HIRSCH Emilio


Responsabile dell'U.O.

Cognome e Nome

HIRSCH Emilio

Qualifica

PO

Dipartimento

Biotecnologie Molecolari e Scienze per la Salute

Settore scientifico disciplinare

BIOLOGIA APPLICATA (BIO/13)

E-mail

emilio.hirsch@unito.it

Telefono

0116706425

Personale strutturato

Cognome e Nome

Giorgio Roberto Merlo

Qualifica

PA

Dipartimento

Biotecnologie Molecolari e Scienze per la Salute

Ente di appartenenza

Università di Torino

Cognome e Nome

Ghigo Alessandra

Qualifica

PA

Dipartimento

Biotecnologie Molecolari e Scienze per la Salute

Ente di appartenenza

Università di Torino

Cognome e Nome

Porporato Paolo Ettore

Qualifica

PA

Dipartimento

Biotecnologie Molecolari e Scienze per la Salute

Ente di appartenenza

Università di Torino

Personale non strutturato

Cognome e Nome

Liaci Carla

Qualifica

Ph.D student

Dipartimento

Biotecnologie Molecolari e Scienze per la Salute

Ente di appartenenza

Università di Torino

Cognome e Nome

Prever Lorenzo

Qualifica

Ph.D student

Dipartimento

Biotecnologie Molecolari e Scienze per la Salute

Ente di appartenenza

Università di Torino

Linee di ricerca

We elucidated the specific roles of class II PI3K isoforms in various contexts. For instance, our research indicates that PI3K-C2α is not only crucial for mouse embryo development but also plays a vital role in clathrindependent endocytosis and vesicle trafficking. We observed that the disruption of PI3K-C2α results in impaired embryonic development and disturbed intracellular transport, underscoring its significance in these processes. Additionally, our investigations have uncovered that PI3K-C2α is implicated in the activation of Rab11, a small GTPase that governs intracellular transport and recycling. These findings provide insights into the regulatory mechanisms mediated by PI3K-C2α in membrane trafficking. Furthermore, our investigations have revealed the significance of PI3K-C2α in the control of cell division, particularly in the context of breast cancer tumorigenesis. We have observed that altered expression or activity of PI3K-C2α impacts cell proliferation and division, suggesting its involvement in the regulation of these processes in cancer cells. Similarly, our studies have concentrated on the role of PI3K-C2β in mitosis progression, specifically in prostate cancer. Through our research, we have clarified the importance of PI3K-C2β in modulating mitotic events and ensuring proper cell division in prostate cancer cells. These findings shed light on the specific functions of PI3K-C2β in the context of cancer biology and provide a potential target for therapeutic interventions. More recently, our investigations have revealed an unexpected role of PI3K-C2β-mediated lipid signaling in the regulation of mTORC1-dependent neuronal excitability. We discovered that PI3K-C2β activity influences neuronal excitability in both mice and humans through its impact on mTORC1 signaling. This discovery highlights the involvement of class II PI3Ks in neuronal function and unveils a novel link between lipid signaling and neuronal excitability. Additionally, our research has clarified the subcellular localization of PI3K-C2γ on early endosomes, offering insights into its compartmentalization within the cell.

Tecnologie in uso dall'UO

  1. 1.
    Human iPSC-derived in vitro models
  2. 2.
    Organoids
  3. 3.
    Single-cell RNA sequencing
  4. 4.
    Generation of transgenic mouse lines
  5. 5.
    Generation of transgenic zebrafish lines
  6. 6.
    Confocal microscopy

