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Donatella Valdembri is an Associate Faculty Member who works with Guido Serini to evaluate the literature relevant to their research interests. Her research interests are the cellular and molecular mechanisms by which endothelial cell polarity is established and maintained by means of endo-exocytic traffic and Golgi secretion.

Can you tell us about your research interests?

My research interests are mainly focused on the study of the mechanisms promoting blood vessel formation. Indeed, solid cancers depend on angiogenesis to grow and metastasize. However, tumour blood vessels are structurally and functionally abnormal since molecular pathways controlling vascular morphogenesis are altered in cancer. Angiogenesis relies on physical interactions among endothelial cells, lining the internal surface of blood vessels, and extracellular matrix proteins, such as fibronectin.

I like working on F1000Prime because it is a stimulating environment that helps to keep scientists updated on the most recent research advances.

The interaction between fibronectin and its major receptor α5β1 integrin is key to establish apico-basal endothelial cell polarity. In addition, cell adhesions continuously turn over through endo-exocytic circuits that allow dynamic fibronectin fibrillogenesis in angiogenic endothelial cells.

My current interest is the study of the signalling pathways originated at adhesive sites that, controlling the basolateral secretion of newly synthesized extracellular matrix proteins, leading to cell polarity onset. Defining the mechanisms of endothelial cell polarity onset may allow us to identify new targets for therapies aimed at normalizing tumour blood vessels, improving anti-cancer drug delivery, and inhibiting metastatic dissemination.

How did you get involved in your field of study?

I got involved in the field of angiogenesis and embryonic blood vessel development at the very beginning of my scientific career. During my PhD, I participated in a research study, which led to the discovery of class 3 semaphorins as guidance cues during blood vessel formation and I worked on the in vivo experiments on chicken embryos.

 A particularly inspiring encounter at the beginning of my career, was when I met the Italian Nobel Prize laureate in Physiology or Medicine; Rita Levi Montalcini when she held a magistral lecture at our institute.

I continued my research studying the semaphorin receptor Neuropilin 1 and I uncovered its role in supporting endothelial cell adhesion to fibronectin by promoting the vesicular traffic of active α5β1 integrin back and forth from cell adhesion contacts to the extracellular matrix. The active integrin traffic became my main interest and I moved on discovering that the presynaptic molecular adaptor PPFIA1, interacting with active α5β1 integrin, drove its recycling along with fibronectin secretion from the –trans-Golgi network. My current interest is the study of mechanisms regulating the onset of endothelial cell polarity exploiting the biosynthetic vesicular routes from the Golgi.

I realized how little we know about nature and what a wonderful gift it is to witness these hidden elements of life.

Where do you work?

I am a junior group leader at Candiolo Cancer Institute – FPO, IRCCS in Italy and I work in a small team together with two young and motivated scientists: Fabiana Clapero, who is now at the end of her PhD program and Dora Tortarolo, a PhD student. Our Institute is a private non-profit institution founded and supported by the Fondazione Piemontese per la Ricerca sul Cancro-Onlus (FPRC) and by the Fondazione del Piemonte per l’Oncologia (FPO). The Institute is a recognized IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) by the Italian Ministry of Health. Candiolo Cancer Institute works in synergy with the University of Torino Medical School and hosts research laboratories and oncological hospital, which are strictly interfaced.

Our Institute is endowed with a major computer, cell and molecular biology, protein biochemistry, gene transfer and expression equipment. Moreover, several BSL2 units and one BSL3 unit for cell cultures are present. We have some core facilities and services available to us: bioinformatics, DNA sequencing, DNA Microarray analysis, high content real-time PCR, FACS and cell sorting, animal facility and advanced fluorescence microscopy.

I am very fond of fluorescent microscopy because it gives me the opportunity to stand in front of an infinitesimal and silent universe made of subcellular organelles and molecules.

Regarding the latter, I am one of the scientists who is in charge of the facility, which currently is equipped with two laser confocal microscopes, a multi-dimensional workstation for live cell imaging in phase contrast, widefield fluorescence, FRET and TIRF, a laser confocal microscope with a gated 3D STED for high resolution and a fluorescence microscope endowed with a motorized system for High Content Screening.

How do you cope with the stresses of your work?

The most stressful moments in our job are the extremely busy periods in which we have many heterogeneous tasks to address at the same time or the last few weeks before a grant submission. Moreover, basic research is sometimes blamed because it has no immediate application in medicine and it is extremely competitive to obtain funding. Fortunately, in scientific research, there are particularly relaxing activities such as, observing samples under the microscope.

I am very fond of fluorescent microscopy because it gives me the opportunity to stand in front of an infinitesimal and silent universe made of subcellular organelles and molecules. In these moments, I realize how little we know about nature and what a wonderful gift it is to witness these hidden elements of life.

Another two important aspects that help me to overcome the daily stresses in my work are the thrill of every new discovery, brought to light by a well-designed experiment, and the challenge of the answering the most difficult questions in research, requiring fantasy and artistic creativity.

 Finally, I enjoy discussing science with a few colleagues at the end of the working day, especially with my mentor Guido Serini, for they are reassuring and valuable occurrences that take place when the lab is empty and only the most motivated remain.

What do you like about working on F1000Prime?

I like working on F1000Prime because it is a stimulating environment that helps to keep scientists updated on the most recent research advances. Moreover, F1000Prime encourages critical and constructive scientific discussion and the exchange of thoughts.

In scientific research, there are particularly relaxing activities such as, observing samples under the microscope.

My last recommendation was on the paper “Thrombospondin-3 augments injury-induced cardiomyopathy by intracellular integrin inhibition and sarcolemmal instability” by Ships and colleagues working in Molkentin’s lab. What has most attracted me to this work was the fact that some thrombospondins can form complexes with newly synthesized dystroglycans and integrin enhancing their Golgi to plasma membrane traffic. Thrombospondin 4 exerts its activity binding integrins via an RGD motif, while thrombospondin 3, which contains an EDG motif in the same molecular position, cannot interact with integrin and plays an opposite function.

This research highlighted the possibility that newly synthesized proteins may form functionally active complexes before being secreted to the cell surface. Moreover, thrombospondin could represent a potential pharmacological target for therapies in post-injury striated muscle repair.

Finally, I enjoyed going through previous papers by Molenkin’s group, which thoroughly traced the path of thrombospondin function in cardiovascular diseases and skeletal muscle dystrophy.