Dr Giovanna Zambruno works at Bambino Gesù Children’s Hospital in Rome, Italy on recessive dystrophic epidermolysis bullosa (RDEB). Some RDEB symptoms can be caused by skin cells making more scar tissue (fibrosis) than expected because the usual controls that prevent this are broken. This work is to understand some of those control mechanisms to see if they could be targeted by future treatments that could reduce the symptoms in RDEB that are due to scarring.  


Grant Title: MicroRNAs in dystrophic epidermolysis bullosa fibrosis: expression profiling, activity and therapeutic perspectives

Investigators: Dr Giovanna Zambruno, Consultant, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

Co-investigators: Dr Teresa Odorisio, Laboratory of Molecular and Cell Biology, IDI-IRCCS, Rome, Italy

Collaborator: Professor Leena Bruckner-Tuderman, Universitätsklinikum Freiburg – Hautklinik, Germany

Institution: Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, Rome, Italy                          

Start Date: 01/03/20 (for 3 years)

Grant amount: €196,500.00 (49% funding with DEBRA Austria)

Research type: Chronic inflammation and fibrosis Identification of drug targets


Our DNA is made-up of genes that store the information to build proteins that form our body. The DNA instructions are transcribed into RNA molecules called messenger RNAs (mRNAs), which serve to produce these proteins (translation). However, some RNAs, called non-coding RNAs, are not translated into proteins but regulate the amount of proteins produced. MicroRNAs (miRNAs) are non-coding RNAs that block protein production by interacting with specific mRNAs. MiRNAs are key regulators of all biological processes and their abnormal function contributes to many diseases, including fibrotic (scarring) skin disorders.

In recessive dystrophic epidermolysis bullosa (RDEB) unremitting blistering leads to severe fibrosis that plays an important role in the development of the most severe disease complications. Our group has observed that some miRNAs are more abundant in fibroblasts from RDEB patients (RDEBFs) and exert a pro-fibrotic activity in vitro. Based on these preliminary studies, the present project aims at identifying additional miRNAs dysregulated in RDEBFs and at characterizing their role in key fibrotic processes such as the production and release of important pro-fibrotic molecules (e.g. the transforming growth factor-b1) and the dermal (skin) stiffening. This study will contribute to expand knowledge about disease pathomechanisms and to identify novel miRNAs and miRNA targets as potential targets for innovative therapies to limit fibrosis.

About this research and why it is important: 

“Injury- and inflammation-driven fibrosis is a constant and progressive feature in RDEB. It is responsible for severe and invalidating clinical manifestations such as pseudosyndactyly (mitten hand formation), limb contractures and mucosal strictures, and is implicated in the development of early and aggressive skin squamous cell carcinoma. Counteracting fibrosis represents a strategy to improve disease course and patients’ quality of life. Recently, significant efforts of the EB scientific community have been devoted to decipher the molecular bases of RDEB-associated fibrosis. However, the fibrogenic mechanisms are intricate and quite diversified even in patients carrying the same genetic background. Epigenetics embraces a number of regulatory events standing above the fundamental genetics-based “DNA instructions” and involved in shaping health and disease conditions in a pervasive mode. Our investigations will contribute to expand knowledge about the miRNA-mediated epigenetic events underlying the fibrotic behaviour of patients’ cells. For the first time, our analyses will investigate the expression levels of a large number of miRNAs and their functional role in RDEB fibrosis. miRNA analysis will be the starting point to identify and disentangle novel druggable targets/pathway for future, innovative anti-fibrotic therapeutic strategies.”

Dr Giovanna Zambruno

Dr Zambruno

Dr. Zambruno graduated in Medicine at the University of Pavia, Italy (1982) and completed her residency training in Dermatology and Venereology in 1985 at the same University. Following a research fellowship at the INSERM Laboratory of Dermatological and Immunological Research and at the Department of Dermatology of Claude Bernard University, Lyon, France (1985-1986), she became staff member at the Department of Dermatology, University of Modena, where she established her first research group. In 1995, she moved to the Istituto Dermopatico dell’Immacolata (IDI), where she was Director of the Laboratory of Molecular and Cell Biology (1995-2015) and then Scientific Director (2017-2018). She is currently consultant at Bambino Gesù Children’s Hospital, Rome, where she collaborates with the Pathology and Dermatology Units and the Genetics and Rare Diseases Research Division. Over the past 25 years her clinical and research activity has been focused on rare skin diseases, in particular inherited epidermolysis bullosa. She has authored over 270 publications in peer-reviewed journals, 80 of which on epidermolysis bullosa.