General interests and key questions. We study how cells sense their environment and use this information to build and maintain tissues with specific form, size and function. We are also interested in how disruption of these homeostatic mechanisms leads to tumor formation, progression and metastasis, hoping to identify new routes for the treatment of incurable cancers. Specifically, our research focuses in three areas: (1) Mechanotransduction. Tissue architecture, mechanical forces and cell shape are overarching, yet poorly understood regulators of cell behavior. Key elements of these signals are cell-extracellular matrix (ECM) and cell-cell adhesions, cell polarity and the mechanical-induced distortion of the cytoskeleton that keep individual cells and whole tissues in a certain shape. Our work has shown that YAP and TAZ, two related transcriptional co-activators, are central elements by which, in living systems, form dictates biological function. Indeed, YAP/TAZ are readers of "structural" signals and mediators of their effects. A central goal in our laboratory is to uncover the nature of cellular mechanotransduction systems in normal and pathologic contexts. (2) Molecular attributes of cancer stem cells. We showed that TAZ is a molecular determinant of "cancer cell stemness". TAZ drives self-renewal and tumor initiation of cancer cells and TAZ is activated by epithelial-mesenchymal transition (EMT). We outlined a pathway by which loss of apico-basal polarity (an early step in EMT, and a hallmark of cancer) leads to TAZ stabilization through regulation of the Hippo pathway. We are now focusing on the TAZ and YAP targets that are causal for the cancer stem cell phenomenon. (3) Growth factor signaling. We investigate embryonic development to learn general principles, and identify new genes, by which growth factors (such as TGFß, FGF or Wnt ligands) collectively regulate tissue patterning and cell fate decisions. We are interested to apply these knowledge to elucidate how these contextual signals also regulate stem cell biology in adults, and act as elements of the tumor microenvironment essential to maintain cancer stem cells as well as the tumor's complex and "organ-like" cellular organization/hierarchy. Our approach to these goals entails both hypothesis-driven and data-driven investigations and combines an interdisciplinary set of expertise, ranging from molecular, biochemical and cell biological tools to animal models, tissue engineering, material science and "omic" approaches.
Department of Molecular Medicine
University of Padua
School of Medicine
viale Colombo 3
Web Page: http://www.bio.unipd.it/piccolo/