Childrens Mercy Hospital Kansas City MO
My interest in research is driven primarily by a need to understand the how? and the why? behind premature infants developing Necrotizing enterocolitis (NEC), a disease I am familiar with clinically. While aberrant activation of innate immune signaling by intestinal microbiota is important for NEC it is unclear why only certain infants develop the disease. The major goal of our research is do understand how genetic risk factors program pathological interactions between intestinal microbiome and host immune pathways observed in NEC. We used genetic approaches, cell culture experiments and experimental mouse models to examine NEC pathogenesis. A major focus is on the role of Single Immunoglobulin Interleukin-1 Related Receptor, an inhibitor or TLR signaling in NEC. We are avidly pursuing studies to study the contribution of SIGIRR mutations to NEC susceptibility as well as examining the role of SIGIRR in regulating microbiome-immune interactions in the gut using a novel mouse model we created. We are also pursuing studies to test various therapies to prevent NEC in cell culture and mouse models.
Genetic basis of NEC susceptibility The Role of SIGIRR in NEC
SIGIRR mutations in premature infants with necrotizing enterocolitis. Sampath V, Menden H, Helbling D, Gastonguay A, Li K, Ramchandran R, Dimmock D. Pediatrics. 2015 Jun;135(6):e1530-4. PMID 25963006
Necrotizing enterocolitis is not associated with sequence variants in Anti-Oxidant Response genes in premature infants. Sampath V, Helbling D, Menden H, Dimmock D, Mulrooney N, Murray J, Dagle J, Garland J. J Pediatr Gastroenterol Nutr. 2016 Mar;62(3):420-3. PMID 26426434.
Alain Cuna, Venkatesh Sampath. Genomic alterations in necrotizing enterocolitis. Semin Perinatol. 2017 Feb;41(1):61-69. doi: 10.1053/j.semperi.2016.09.019. Review. PMID 27836427.
A functional ATG16L1 (T300A) variant is associated with Necrotizing enterocolitis in premature infants. Sampath V, Bhandari V, Berger J, Merchant D, Zhang L, Ladd M, Menden H, Garland J, Ambalavanan N, Mulrooney N, Quasney M, Dagle JM, Lavoie P, Simpson PM, Dahmer M. Pediatr Res. 2017 Apr;81(4):582-588.27893720
Jason Fawley, Alain Cuna, Heather Menden, Steven McElroy, Shahid Umar, Scott Welak, David Gourlay, Xiaoxia Li, and Venkatesh Sampath. Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) Regulates TLR4 Mediated Inflammation in Necrotizing Enterocolitis. Pediatr Res. 2017 Oct 4. [Epub ahead of print]. PMID: 28846670 • Alain Cuna, Tomi Pastinen, Venkatesh Sampath. Genomics of necrotizing enterocolitis. Semin Fetal and Neonatal Med; 2018 Aug 18. S1744-165X(18)30098-2. PMID: 30292709