* Necrotizing enterocolitis (NEC):
The main aim is to reduce the morbidity and mortality of NEC by introducing innovative therapies in Paediatric Surgery. The program combines (i) basic science investigations, (ii) translational research and (iii) improvement in health system. This will increase the existing knowledge of the disease mechanism; evaluate novel forms of treatment and create a platform for expedite diagnosis and treatment. The research is based on four main pillars:
To investigate the pathophysiology of NEC
Formula feeding and prematurity are two major risk factors of (NEC) in which hypoxia and inflammation damage the bowel. How formula feeding during prematurity confers a higher risk of NEC is not clear. Insufficient arginine/NO synthesis in immature gut prevents proper formula feeding-induced postprandial hyperaemia and promotes NEC. Our Research uncovered a mechanism for NEC pathogenesis and suggests that balancing intestinal oxygen demand and supply is important to prevent NEC.
To investigate the progression of NEC
Since NEC is associated with prematurity, aberrations in development of intestinal stem cells, targeting these residence cells may provide a therapeutic option for the NEC patient. It is important to understand the regulation of IESC in order to provide insights into intestinal pathogenesis as well as to develop treatments for other intestinal diseases that share some features with NEC. We have shown that IESC is epigenetically regulated by EZH2 (Enhancer of Zeste Homolog-2), a member of Polycomb Repressive Complex, transcriptionally represses expression via histone methylation and deacetylation. We plan to study the role of epigenetic regulation of Intestinal stem cells in NEC progression.
To investigate the role of different mediators in preventing NEC.
Breastfed babies have a lower risk of NEC than those who are formula-fed, but the mechanisms underlying this protection remain unclear. We study the effect from Human Milk Oligosaccharides (HMO), exosome, and Omega3 fatty acids to reduce mucosal injury and lower the NEC incidence.
To investigate the role of different mediators in the treatment of NEC and halting its progression.
The amniotic fluid stem cells (AFSC) and Remote Ischemic Conditioning (RIC) are the two novel treatments we are currently investigating. While the amniotic fluid stem cells may exerts its protective function through Wnt pathway or Prostaglandin E2 (PGE2), Remote Ischemic conditioning (RIC) works through NaHS to regulate Intestinal microcirculation. In addition, we are currently conducting studies to investigate the role of microbiota and enteric neural system (ENS) on the treatment and prevention of NEC.
PCR, real-time PCR, immuno-staining, cell culture, organoids culture, fluorescence imaging, Ussing Chamber, Western Blot, Two-photon laser scanning microscopy, mass spectrometry
PCR and real-time PCR (Bio-rad), Western Blot (Life Tecn logy), Dissecting and Fluorescence microscope (Nikon), Two-photon laser scanning microscopy (Leica), mass spectrometry (Agilent)