Loretta Tuosto

Associate Professor

loretta.tuosto@uniroma1.it

Academic Appointments

  • 1994-1996 Fellowship for the research on AIDS, by “Istituto Superiore di Sanità”, Molecular Immunology Unit Institut Pasteur, Paris France
  • 1996-1997 Fellowship by “Foundation pour la Recherche Medical” Molecular Immunology Unit Institut Pasteur, Paris France
  • 1997-1999 Fellowship by Istituto Pasteur- Fondazione Cenci Bolognetti, Dept. Cell. Biol. and Develop., Sapienza University of Rome
  • 1999-2004 Research contract, Dept. Cell. Biol. and Develop., Sapienza University of Rome
  • 2004-2012 Assistant Professor, Faculty of SMFN, Sapienza University of Rome
  • 2012-present Associate Professor of Immunology, Sapienza University of Rome
  • 20225 Call as Full Professor, Sapienza University of Rome

Honors and Awards

  • 1998 1st Prize PBI (GCI) for research activtity
  • 2000 1st Prize Mascia Brunelli, Associazione Italiana Colture Cellulari (ONLUS-AICC, 2000)
  • 2004-present Member of the Società Italiana d’Immunologia, Immunologia Clinica ed Allergologia (SIICA)
  • 2010-present Member of the European Association for Cancer Research (EACR)
  • 2016-present Associate Editor of Frontiers in Immunology, section “T cell Biology”
  • 2018-present F1000 Faculty member/H1 connect
  • 2020 Vigevani Research Project Prize 2020
  • 2022-present Associate Editor of Cells, MDPI Journals
  • 2024-present Associate Editor of Frontiers in Molecular Biosciences, section “Molecular Diagnostics and Therapeutics”

Scientific interests

Our research activity is focused in the fields of cellular and molecular immunology and oncology. In particular, we evidenced that the engagement of CD28 costimulatory molecule activates in primary T lymphocytes a non-canonical NF-κB2-like cascade leading to the selective recruitment of RelA/p52 and RelA/RelA dimers on the promoter of several NF-κB target genes including survival and inflammatory genes. We also characterized the role of CD28 in the regulation of the metabolic and inflammatory processes in Multiple Sclerosis (MS), highlighting an important contribution of class 1A PI3K associated with CD28 in the reprogramming of the metabolic processes that maintain/amplify the inflammatory phenotype of peripheral T lymphocytes.

Actually, we are working on the characterization of the role of CD28 in the inflammatory response to bacterial superantigens and on novel immunotherapeutic strategies for ovarian cancer.

Contribution to Science

Our research activity has been focused at characterizing the role of p53 and p73 oncosuppressors in the acquisition of resistance to apoptosis by tumour cells. These studies contributed to the identification of a new tumour-associated mutant of p53 (K351N) involved in the acquisition of resistance to apoptosis in ovarian cancer.

We also contributed at characterizing the mechanisms and molecules regulating the inflammatory signals elicited by human CD28 costimulatory molecule in primary T lymphocytes. We were among the first to identify at a cellular and molecular level of distinct signalling abilities between human and mouse CD28, thus emphasizing the essential need to pay attention to molecular details when transferring results from preclinical models to the bedside.

We also clarify the pivotal role of membrane phospholipid kinases (PIP5K, PIP4K and class 1A PI3K), in the regulation of the TCR and CD28 downstream signaling functions in T lymphocytes.

5 Selected publications

  • Porciello N, Grazioli P, Campese AF, Kunkl M, Caristi S, Mastrogiovanni M, Muscolini M, Spadaro F, Favre C, Nunès JA, Borroto A, Alarcon B, Screpanti I, Tuosto L. A non-conserved amino acid variant regulates differential signalling between human and mouse CD28. Nat Commun. 2018 Mar 14;9(1):1080. doi: 10.1038/s41467-018-03385-8.
  • Tuosto L, Capuano C, Muscolini M, Santoni A, Galandrini R. The multifaceted role of PIP2 in leukocyte biology. Cell Mol Life Sci. 2015 Dec;72(23):4461-74. doi: 10.1007/s00018-015-2013-0.
  • Cianfrocca R, Muscolini M, Marzano V, Annibaldi A, Marinari B, Levrero M, Costanzo A, Tuosto L. RelA/NF-kappaB recruitment on the bax gene promoter antagonizes p73-dependent apoptosis in costimulated T cells. Cell Death Differ. 2008 Feb;15(2):354-63. doi: 10.1038/sj.cdd.4402264.
  • Tavano R, Contento RL, Baranda SJ, Soligo M, Tuosto L, Manes S, Viola A. CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapse. Nat Cell Biol. 2006 Nov;8(11):1270-6. doi: 10.1038/ncb1492.
  • Marinari B, Costanzo A, Marzano V, Piccolella E, Tuosto L. CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappaB subunits on IL-8 and Bcl-xL gene promoters. Proc Natl Acad Sci USA. 2004 Apr 20;101(16):6098-103. doi: 10.1073/pnas.0308688101.

On-going Grants

Project Title Funding source Amount (Euros) Period Role of the PI
Improving ovarian cancer immunotherapy by the combination of Discoidin Domain Receptor 2 blockade and bispecific antibodies targeting CD28 and tumour-associated antigens PRIN 2022 PNRR 92.035 01.12.2023-30.11.2025 PI (30% of time)
Dissecting how microenvironment remodelled by tumor and stromal cells facilitate ovarian cancer metastasis: interaction between integrins and microbiome PRIN 2022 54.375 04.02.2025-03.02.2027 PI (20% of time)

Complete list of published work in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/loretta.tuosto.1/bibliography/public/

 KEYWORDS:

T cells; CD28; Inflammation; Multiple Sclerosis; Staphylococcal superantigens; Cancer immunotherapy.

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