Research
Mutations of tyrosine kinase receptors
We have developed and applied a bioinformatic tool to analyze pan-cancer missense mutations at the protein domain level. This approach allows to pinpoint novel rare cancer-associated variants and to highlight their correspondence with well-known mutations. We are characterizing the role of various mutations of the tyrosine kinase domain of tyrosine kinase receptors in cancer progression and response to therapies. Our studies could help to predict the inter-individual differences in terms of prognosis and response to drugs, improving the application of precision oncology. Reed references Biochim Biophys Acta Rev Cancer. 2021 Dec;1876(2):188614. doi: 10.1016/j.bbcan.2021.188614;Cancer Lett. 2021 Jan 1;496:84-92. doi: 10.1016/j.canlet.2020.09.027; Cancer Lett. 2021 Jun 1;507:80-88. doi: 10.1016/j.canlet.2021.03.007; Cells. 2024 Aug 13;13(16):1346. doi: 10.3390/cells13161346; Neoplasia. 2025 Sep;67:101195. doi: 10.1016/j.neo.2025.101195.
Obesogenic behavior and climate change
We have recently started a new research project focused on understanding how metabolic features and lifestyle of obese individuals affect adverse climate change. In collaboration with Discovery foundation (Greece) company, we are investigating how obesogenic behaviors, including the consequent metabolic adaptations, can contribute to altering the environment. Our studies will likely pinpoint novel strategies to preserve our world.
Aberrant VEGFR2 supports tumor growth by extracellular matrix remodeling
The extracellular matrix (ECM) is a dynamic and multifunctional component of the tumor microenvironment and is increasingly recognized as a key driver of cancer cell aggressiveness. Beyond providing structural support, the ECM regulates cell adhesion, migration, proliferation, and survival through biochemical and mechanical cues. While extensive ECM remodeling during tumor growth is known to promote invasion, metabolic reprogramming, and therapy resistance, how tumor-derived ECM mechanically influences angiogenesis, tumor growth, and dissemination remains less well understood.
This project is based on the concept that ECM alterations are not merely a consequence of cancer progression, but active regulators of tumor and stromal cell behavior. We aim to investigate how aberrant activation of the receptor tyrosine kinase VEGFR2 promotes pathological ECM remodeling in melanoma and ovarian cancer, and how these changes affect both tumor cells and endothelial cells. Using syngeneic and xenograft models, we will study how endothelial cells respond to tumor-associated ECM remodeling in vitro and in vivo, and how remodeled ECM modulates intracellular mechanotransduction pathways that, in turn, reprogram the metabolic behavior of both tumor and endothelial cells. These processes will be linked to VEGFR2-dependent signaling, including the PI3K-AKT and ERK pathways, which regulate the expression of genes involved in ECM structure and remodeling.
To address these questions, we will employ label-free and high-resolution fluorescence microscopy approaches to visualize the three-dimensional organization and remodeling of the ECM in vitro and in vivo. We will analyze how ECM changes affect intracellular mechano- and biochemical signal transduction, including mechanical forces at focal adhesion sites, reactive oxygen species production, calcium fluxes, and the diffusion of transmembrane proteins along the cell membrane. In addition, advanced techniques such as FRAP, FRET, and FLIM-FRET will be used to characterize protein–protein interactions and protein dynamics. Finally, we will evaluate whether pharmacological inhibition of VEGFR2, using tyrosine kinase inhibitors such as lenvatinib, can restore ECM organization and reprogram the tumor microenvironment, offering a potential strategy to limit tumor progression, angiogenesis, and metastatic dissemination.
Cell Death and Disease (2026) 17:169 ; https://doi.org/10.1038/s41419-025-08404-3
VEGFR2 in ovarian cancer
V
EGFR2, typically known for promoting tumor growth, can actually play an anti-tumoral role in certain cancers. Our research explores this surprising function in high-grade serous ovarian carcinoma (HGSOC), an aggressive and hard-to-treat form of ovarian cancer that often returns after therapy. Using both cellular and animal models, we investigate the biochemical and molecular mechanisms behind VEGFR2’s unexpected behavior.
One key focus of our study is how VEGFR2 regulates mechanotransduction—the way cells sense and respond to mechanical cues from their environment. VEGFR2 appears to help cells stay anchored by supporting structures called focal adhesions, which function like cellular “anchor points.” When VEGFR2 is silenced, these anchors weaken, their signaling becomes unstable, and the mechanical forces that keep cells in place are disrupted. As a result, cancer cells become more mobile and invasive, potentially accelerating tumor progression.
Membrane dynamics of receptor tyrosine kinases
Membrane dynamics have emerged as crucial determinants of the function of cell surface receptors. In our lab we are interested in investigating how the dynamics of surface receptors along the membrane are intertwined with their function. Using quantitative FLIM/FRET and FRAP imaging techniques, we study the membrane dynamics of tyrosine kinase receptors such as VEGFRs and FGFRs. Read references 2017, 2020 and 2024
.
Bio-scaffolds for the regeneration of brown adipose tissue
As the proportions of obesity increase worldwide, it becomes crucial to develop innovative and effective strategies to treat patients with obesity. The strategy we are pursuing consists in promoting adipose tissue health and browning through the implantation of bio-scaffolds. In this framework, angiogenesis plays a central role allowing for physiological adipose tissue expansion and preventing its dysfunction. In our lab we are studying novel natural bio-scaffolds that could support angiogenesis in beige adipose tissue.
Gremlin-1 in development, angiogenesis, cancer and metabolic disorders
Our group has contributed to the identification and characterization of Gremlin-1 as a pro-angiogenic ligand of VEGFR2. In our lab we are interested in studying the biochemical and molecular bases of gremlin-1 physio-pathological function. Considering the pathogenetic role of gremlin-1 in various human disorders, a better understanding of its function is of pivotal importance to design novel strategies to target gremlin-1 and its function in human pathologies. Read references 2007, 2008, 2010, 2012, 2015, 2016, 2023.
