Translational Endocrinology and Metabolism Lab

Main research areas

Neuroendocrinology

Coordinator: Dr. Giampaolo Trivellin. The research line focuses on several key areas in the field of Medical Genetics and Endocrinology, primarily centered around the genetic and epigenetic mechanisms underlying pituitary tumors and related disorders. The team investigates genetic defects causing pituitary tumors, with an emphasis on gigantism and acromegaly. Research efforts are dedicated to understanding the transcriptional regulation and intracellular signaling of GPR101 gene, using transgenic zebrafish models and cell lines to elucidate the receptor’s role in growth regulation. The team aims to decode the epigenetic changes affecting GPR101 and other genes involved in pituitary tumorigenesis. This includes studying chromatin architecture disruptions and their impact on gene expression in human tumor tissues, and identifying regulatory sequences such as enhancers that are active in pituitary cells. Another major focus is on loss-of-function variants in the PAM gene, which are linked to pituitary hormone hypersecretion.

Bone biology

Coordinator: Dr. Cristina Sobacchi Our research deals with the molecular and cellular mechanisms involved in bone pathophysiology. For more than 20 years the main focus has been on a rare genetic skeletal disorder, called Osteopetrosis. Genetic studies in patients have been performed which substantially contributed to the dissection of the molecular basis of human Osteopetrosis. Studies in patients have been accompanied by preclinical studies aimed at the development of new therapies for osteopetrosis (particularly with respect to the RANKL-deficient form), by using pharmacological, cell-based and gene therapy approaches. Additional recent topics in the lab are Skeletal Stem Cell biology; the role of oxidative stress in diverse bone pathophysiological conditions, particularly focusing on the DPP3/Keap1/Nrf2 antioxidant pathway and related molecular and cellular events; bone matrix composition and properties in preclinical models of disease; and the mechanisms underlying bone infection (in collaboration with Dr Antonio Inforzato).

Oncological endocrinology

Coordinator: Dr. Eleonora Vitali. Neuroendocrine tumors (NETs), originating from cells in the diffuse neuroendocrine system, predominantly manifest in the gastrointestinal tract and lungs. Advanced NETs frequently resist conventional biotherapy or chemotherapy, necessitating novel therapeutic strategies. The mechanisms leading to NETs’ development, progression, and resistance to therapy are poorly understood and little is known about the impact of tumor microenvironment. We recently demonstrated the crucial role of NF-kB and STAT3 interplay in Pancreatic Neuroendocrine Tumor (Pa-NET) progression and resistance to Everolimus, suggesting the need for further investigation into the interplay between inflammatory pathways and NET cells. Moreover, we previously demonstrated that cytoskeleton actin-binding protein filamin A (FLNA) is an important player in regulating Pa-NETs’ biological behavior and is involved in Lung-NET aggressiveness. Our translational research aims to provide a deeper understanding of NET biology, identify novel targets for pharmacological intervention, and develop new therapeutic strategies to overcome drug resistance and suppress NET progression.