Parolini Silvia


Responsabile dell'U.O.

Cognome e Nome

Parolini Silvia

Qualifica

PO

Dipartimento

Medicina Molecolare e Traslazionale (DMMT)

Settore scientifico disciplinare

BIO/17

E-mail

parolini@med.unibs.it

Telefono

030-3717724

Personale strutturato

Cognome e Nome

Tabellini Giovanna

Qualifica

PA

Dipartimento

Medicina Molecolare e Traslazionale (DMMT)

Ente di appartenenza

Università degli studi di Brescia

Cognome e Nome

Coltrini Daniela

Qualifica

PA

Dipartimento

Medicina Molecolare e Traslazionale (DMMT)

Ente di appartenenza

Università degli studi di Brescia

Cognome e Nome

Rezzola Sara

Qualifica

RTDB

Dipartimento

Medicina Molecolare e Traslazionale (DMMT)

Ente di appartenenza

Università degli studi di Brescia

Personale non strutturato

Cognome e Nome

Mutti Greta

Qualifica

Assegnista

Dipartimento

Medicina Molecolare e Traslazionale (DMMT)

Ente di appartenenza

Università degli studi di Brescia

Cognome e Nome

Loda Alessandra

Qualifica

Ph.D student

Dipartimento

Medicina Molecolare e Traslazionale (DMMT)

Ente di appartenenza

Università degli studi di Brescia

Linee di ricerca

Human Natural Killer cells (NK) were originally identified on the capability of killing certain tumor cell lines in the absence of deliberate previous stimulation. Recently, a novel concept has emerged indicating that the actual role of NK cells is not only confined to the destruction of virus-infected cells or tumors. This is particularly relevant during the early phases of acute inflammation, secondary to infection. Various studies were focused on the crosstalk between NK cells and monocyte-derived dendritic cells and more recently on the involvement of plasmocytoid dendritic cells, mast cells, basophils, eosinophils, and neutrophils. This is in accord with the fact that NK cells from blood can be attracted to peripheral tissues by several chemokines released during inflammatory responses. In contrast, a minority of NK cells from blood expresses receptors for homing to lymphoid tissues. In particular, the function of NK cells is regulated by a balance between opposite signals delivered by a set of HLA class I specific inhibitory receptors and by a number of activating receptors and co-receptors responsible for NK cell triggering. By the combined use of these receptors, NK cells can discriminate between normal HLA class I+ cells and cells that have lost the expression of HLA class I molecules as a consequence of tumor transformation or viral infection. For over a decade, our research group has been studying NK cells identifying novel functional molecules expressed on different subsets of NK cells and investigating NK cells derived from patients affected by primary immune deficiencies. Recently, in our laboratory, we also analyze the expression pattern and the function of inhibitory and activating NK receptors on different NK subsets derived from patients with epithelial ovarian carcinoma subjected to primary surgery. To better understand NK-mediated lysis mechanisms, a special attention was paid on the interaction between inhibitory/activating NK receptors and HLA class I molecules/tumoral ligands. Indeed, this may reflect a differential involvement of these receptors in controlling the process of tumor growth. These immunological analyses are possible thanks to the isolation in our laboratory of monoclonal antibodies that can be applied in these specific experiments where most commercially available reagents can not be used. At last, by generating monoclonal antibodies, our research group have identified novel NK cell receptors and markers that allowed a further characterization of different human NK cell subsets.

Tecnologie in uso dall'UO

  1. 1.
    NK cells culture technique and NK cell cloning
  2. 2.
    Primary cultures and cell line cultures
  3. 3.
    Immunocyto- and histochemistry
  4. 4.
    Generation and isolation of hybridomas producing monoclonal antibodies
  5. 5.
    NK cytotoxic functional assay and cytokine production tests
  6. 6.
    Western-blotting analysis
  7. 7.
    Immunofluorescence analysis by flow cytometry
  8. 8.
    Confocal microscopy
  9. 9.
    Basic molecular biology
  10. 10.
    Real-Time PCR

Strumentazione

Denominazione

ViiA7 Real-time PCR System
Axio Observer Zeiss
Confocale due fotoni Zeiss LSM 880
FacsCanto BD
BD FACS Aria TM IIIu cell sorter

Struttura ove la strumentazione è allocata

DMMT
DMMT
DMMT
DMMT
DMMT

Responsabile

Prof. Coltrini Daniela
Prof. Stefania Mitola
Prof. Stefania Mitola
Prof. Tabellini Giovanna
Dott.ssa Valentina Salvi

