Agostino Pierro

Keywords: necrotizing enterocolitis, intestinal damage, intestinal epithelium, ischemia and reperfusion of the intestine, tissue engineering, randomized controlled trials, neonatal intestinal development, minimally invasive surgery, nutrition

Research Synopsis

Detailed Description:

* 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.

METHODS USED

PCR, real-time PCR, immuno-staining, cell culture, organoids culture, fluorescence imaging, Ussing Chamber, Western Blot, Two-photon laser scanning microscopy, mass spectrometry

EQUIPMENT USED

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)

Recent Publications

Hall NJ, Eaton S, Abbo O, Arnaud AP, Beaudin M, Brindle M, Bütter A, Davies D, Jancelewicz T, Johnson K, Keijzer R, Lapidus-Krol E, Offringa M, Piché N, Rintala R, Skarsgard E, Svensson JF, Ungar WJ, Wester T, Willan AR, Zani A, St Peter SD, Pierro A. Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial. BMJ Paediatr Open. 2017 May 18;1(1). pii: bmjpo-2017-000028. doi: 10.1136/bmjpo-2017-000028. eCollection 2017. PubMed PMID: 29637088; PubMed Central PMCID: PMC5843002.

Y, Li B, Chen Y, Miyake H, Lee C, Chi L, Wu R, Inoue M, Uchida K, Kusunoki M, Delgado-Olguin P, Pierro A. Live Imaging of Fetal Intra-abdominal Organs Using Two-Photon Laser-Scanning Microscopy. Methods Mol Biol. 2018;1752:63-69. doi: 10.1007/978-1-4939-7714-7_6. PubMed PMID: 29564762.

H, Chen Y, Hock A, Seo S, Koike Y, Pierro A. Are prophylactic anti-reflux medications effective after esophageal atresia repair? Systematic review and meta-analysis. Pediatr Surg Int. 2018 May;34(5):491-497. doi: 10.1007/s00383-018-4242-4. Epub 2018 Mar 13. Review. PubMed PMID: 29536176.

Mutanen A, Pierro A, Zani A. Perioperative Complications Following Surgery for Necrotizing Enterocolitis. Eur J Pediatr Surg. 2018 Apr;28(2):148-151. doi: 10.1055/s-0038-1636943. Epub 2018 Mar 13. PubMed PMID: 29534255.

H, Li B, Lee C, Koike Y, Chen Y, Seo S, Pierro A. Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis. J Pediatr Surg. 2018 Feb 7. pii: S0022-3468(18)30060-5. doi: 10.1016/j.jpedsurg.2018.02.006. [Epub ahead of print] PubMed PMID: 29502797. 6. Lautz TB, Eaton S, Keys L, Ito J, Polo M, Wells JCK, Pierro A, Superina RA. Metabolic profile of children with extrahepatic portal vein obstruction undergoing meso-Rex bypass. J Surg Res. 2018 Mar;223:109-114. doi: 10.1016/j.jss.2017.10.010. Epub 2017 Dec 22. PubMed PMID: 29433861.

Appointments

Cross-Appointed to Physiology, Institute of Medical Science (IMS)
Primary: Surgery
Senior Associate Scientist, The Hospital for Sick Children, Research Institute