Strumentazione

Denominazione

Leica SP8 Confocal microscope

Struttura ove la strumentazione è allocata

Dipartimento di Biotecnologie Molecolari e Scienze per la Salute

Responsabile

Emilio Hirsch

Pubblicazioni

  1. 1.
    Mina E, Wyart E, Sartori R, Angelino E, Zaggia I, Rausch V, Maldotti M, Pagani A, Hsu MY, Friziero A, 3 Sperti C, Menga A, Graziani A, Hirsch E, Oliviero S, Sandri M, Conti L, Kautz L, Silvestri L, Porporato PE. FK506 bypasses the effect of erythroferrone in cancer cachexia skeletal muscle atrophy. Cell Rep Med. 2023 Nov 28:101306. doi: 10.1016/j.xcrm.2023.101306. Epub ahead of print. PMID: 38052214.
  2. 2.
    Bandini C, Mereu E, Paradzik T, Labrador M, Maccagno M, Cumerlato M, Oreglia F, Prever L, Manicardi V, Taiana E, Ronchetti D, D'Agostino M, Gay F, Larocca A, Besse L, Merlo GR, Hirsch E, Ciarrocchi A, Inghirami G, Neri A, Piva R. Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma. Exp Hematol Oncol. 2023 Aug 10;12(1):71. doi: 10.1186/s40164-023-00434-x. PMID: 37563685; PMCID: PMC10413620.
  3. 3.
    Mastini C, Campisi M, Patrucco E, Mura G, Ferreira A, Costa C, Ambrogio C, Germena G, Martinengo C, Peola S, Mota I, Vissio E, Molinaro L, Arigoni M, Olivero M, Calogero R, Prokoph N, Tabbò F, Shoji B, Brugieres L, Geoerger B, Turner SD, Cuesta-Mateos C, D'Aliberti D, Mologni L, Piazza R, GambacortiPasserini C, Inghirami GG, Chiono V, Kamm RD, Hirsch E, Koch R, Weinstock DM, Aster JC, Voena C, Chiarle R. Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma. Sci Transl Med. 2023 Jun 28;15(702):eabo3826. doi: 10.1126/scitranslmed.abo3826. Epub 2023 Jun 28. PMID: 37379367.
  4. 4.
    Liu Q, Telezhkin V, Jiang W, Gu Y, Wang Y, Hong W, Tian W, Yarova P, Zhang G, Lee SM, Zhang P, Zhao M, Allen ND, Hirsch E, Penninger J, Song B. Electric field stimulation boosts neuronal differentiation of neural stem cells for spinal cord injury treatment via PI3K/Akt/GSK-3β/β-catenin activation. Cell Biosci. 2023 Jan 9;13(1):4. doi: 10.1186/s13578-023-00954-3. PMID: 36624495; PMCID: PMC9830810
  5. 5.
    Liaci C, Camera M, Zamboni V, Sarò G, Ammoni A, Parmigiani E, Ponzoni L, Hidisoglu E, Chiantia G, Marcantoni A, Giustetto M, Tomagra G, Carabelli V, Torelli F, Sala M, Yanagawa Y, Obata K, Hirsch E, Merlo GR. Loss of ARHGAP15 affects the directional control of migrating interneurons in the embryonic cortex and increases susceptibility to epilepsy. Front Cell Dev Biol. 2022 Dec 8;10:875468. doi: 10.3389/fcell.2022.875468. PMID: 36568982; PMCID: PMC9774038.
  6. 6.
    Rotolo R, Leuci V, Donini C, Galvagno F, Massa A, De Santis MC, Peirone S, Medico G, Sanlorenzo M, Vujic I, Gammaitoni L, Basiricò M, Righi L, Riganti C, Salaroglio IC, Napoli F, Tabbò F, Mariniello A, Vigna E, Modica C, D'Ambrosio L, Grignani G, Taulli R, Hirsch E, Cereda M, Aglietta M, Scagliotti GV, Novello S, Bironzo P, Sangiolo D. Novel Lymphocyte-Independent Antitumor Activity by PD-1 Blocking Antibody against PD-1+ Chemoresistant Lung Cancer Cells. Clin Cancer Res. 2023 Feb 1;29(3):621-634. doi: 10.1158/1078-0432.CCR-22-0761. PMID: 36165915; PMCID: PMC9890136.
  7. 7.
    Tocchetti CG, Ghigo A, Hirsch E. 'Circulating' RNA-based therapies in Cardio-Oncology. Eur Heart J. 2022 Nov 7;43(42):4512-4514. doi: 10.1093/eurheartj/ehac407. PMID: 35924283.
  8. 8.
    Gozzelino L, Kochlamazashvili G, Baldassari S, Mackintosh AI, Licchetta L, Iovino E, Liu YC, Bennett CA, Bennett MF, Damiano JA, Zsurka G, Marconi C, Giangregorio T, Magini P, Kuijpers M, Maritzen T, Norata GD, Baulac S, Canafoglia L, Seri M, Tinuper P, Scheffer IE, Bahlo M, Berkovic SF, Hildebrand MS, Kunz WS, Giordano L, Bisulli F, Martini M, Haucke V, Hirsch E, Pippucci T. Defective lipid signalling caused by mutations in PIK3C2B underlies focal epilepsy. Brain. 2022 Jul 29;145(7):2313-2331. doi: 10.1093/brain/awac082. PMID: 35786744; PMCID: PMC9337808.
  9. 9.
    De Santis MC, Gozzelino L, Margaria JP, Costamagna A, Ratto E, Gulluni F, Di Gregorio E, Mina E, Lorito N, Bacci M, Lattanzio R, Sala G, Cappello P, Novelli F, Giovannetti E, Vicentini C, Andreani S, Delfino P, Corbo V, Scarpa A, Porporato PE, Morandi A, Hirsch E, Martini M. Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer. Gut. 2023 Feb;72(2):360-371. doi: 10.1136/gutjnl-2021-325117. Epub 2022 May 27. PMID: 35623884; PMCID: PMC9872233.
  10. 10.
    Margaria JP, Moretta L, Alves-Filho JC, Hirsch E. PI3K Signaling in Mechanisms and Treatments of Pulmonary Fibrosis Following Sepsis and Acute Lung Injury. Biomedicines. 2022 Mar 23;10(4):756. doi: 10.3390/biomedicines10040756. PMID: 35453505; PMCID: PMC9028704.

Dottorati di ricerca

Componente UO

Emilio Hirsch

Dottorato di ricerca

Biomedical Sciences and Oncology

Coordinatore

Emilio Hirsch

Sede

Università di Torino