Scientific background:

The research activity of the Developmental Biology laboratory team, coordinated by Prof. Geppino Falco, is focused on understanding the molecular mechanisms that regulate self-renewal and differentiation of stem cells. Stem cells are responsible for embryonic development, postnatal growth and tissue regeneration in adult organisms by proliferation and differentiation. Similarly, cancer stem cells, present within tumors, share the same characteristics as stem cells and are therefore responsible for the growth of the tumor itself. The main interest of the laboratory is to identify molecular targets capable of inducing differentiation of gastric cancer stem cells. The goal is to improve, through "precision medicine", diagnosis and therapy of cancers associated with the gastric tract.

The projects currently active are carried out in close collaboration with the team of the Stem Cell Biology laboratory located at the Biology Department of the University of Naples "Federico II" and with the team of the Cancerogenesis and Preclinical Models laboratory located at IRCCS - CROB.

Research lines:

Epigenetics and Energy Metabolism of stem cells

This research line aims at investigating the energetic mechanisms that characterize the metabolism of stem cells in order to identify and characterize new molecular targets for cancer therapies. The hypothesis is based on evidence that demonstrates how the molecular and epigenetic mechanisms implemented by stem cells can be preserved in cancer stem cells. Our recent studies have shown how the Zscan4 gene, in addition to regulating the genomic stability of stem cells, adds resistance to the differentiation stimuli of retinoids with strong implications in cancer biology.

Role of calcium channels in the apoptotic resistance of gastric cancer cells: identification of presumed molecular targets.

The calcium ion present inside the cell is stored in specific compartments and its cytosolic concentration is finely regulated. In the presence of stimulation, calcium ions diffuse into the cytoplasm to activate intracellular signaling mechanisms. A possible role for intracellular Ca2 + imbalance in neoplastic disease has been demonstrated in several cancers such as breast cancer; on the contrary, little is known about this alteration in gastric cancer. This line of research hypothesizes that a possible mechanism responsible for resistance to apoptosis in gastric cancer could be mediated by molecular alterations that compromise the homeostasis of intracellular ionic calcium, affecting the progression of the disease. The goal is to identify a molecular target associated with calcium metabolism capable of restoring sensitivity to apoptosis, providing the molecular basis for setting up therapeutic programs to reduce drug resistance.

Comparison of adjacent tissue and tumor tissue

Gastric cancer (GC) is a leading cause of cancer-related death. Molecular heterogeneity is a determinant of clinical outcomes and currently lacks an exhaustive classification. Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies. However, this tissue has unique characteristics that differentiate it from both tumor tissue and proper healthy tissue. The present research line aims to characterize the NAT transcriptome to improve the understanding of the molecular alterations typical of gastric cancer.

Role of cellular heterogeneity and self-renewal capacity in the chemo-resistance of gastric cancer

This line of research aims at identifying new markers of gastric cancer stem cells to be used as potential therapeutic targets in gastric cancer. Based on this scenario, the development and standardization of pre-clinical study models, such as organoids, has been proposed. This in vitro culture is derived from stem cells capable of self-organizing in order to mimic the architecture, function and molecular signature of the tissue of origin. The strong similarity with the primary samples of the cancer patient makes organoids an optimal pre-clinical model by reducing development times, shorter than xenografts, and allowing the verification of molecular hypotheses through gene manipulation.