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Cell Stress & Death Lab

Aree di ricerca

The research activity is focused on the study and understanding of the molecular mechanisms underlying the cellular response to physiological and pathological stresses, capable of regulating the cellular 'adaptation / death' balance. To this end, ER Stress, autophagy, apoptosis and ferroptosis are the cellular processes studied with particular attention. This analysis is also aimed at identifying new potential therapeutic targets for the treatment of the pathologies under study.

A new line of research has recently been launched aimed at studying the role of the intestinal microbiota in the onset, progression and response to therapies in various human pathologies and, at the same time, evaluating its potential therapeutic role. Particular attention is paid to the study of bidirectional communication processes between microbiota and host, which involve the signaling pathways underlying the regulation of cellular 'adaptation/death' balance (ER stress, autophagy, apoptosis/ ferroptosis).

Our research uses in vitro (2D/3D cell culture), ex vivo (organ culture) and in vivo (animal) models.

Main research activities (ongoing)

Topic 1. Study of the molecular mechanisms regulating ferroptotic cell death and its use as a potential target in the therapeutic treatment of tumor and autoimmune diseases.

Topic 2. Role of ER Stress and Autophagy in the pathogenesis and treatment of human diseases characterized by gastrointestinal inflammation.

Topic 3. The gut microbiota: pathogenetic role and therapeutic target.

 

Cosgarea I, McConnell AT, Ewen T, Tang D, Hill DS, Anagnostou M, Elias M, Ellis RA, Murray A, Spender LC, Giglio P, Gagliardi M, Greenwood A, Piacentini M, Inman GJ, Fimia GM, Corazzari M, Armstrong JL, Lovat PE. Melanoma secretion of transforming growth factor-β2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration. Br J Dermatol. 2022 Apr;186(4):694-704. doi: 10.1111/bjd.20889. Epub 2021 Dec 27. PMID: 34773645.

Gagliardi M, Monzani R, Clemente N, Fusaro L, Saverio V, Grieco G, Pańczyszyn E, Yissachar N, Boccafoschi F, Corazzari M. A Gut-Ex-Vivo System to Study Gut Inflammation Associated to Inflammatory Bowel Disease (IBD). Biology (Basel). 2021 Jun 30;10(7):605. doi: 10.3390/biology10070605. PMID: 34209277; PMCID: PMC8301106.

Ferrari E, Monzani R, Saverio V, Gagliardi M, Pańczyszyn E, Raia V, Villella VR, Bona G, Pane M, Amoruso A, Corazzari M. Probiotics Supplements Reduce ER Stress and Gut Inflammation Associated with Gliadin Intake in a Mouse Model of Gluten Sensitivity. Nutrients. 2021 Apr 7;13(4):1221. doi: 10.3390/nu13041221. PMID: 33917155; PMCID: PMC8067866.

Gagliardi M, Clemente N, Monzani R, Fusaro L, Ferrari E, Saverio V, Grieco G, Pańczyszyn E, Carton F, Santoro C, Del Mare-Roumani S, Amidror S, Yissachar N, Boccafoschi F, Zucchelli S, Corazzari M. Gut-Ex-Vivo system as a model to study gluten response in celiac disease. Cell Death Discov. 2021 Mar 12;7(1):45. doi: 10.1038/s41420-021-00430-2. PMID: 33712560; PMCID: PMC7955131.

Gagliardi M, Saverio V, Monzani R, Ferrari E, Piacentini M, Corazzari M. Ferroptosis: a new unexpected chance to treat metastatic melanoma? Cell Cycle. 2020 Oct;19(19):2411-2425. doi: 10.1080/15384101.2020.1806426. Epub 2020 Aug 20. PMID: 32816618; PMCID: PMC7553499.

Gagliardi M, Cotella D, Santoro C, Corà D, Barlev NA, Piacentini M, Corazzari M. Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis. Cell Death Dis. 2019 Nov 28;10(12):902. doi: 10.1038/s41419-019-2143-7. PMID: 31780644; PMCID: PMC6883066.

Di Rienzo M, Antonioli M, Fusco C, Liu Y, Mari M, Orhon I, Refolo G, Germani F, Corazzari M, Romagnoli A, Ciccosanti F, Mandriani B, Pellico MT, De La Torre R, Ding H, Dentice M, Neri M, Ferlini A, Reggiori F, Kulesz-Martin M, Piacentini M, Merla G, Fimia GM. Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains. Sci Adv. 2019 May 8;5(5):eaau8857. doi: 10.1126/sciadv.aau8857. PMID: 31123703; PMCID: PMC6527439.

Giglio P, Gagliardi M, Bernardini R, Mattei M, Cotella D, Santoro C, Piacentini M, Corazzari M. Ecto-Calreticulin is essential for an efficient immunogenic cell death stimulation in mouse melanoma. Genes Immun. 2019 Jul;20(6):509-513. doi: 10.1038/s41435-018-0047-7. Epub 2018 Oct 4. PMID: 30282994.

Giglio P, Gagliardi M, Tumino N, Antunes F, Smaili S, Cotella D, Santoro C, Bernardini R, Mattei M, Piacentini M, Corazzari M. PKR and GCN2 stress kinases promote an ER stress-independent eIF2α phosphorylation responsible for calreticulin exposure in melanoma cells. Oncoimmunology. 2018 May 31;7(8):e1466765. doi: 10.1080/2162402X.2018.1466765. PMID: 30221067; PMCID: PMC6136861.

Corazzari M, Gagliardi M, Fimia GM, Piacentini M. Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate. Front Oncol. 2017 Apr 26;7:78. doi: 10.3389/fonc.2017.00078. PMID: 28491820; PMCID: PMC5405076.

Collaborazioni

 

 

Finanziamenti (ultimi 5 anni)
  • ‘Pediatric obesity and cardiovascular dysfunction: searching for early markers of damage’. [FAR - 2017]
  • ‘Role of the Apoptotic Repressor with CARD (ARC/Nol3) in the regulation of the Ferroptotic process: potential implications for Multiple Sclerosis treatment’ (AFeMuS). [FAR - 2019]
  • ‘The Microbiome as the interface between food and medicine: gut microbiota and microbiota-derived metabolites as potential active supplements in Alzheimer’s Disease’ (MiFoMAD - 2019). Progetti d’eccellenza (FOHN)
  • ‘Precision medicine for muscolo-skeletal regeneration, prosthetics, and active aging’ (PREMUROSA) [Horizon 2020 -2019]
  • ‘Twinning to excel materials engineering for medical devices’ (ExcellMater) [Horizon 2020 – 2020]
Membri

Responsabile: Prof. Marco Corazzari

Collaboratori: Dr Mara Gagliardi (PostDoc); Dr Romina Monzani (Assegnista); Dr Elzbieta Panczyszyn (PhD Student); Dr Valentina Saverio (PhD Student)​​​​​​​

Contacts: Marco Corazzari, marco.corazzari@uniupo.it

Location: Center for Translational Research on Autoimmune and Allergic Diseases (CAAD) – C.so Trieste 15°, Novara

 

 

Last modified 11 January 2024