Dr. Alessandra Folci and Dr. Giampaolo Trivellin have won the Marie Skłodowska Curie Action-Individual Fellowship 2018 call, thanks to which they will pursue their research projects in Humanitas: Dr. Folci in the team of Professor Michela Matteoli, Director of the Neuro Center of Humanitas, and Dr. Trivellin in the team of Professor Andrea Lania, Head of the Laboratory of Cellular and Molecular Endocrinology and U.O. of Endocrinology and Diabetology.

“Physiological consequences of Protocadherin-10 sumoylation on neuronal function”, the title of the winning project presented by Alessandra Folci, while Dr. Giampaolo Trivellin won the call with the project “Identification and functional validation of novel enhancer sequences involved in pituitary gland development and pathology”.

With the help of the two researchers, we try to understand what they do in their research projects.

The project by Alessandra Folci

“The SUMO-PCDH10 project aims to study the role of a particular protein modification called SUMOilation on the functioning of the Pcdh10 protein in neurons. Pcdh10 is a protein that plays a key role in the central nervous system, whose mutations have been associated with the development of autism.

During my experience as a senior postdoc in the laboratory of Dr. Martin (IPMC, CNRS, France) I had the opportunity to study the role of SUMOilation on the functionality of neurons. In fact, in neurons, SUMOilation regulates many cellular processes including synapse maturation and synaptic plasticity (a fundamental mechanism underlying phenomena such as learning and memory). So I developed a personal interest in the role of SUMOilation in the development of diseases of the nervous system including autism and intellectual disability.

Thanks to this call, I will have the opportunity to carry out my research project in a team led by Professor Michela Matteoli; in particular, I will study the physiological and pathological consequences of Pcdh10 SUMOilation on the formation of synapses through sophisticated biochemical methods and advanced microscopy techniques.

In the last few years we have studied the role of SUMOilation on neuronal communication and we have discovered how an altered SUMOilation of key proteins of the central nervous system can lead to the development of serious diseases such as Parkinson’s, Alzheimer’s and autism. Therefore, the SUMO-PCDH10 project, by studying the effect that SUMOilation has on the activity of Pcdh10 and its possible involvement in the pathogenesis of autism, will provide possible new therapeutic targets for patients with mutations on Pcdh10,” explained Dr. Folci.

The project by Giampaolo Trivellin

“X-related acrogigantism (X-LAG) is a pituitary gigantism syndrome characterized by excessive body growth, a condition that occurs very early (<2 years) and that I have recently helped to identify and characterize. The pituitary gland is called the “master gland” because it regulates the functioning of all the other endocrine glands in the body by producing chemical messengers called hormones. The X-LAG disease is caused from the development of pituitary tumors that lead to an excessive secretion of growth hormone, and is associated with a genetic defect: the duplication of the GPR101 gene.

Although this new knowledge has led to an early diagnosis and a faster start of the therapies currently available, we still know little about the physiological role of the GPR101 gene and how it regulates human growth. To this end, it remains, for example, to be clarified how the expression of GPR101 is controlled in the pituitary gland and the main objective of my research project is to identify the molecular mechanisms that cause the marked expression of the GPR101 gene in pituitary tumours of children with X-related acrogigantism.

Also thanks to new techniques, I expect to generate the data to significantly broaden our understanding of the molecular pathogenesis of X-related acrogigantism. Establishing how the expression of the GPR101 gene is controlled is fundamental in order to be able to develop therapeutic agents that control the amount of GPR101 protein produced in pituitary tumors in patients with X-LAG. Further aspects of my research project could represent an important step forward to better understand the development, function, and oncogenetic processes typical of pituitary cells. Understanding all these aspects will therefore benefit not only patients with X-LAG but also other patients with growth disorders and/or other pituitary diseases,” concluded Dr. Trivellin.