Research areas and methodologies

Scopes

  • Translational medicine
  • Search for biomarkers and new molecular targets in breast cancer, mesothelioma, colorectal neoplasms, lymphomas and acute myeloid leukemia
  • Pathology and molecular genetics of complex diseases and cancer
  • Personalized Medicine: complex diseases and tumors.

Methodology

  • Modeling of primary and metastatic solid tumors using organoids: We have developed methods to grow human cell lines and human samples under non-adherent conditions, such as spheroids. We have since shown that this condition enriches for cells with progenitor and chemoresistant characteristics and that this setup is suitable for screening of clinically relevant drugs. We can associate the growth of spheroids and organoids from primary samples to the analysis of the distribution of cell subpopulations during adaptive stress. This allowed us to isolate cell subpopulations with specific skills towards stemness, chemoresistance and metastasis. We also exploited natural compounds and clinical-grade TKIs to attenuate this protumorigenic remodeling of cell subpopulations and explored their mechanism of action.
    More recently, we have transferred this knowledge to organoids. We can obtain organoids from primary tumors, from metastatic material (synchronous and asynchronous) and from unaffected host organ tissue. We have developed specific protocols to expand metastatic material, based on the concept of "tissue mimicry". We are able to propagate organoids with high fidelity to the source sample in terms of marker and gene expression. We can run one screening pharmacological in silico (drug repurposing) to identify FDA/EMA-approved compounds capable of attenuating the formation and/or growth of organoids, potentially suitable for testing in adjuvant contexts. We are currently focused on colorectal cancer, breast cancer (metastatic) and mesothelioma.
  • Study of intra- and inter-tumor heterogeneity (ITH), through different -omics (genomics, transcriptomics, epigenomics, metabolomics) and different technologies, including single-cell-analysis, aimed at Personalized Medicine, both for the development of targeted drugs (through specific molecular targets), and for the definition of predictive biomarkers of response to therapy and/or prognostic biomarkers, with the aim of developing specific panels of markers for the classification and personalized treatment of cancer for the singol patient. These technologies are applied both to the solid tumors already mentioned, and to leukemias (AML – acute myeloid leukemia), and to lymphomas (B-cell lymphoma). We have recently used metabolomics and, more specifically, lipidomics approaches to investigate the lipid profile of Patient-Derived-Tumor-Organoids (PDO and PDTO) by mass spectrometry. These new approaches could allow the identification of new therapeutic targets and biomarkers of prognostic stratification in cancer.
  • Study of "complex" and "complicated" "models" of disease pathogenesis, integrating the notions on the epigenetic control of the stem compartment and the programming and control of lineage commitment, with the system of signaling between cells and tissues, in the integration of the organism and interaction with the internal and external environment, according to the so-called "One health".

Patents

  • DNA Vaccines Expressing Hypervariable VH-CDR3 Idiotypic Determinants. FAZIO, Vito Michele; SAGLIO, Giuseppe. US 2004109849A1, issued: US 7,354,759 (B2) April 8, 2008; DE60124313 T2; WO2002/055559A1; EP 1355946 A1; PCT/IT2001/000014 
  • Anti-Tumoral Immunogenic Peptides and Vaccine Thereof. FAZIO, Vito Michele; GARACI Enrico; RINALDI Monica; SINIBALDI, Paola. US 2009232837A1, issued: US 9,150,627 (B2) October 6, 2015; WO2006070432 (B1)
  • Immunogenic Peptides, Nucleic Acids Encoding the Same and Use thereof in Cancer Treatment and Diagnosis. FAZIO, Vito Michele; FOX, Gisella; SAGLIO, Giuseppe. (WO/2006/008078 A1; PCT/EP2005/007709; US 20080107662 A1; EP1769076A1).

Collaborations with other Research Centers

  • IRCCS Hospital Home for the Relief of Suffering
  • National Cancer Institute “Regina Elena” IFO
  • CNR-Institute of Translational Pharmacology. Rome, L'Aquila, Cagliari, Palermo.
  • University of Naples “G. Vanvitelli”
  • LUM University; “De Gennaro” Bari
  • University of Rome “Roma Tre”
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, 20892, USA.
  • Cancer Research institute, University College of London
  • Center for Haematology, Imperial College of London
  • Barts Cancer Institute, Queen Mary University of London