Nationwide Children’s Hospital/Assistant Professor of Pediatrics
My research program as focused on identifying molecular inflammatory targets in necrotizing enterocolitis (NEC)that could lead to novel modulators of the intestinal inflammation characteristic of NEC. The individual differences in patient susceptibility to NEC and its variable severity may be due to abnormalities in the balance of pro-inflammatory and anti-inflammatory mechanisms that contribute to immune homeostasis. In mammals, mitogen activated protein kinases (MAPKs) are primarily deactivated by a family of dual specificity protein phosphatases (DUSP) via dephosphorylation of specific tyrosine and threonine residues. Dusp-1, a nuclear phosphatase, restrains the pro-inflammatory cascade by preferentially negatively regulating p38 and JNK activation. Dusp-6, a cytosolic phosphatase, limits the inflammatory response by preferentially negatively regulating ERK activation. We have investigated genetic links between NEC development and dual specificity phosphatase (DUSP) single nucleotide polymorphisms (SNPs) and isolated three SNPs in the DUSP-6 gene that might confer a susceptibility to NEC development. We continue to investigate the role of DUSP-1 (MKP-1) in NEC development, specifically, mucosal immunity, microbiome development, and barrier dysfunction in an animal model of NEC. In addition, I have embarked in collaboration with virologist and infectious disease specialists, to study the role cytomegalovirus (CMV) plays in intestinal inflammation and NEC development. Using an animal model of NEC, we seek to investigate how CMV infection may exacerbate the intestinal inflammatory cascade contributing to a risk factor to NEC development.
(1) elucidate the role of DUSP-1 and DUSP-6 in intestinal inflammation, microbiome and mucosal immunity in an animal model of NEC
(2) to study the role of cytomegalovirus in the pathogenesis of NEC
(3) determine genetic links between DUSP-1 and DUSP-6 in NEC development
1. Mitogen-activated protein kinase phosphatase-1 prevents lipopolysaccharide-induced apoptosis in immature rat intestinal epithelial cells. Talavera MM, Kralik N, Jin Y, Chen B, Liu Y, Nelin LD.Pediatr Res. 2015 Aug;78(2):128-36. doi: 10.1038/pr.2015.88. PMID: 25950450.
2. Quality Improvement Initiative to Reduce the Necrotizing Enterocolitis Rate in Premature Infants. Talavera MM, Bixler G, Cozzi C, Dail J, Miller RR, McClead R Jr, Reber K. Pediatrics. 2016 May;137(5). pii: e20151119. /peds.2015-1119 PMID: 27244778
3. Immunostimulated Arginase II Expression in Intestinal Epithelial Cells Reduces Nitric Oxide Production and Apoptosis. Talavera MM, Nuthakki S, Cui H, Jin Y, Liu Y, Nelin LD. Front Cell Dev Biol. 2017 Mar 1;5:15. doi: 10.3389/fcell.2017.00015. PMID: 28299311
4. Transient effects of transfusion and feeding advances (volumetric and caloric) on necrotizing enterocolitis development: A case-crossover study. Le VT, Klebanoff MA, Talavera MM, Slaughter JL.PLoS One. 2017 Jun 20;12(6):e0179724. doi: 10.1371/journal.pone.0179724. PMID: 28632783.
5. Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis. Gross Margolis K, Vittorio J, Talavera M, Gluck K, Li Z, Iuga A, Stevanovic K, Saurman V, Israelyan N, Welch MG, Gershon MD. Am J Physiol Gastrointest Liver Physiol. 2017 Nov 1;313(5):G386-G398. doi: 10.1152/ajpgi.00215.2017. PMID: 28774871