Alessio Paone


Titolo Pubblicato in Anno
Anticancer activity of (S)-5-Chloro-3-((3,5-dimethylphenyl)sulfonyl)-N-(1-oxo-1-((pyridin-4-ylmethyl)amino)propan-2-yl)-1H-indole-2-carboxamide (RS4690), a new dishevelled 1 inhibitor CANCERS 2022
A conserved scaffold with heterogeneous metal ion binding site: the multifaceted example of HD-GYP proteins COORDINATION CHEMISTRY REVIEWS 2022
Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex THE FEBS JOURNAL 2022
Nutrient sensing and biofilm modulation: the example of L-arginine in Pseudomonas INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 2022
Inhibition of Glycolysis Impairs Retinoic Acid-Inducible Gene I-Mediated Antiviral Responses in Primary Human Dendritic Cells FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY 2022
Extracellular serine empowers epidermal proliferation and psoriasis-like symptoms SCIENCE ADVANCES 2022
Studying ggdef domain in the act: Minimize conformational frustration to prevent artefacts LIFE 2021
High-fat diet leads to reduced protein o-glcnacylation and mitochondrial defects promoting the development of alzheimer’s disease signatures INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 2021
Biophysical characterization of melanoma cell phenotype markers during metastatic progression EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS 2021
Modelling of SHMT1 riboregulation predicts dynamic changes of serine and glycine levels across cellular compartments COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL 2021
Importance of amino acids in brain parenchyma invasion by cancer cells ONCOSCIENCE 2021
Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex 16th SIBBM Seminar Frontiers in Molecular Biology Frontiers in metabolic research Abstracts 2021
Structural clues of Serine hidroxymethyltransferase (SHMT) riboregulation 2nd Italian Crystallographic Association Biological MacroMolecules Group Meeting 2021
The emerging role of amino acids of the brain microenvironment in the process of metastasis formation CANCERS 2021
Metformin is a pyridoxal-5′-phosphate (PLP)-competitive inhibitor of SHMT2 CANCERS 2021
Targeting the interaction between the SH3 domain of Grb2 and Gab2 CELLS 2020
Cytosolic serine hydroxymethyltransferase controls lung adenocarcinoma cells migratory ability by modulating AMP kinase activity CELL DEATH & DISEASE 2020
Structure and function of HD-GYP phosphodiesterases Microbial Cyclic Di-Nucleotide Signaling 2020
The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism NUCLEIC ACIDS RESEARCH 2019
Linking infection and prostate cancer progression: Toll-like receptor3 stimulation rewires glucose metabolism in prostate cells ANTICANCER RESEARCH 2019


  • LS1_2
  • LS4_9
  • LS4_12


  • Life-science technologies & biotechnologies

Interessi di ricerca

From the beginning, Alessio Paone's research activity has been
focused on the study of the function of proteins involved in tumor
processes and their role in cellular metabolic re-programming, with
an approach that ranges from the biochemistry of macromolecules and
their interactors, to molecular and cellular biology. Currently, he is
also directly involved in managing the experimental set up of the
One Carbon Metabolism
Cancer cells
HypACB facility at the Department of Biochemical Sciences in
Sapienza, whose service is to gain quantitative respiratory/energetic
parameters of cellular in normoxia and under hypoxic conditions.
More in detail, his research work spna from two main topics:
1) Mechanism of re-shaping of One carbon Metabolism in
In the last six years, his work has been focused on proteins involved
in cellular serine/glycine-one-carbon-SGOC metabolism as important
factor in tumor transformation; his study is mainly (but not only)
focused on lung cancer. He is involved in the characterization of the
mechanism behind the SGOC metabolic re-programming, in order to
identify the metabolic status (and vulnerability) of lung cancer cells
required to sustain proliferation. In particular, the role of the enzyme
serine hydroxylmethyltransferase (SHMT), which strongly supports
the production of key molecules for tumor proliferation such as DNA
bases or methyl group donors, has been analyzing by integrating
protein biochemistry and engineering with cell biology.
Main achievement of his research:
- Explaining specific role of the cytosolic SHMT in supporting
the thymine incorporation during DNA replication in lung cancer
- Characterizing novel role of SHMT as moonlight enzyme. He
contributed in showing that SHMTs are able to interact with high
affinity with RNA; these interactions is required to control both the
expression of the different isoforms of the enzyme and catalysis.
- Identification of novel strategies to target SHMT. Beyond the
physiological relevance of the RNA/SHMT interactions, this feature
allowed the design of novel tool to inhibit the enzymatic activity of
SHMTs. A draft of a patent is currently under evaluation of the
Academic committee.
- Connection between the inflammatory mechanisms regulated
by the TLRs and the metabolic alterations in the tumor cells.
2) "Toll Like Receptors" (TLR) in cancer cells.
During the first post-DOC period, the research focus has been on a
group of proteins called "Toll Like Receptors" (TLR) and their role in
cancer cells. TLRs are receptors of innate immunity and represent the
first line of defense against pathogen invasion. He contributed in
unveiling the mechanism of TLR activation and of the associated
signal transduction process upon interaction of these proteins with
specific ligands in tumor cells.
Main achievement of his research:
- it has been shown that the activation of these receptors can induce
diametrically opposed effects on tumor cells from different tissues
causing in some cases apoptosis, in others proliferation, angiogenesis
- identification of novel endogenous ligands for TLR7 / 8 with protumor functions. In a work published in PNAS in 2012 a new family
of ligands for hTLR8 and mTLR7 receptors was discovered,
including several mature microRNAs, secreted by tumor cells. These
molecules were able to activate these receptors expressed on the cells 
of the immune system inducing a rewiring in the secretoma which in
turn support the growth of metastases in the lung.
The results reported were also obtained thanks to the skills acquired
by Alessio Paone specifically in the study of:
- protein-protein and protein-RNA interactions;
- signal transduction;
- processes of cell death;
- regulatory metabolic mechanisms.
By taking advantage of his technical expertise in:
-protein biochemistry and engineering: expression and purification of
-cell biology: cell culture, Western Blotting, RT-PCR, iRNA,
fluorescence microscopy, respiratory assays through Seahorse
-in vivo: mouse handling, intraperitoneal injections, xenograft tumor
inoculation, in vivo angiogenetic assays.
-data handling: standard statistics, seahorse data analysis


cancer metabolism
amino acids
cancer metastasis
RNA-protein interactions
tumor microenvironment
blood brain barrier

Gruppi di ricerca

Gruppi di ricerca - Responsabile

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