and Abstracts - ()

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