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 focuses on respiratory diseases and regenerative medicine, with a specific interest in chronic lung conditions that represent a major and growing burden worldwide, including Idiopathic Pulmonary Fibrosis (IPF) and Chronic Obstructive Pulmonary Disease (COPD). These conditions are particularly relevant for low and middle-income countries (LMICs), where exposure to major risk factors such as ambient and household air pollution, occupational exposures, tobacco use, and recurrent respiratory infections is highly prevalent, while access to advanced diagnostics and effective disease-modifying therapies remains limited. In LMICs, IPF and other fibrotic interstitial lung diseases (ILDs) are also likely underdiagnosed, to advanced imaging systems (HRCT scans), and yet represent a major unmet need due to rapidly ageing populations and restricted access to therapy.

IPF is a chronic, progressive interstitial lung disease of unknown aetiology, characterised by irreversible fibrotic scarring that compromises gas exchange and lung function, and is associated with the radiological and/or histopathological pattern of usual interstitial pneumonia (UIP) and poor clinical outcome. A large body of evidence supports the model that repeated epithelial injury followed by inadequate repair, driven in part by abnormal responses of alveolar type II epithelial cells (ATII), contributes to disease initiation and progression. The upstream triggers that lead to pathological ATII activation remain incompletely understood; however, ageing-associated mechanisms can promote a dysfunctional epithelial state characterised by cell cycle arrest and aberrant secretion of pro-inflammatory and pro-fibrotic mediators. This is closely linked to cellular senescence and the senescence-associated secretory phenotype (SASP). In humans, senescent cells accumulate in the ageing lung and can exert strong autocrine and paracrine effects, promoting tissue dysfunction and propagating senescence and fibrotic signalling to neighbouring cells.

Importantly, related mechanisms, including chronic epithelial injury, impaired repair, and accelerated lung ageing, are increasingly recognised also in  COPD, which is among the leading causes of morbidity and mortality in LMICs. Notably, the World Health Organization reports that approximately 90% of COPD deaths in individuals under 70 years of age occur in LMICs.

New biological therapies for chronic lung diseases are urgently needed, particularly interventions that can be translated into scalable and affordable solutions compatible with LMIC healthcare systems. Our research therefore focuses on the systematic application of phenotypic High Throughput Screening (HTS) platforms to identify novel therapeutic candidates, with a specific interest in mechanisms that control epithelial injury responses, and regeneration.

Our research plan mainly focuses on IPF and COPD and is structured around three main goals:

• To revert epithelial dysfunction by restoring ATII regenerative capacity, promoting effective alveolar repair and functional lung regeneration.
• To block the paracrine pathological signalling loop between ATII cells and lung fibroblasts, thereby preventing amplification of pro-fibrotic and tissue remodelling pathways.
• To remove the source of pathological mediators by selectively eliminating dysfunctional ATII cells that drive chronic inflammation and fibrosis.

Recent Publications