Functional Cell Biology

MEDICAL BIOTECHNOLOGY

Research Interests

Systematic use of innovative High Throughput Screening (HTS) based approaches to dissect complex biological  processes, both in normal and pathological conditions.

Description of Research

Our Research focus is on respiratory diseases and regenerative medicine,  with a specific interest on lung idiopathic pulmonary fibrosis (IPF). IPF is a chronic, progressive Interstitial Lung Disease (ILD) with unknown aetiology in which gradual fibrotic scarring of the lungs leads to usual interstitial lung pneumonia (UIP) and ultimately to death. Several studies support the evidence that multiple insults to the lung tissue followed by inadequate repair due to abnormal response of type-II alveolar epithelial cells (ATII) may stimulate IPF onset. The main trigger for the “pathological activation” of ATII cells still remain unclear, nevertheless aging processes have been shown to induce a specific phenotype that is characterised by replicative arrest and the aberrant secretion of profibrotic senescence-associated factors. This phenotype is called senescence-associated secretory phenotype, SASP. In Humans, it is known that senescent cells with evident SASP accumulate with age in adult lungs; these cells exert autocrine and paracrine effects resulting in increased dysfunction, and/or senescence of neighbouring cells.

Biological therapies for patients with IPF are urgently needed and our research activity focuses mainly on the systematic application of HTS phenotypic screening to identify novel molecules potentially translatable as novel IPF treatments. In particular our research plan is structured around 3 main general goals: 1) “To block” the paracrine pro-fibrotic loop between ATII cells and lung fibroblasts; 2) “To Remove” the source of pro-fibrotic factors by selectively killing senescent ATII cells, and 3) “To revert” the senescent phenotype of ATIIs by restoring ATII’s proliferative capacity.

Recent Publications

Buratti, E. et al. Deferoxamine mesylate improves splicing and GAA activity of the common c.-32-13T>G allele in late-onset PD patient fibroblasts. Mol Ther Methods Clin Dev 20, 227-236, doi:10.1016/j.omtm.2020.11.011 (2021).

Bussani, R. et al. Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology. EBioMedicine 61, 103104, doi:10.1016/j.ebiom.2020.103104 (2020).

Papa, G. et al. CRISPR-Csy4-Mediated Editing of Rotavirus Double-Stranded RNA Genome. Cell Rep 32, 108205, doi:10.1016/j.celrep.2020.108205 (2020).

Braga, L. et al. Non-coding RNA therapeutics for cardiac regeneration. Cardiovasc Res, doi:10.1093/cvr/cvaa071 (2020).

Moimas, S. et al. miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation. ERJ Open Res 5, doi:10.1183/23120541.00138-2019 (2019).

Rehman, M. et al. High-throughput screening discovers antifibrotic properties of haloperidol by hindering myofibroblast activation. JCI Insight 4, doi:10.1172/jci.insight.123987 (2019).