Pubblicazioni

  1. 1.
    CARD11 dominant negative mutation leads to altered human Natural Killer cell homeostasis. Baronio M, Gazzurelli L, Rezzola S, Rossi S, Tessarin G, Marinoni M, Damiano AS, Fiore M, Moratto D, Chiarini M, Badolato R, Parolini S, Tabellini G, Lougaris V.Immunobiology. 2023 Apr 5;228(3):152381. doi: 10.1016/j.imbio.2023.152381. Online ahead of print. PMID: 37086690
  2. 2.
    Hyperactive Akt1 Signaling Increases Tumor Progression and DNA Repair in Embryonal Rhabdomyosarcoma RD Line and Confers Susceptibility to Glycolysis and Mevalonate Pathway Inhibitors. Codenotti S, Zizioli D, Mignani L, Rezzola S, Tabellini G, Parolini S, Giacomini A, Asperti M, Poli M, Mandracchia D, Vezzoli M, Bernardi S, Russo D, Mitola S, Monti E, Triggiani L, Tomasini D, Gastaldello S, Cassandri M, Rota R, Marampon F, Fanzani A. Cells. 2022 Sep 14;11(18):2859. doi: 10.3390/cells11182859. PMID: 36139434
  3. 3.
    Lack of DOCK8 impairs the primary biologic functions of human NK cells and abrogates CCR7 surface expression in a WASP-independent manner. 4 Patrizi O, Baronio M, Gazzurelli L, Rossi S, Rezzola S, Marcenaro E, Plebani A, Badolato R, Parolini S, Lougaris V, Tabellini G. Clin Immunol. 2022 Apr;237:108974. doi: 10.1016/j.clim.2022.108974. Epub 2022 Mar 10.PMID: 35278713
  4. 4.
    Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋𝛋B kinase alpha (IKKα). Bainter W, Lougaris V, Wallace JG, Badran Y, Hoyos-Bachiloglu R, Peters Z, Wilkie H, Das M, Janssen E, Beano A, Farhat KB, Kam C, Bercich L, Incardona P, Villanacci V, Bondioni MP, Meini A, Baronio M, Abarzua P, Parolini S, Tabellini G, Maio S, Schmidt B, Goldsmith JD, Murphy G, Hollander G, Plebani A, Chou J, Geha RS. Sci Immunol. 2021 Sep 17;6(63):eabf6723. doi: 10.1126/sciimmunol.abf6723. Epub 2021 Sep 17. PMID: 34533979
  5. 5.
    Natural killer cell impairment in ovarian clear cell carcinoma. Patrizi O, Rampinelli F, Coltrini D, Pesce S, Carlomagno S, Sivori S, Pascale A, Marcenaro E, Parolini S, Tabellini G. J Leukoc Biol. 2020 Oct;108(4):1425-1434. doi: 10.1002/JLB.5MA0720-295R. Epub 2020 Aug 13. PMID: 32794325
  6. 6.
    The RAC2-PI3K axis regulates human NK cell maturation and function. Tabellini G, Baronio M, Patrizi O, Benevenuto A, Gazzurelli L, Plebani A, Parolini S, Lougaris V. Clin Immunol. 2019 Nov;208:108257. doi: 10.1016/j.clim.2019.108257. Epub 2019 Sep 3. PMID: 31491520
  7. 7.
    From Natural Killer Cell Receptor Discovery to Characterization of Natural Killer Cell Defects in Primary Immunodeficiencies. Tabellini G, Patrizi O, Dobbs K, Lougaris V, Baronio M, Coltrini D, Plebani A, Badolato R, Notarangelo LD, Parolini S. Front Immunol. 2019 Jul 24;10:1757. doi: 10.3389/fimmu.2019.01757. eCollection 2019. PMID: 31396241. Review.
  8. 8.
    Strengthening the AntiTumor NK Cell Function for the Treatment of Ovarian Cancer. Greppi M, Tabellini G, Patrizi O, Candiani S, Decensi A, Parolini S, Sivori S, Pesce S, Paleari L, Marcenaro E.Int J Mol Sci. 2019 Feb 19;20(4):890. doi: 10.3390/ijms20040890.PMID: 30791364 Free PMC article. Review.
  9. 9.
    A monoallelic activating mutation in RAC2 resulting in a combined immunodeficiency. Lougaris V, Chou J, Beano A, Wallace JG, Baronio M, Gazzurelli L, Lorenzini T, Moratto D, Tabellini G, Parolini S, Seleman M, Stafstrom K, Xu H, Harris C, Geha RS, Plebani A. J Allergy Clin Immunol. 2019 Apr;143(4):1649-1653.e3. doi: 10.1016/j.jaci.2019.01.001. Epub 2019 Jan 14. PMID: 30654050
  10. 10.
    CTLA-4 regulates human Natural Killer cell effector functions. Lougaris V, Tabellini G, Baronio M, Patrizi O, Gazzurelli L, Mitsuiki N, Pozzi MR, Grimbacher B, Parolini S, Plebani A. Clin Immunol. 2018 Sep;194:43-45. doi: 10.1016/j.clim.2018.06.010. Epub 2018 Jun 30. PMID: 29966715

Dottorati di ricerca

Componente UO

Parolini Silvia
Tabellini Giovanna
Rezzola Sara

Dottorato di ricerca

Genetica molecolare, Biotecnologie e Medicina Sperimentale
Genetica molecolare, Biotecnologie e Medicina Sperimentale
Genetica molecolare, Biotecnologie e Medicina Sperimentale

Coordinatore

Prof. Eugenio Monti
Prof. Eugenio Monti
Prof. Eugenio Monti

Sede

Brescia
Brescia
Brescia