Assistant Professor of Pediatrics
Research DescriptionWe are interested in understanding the molecular regulation of an essential blood vessel known as the ductus arteriosus (DA). This vessel shunts blood away from the underdeveloped lungs and directs it into the systemic circulation so that it can get oxygenated by the placenta during fetal life. However at birth, this vessel must constrict and seal itself off in order to establish proper blood flow to the lungs. In some cases, the ductus fails to close, a condition termed patent ductus arteriosus (PDA). PDA is a significant cardiovascular disorder affecting 1 out of every 500-2000 term infants and 30-40% of the most critically ill premature neonates. Presently, the pharmacological therapies for PDA are limited, have adverse side effects, and are not specifically targeted to the DA. Therefore, one of the main focuses of our lab is to identify factors that set the DA apart from other vessels in the body in the hopes of developing novel DA-specific therapeutic regulators of vascular tone. We use a combination of primary cell culture models, cannulated vessel myography assays, and whole animal models to identify factors that constrict or relax the DA.
Another interest of our lab is to identify non-vascular cell types that can be used to form new vasculature or repair injured vessels. Using in vivo mouse models and cell culture systems, we have demonstrated that mesothelium, a simple epithelium, has the potential to differentiate into vascular smooth muscle and endothelial cells that can be used for vessel repair. In collaboration with members of the department of bioengineering, we are using microfluidic bioreactors to investigate the effects of flow, cyclic stretching, and matrix composition on the ability of mesothelia to differentiate into vascular cells as well as other cell types including bone and cartilage. Furthermore, we are interested in identifying genetic signatures for different populations of normal and pathological mesothelia. Understanding the nature of these cells will be useful in maximizing their therapeutic potential in tissue repair as well as provide new ways to limit their ability to form fibrotic lesions or tumors.
- Reese J, Shelton EL, Slaughter JC, McNamara PJ. Prophylactic Indomethacin Revisited [editorial]. J. Pediatr [print-electronic]. 2017 Jul; 186: 11-14.e1. PMID: 28396028, PMCID: PMC5520627, PII: S0022-3476(17)30385-2, DOI: 10.1016/j.jpeds.2017.03.036, ISSN: 1097-6833.
- Hooper CW, Delaney C, Streeter T, Yarboro MT, Poole S, Brown N, Slaughter JC, Cotton RB, Reese J, Shelton EL. Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2016 Sep 9/1/2016; 311(3): H572-81. PMID: 27371685, PMCID: PMC5142184, PII: ajpheart.00822.2015, DOI: 10.1152/ajpheart.00822.2015, ISSN: 1522-1539.
- Waleh N, Barrette AM, Dagle JM, Momany A, Jin C, Hills NK, Shelton EL, Reese J, Clyman RI. Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression. J. Pediatr [print-electronic]. 2015 Nov; 167(5): 1033-1041.e2. PMID: 26265282, PMCID: PMC4661123, PII: S0022-3476(15)00733-7, DOI: 10.1016/j.jpeds.2015.07.011, ISSN: 1097-6833.
- Herington JL, Swale DR, Brown N, Shelton EL, Choi H, Williams CH, Hong CC, Paria BC, Denton JS, Reese J. High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility. PLoS ONE. 2015; 10(11): e0143243. PMID: 26600013, PMCID: PMC4658040, PII: PONE-D-15-12311, DOI: 10.1371/journal.pone.0143243, ISSN: 1932-6203.
- El-Khuffash A, Jain A, Corcoran D, Shah PS, Hooper CW, Brown N, Poole SD, Shelton EL, Milne GL, Reese J, McNamara PJ. Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies. Pediatr. Res [print-electronic]. 2014 Sep; 76(3): 238-44. PMID: 24941212, PMCID: PMC4321957, PII: pr201482, DOI: 10.1038/pr.2014.82, ISSN: 1530-0447.
- Vucovich MM, Cotton RB, Shelton EL, Goettel JA, Ehinger NJ, Poole SD, Brown N, Wynn JL, Paria BC, Slaughter JC, Clark RH, Rojas MA, Reese J. Aminoglycoside-mediated relaxation of the ductus arteriosus in sepsis-associated PDA. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2014 Sep 9/1/2014; 307(5): H732-40. PMID: 24993047, PMCID: PMC4187398, PII: ajpheart.00838.2013, DOI: 10.1152/ajpheart.00838.2013, ISSN: 1522-1539.
- Shelton EL, Ector G, Galindo CL, Hooper CW, Brown N, Wilkerson I, Pfaltzgraff ER, Paria BC, Cotton RB, Stoller JZ, Reese J. Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone. Physiol. Genomics [print-electronic]. 2014 Jul 7/1/2014; 46(13): 457-66. PMID: 24790087, PMCID: PMC4080279, PII: physiolgenomics.00171.2013, DOI: 10.1152/physiolgenomics.00171.2013, ISSN: 1531-2267.
- Pfaltzgraff ER, Shelton EL, Galindo CL, Nelms BL, Hooper CW, Poole SD, Labosky PA, Bader DM, Reese J. Embryonic domains of the aorta derived from diverse origins exhibit distinct properties that converge into a common phenotype in the adult. J. Mol. Cell. Cardiol [print-electronic]. 2014 Apr; 69: 88-96. PMID: 24508561, PMCID: PMC4034360, PII: S0022-2828(14)00036-4, DOI: 10.1016/j.yjmcc.2014.01.016, ISSN: 1095-8584.
- Shelton EL, Poole SD, Reese J, Bader DM. Omental grafting: a cell-based therapy for blood vessel repair. J Tissue Eng Regen Med [print-electronic]. 2013 Jun; 7(6): 421-33. PMID: 22318999, PMCID: PMC3672266, DOI: 10.1002/term.528, ISSN: 1932-7005.
- Cotton RB, Shah LP, Poole SD, Ehinger NJ, Brown N, Shelton EL, Slaughter JC, Baldwin HS, Paria BC, Reese J. Cimetidine-associated patent ductus arteriosus is mediated via a cytochrome P450 mechanism independent of H2 receptor antagonism. J. Mol. Cell. Cardiol [print-electronic]. 2013 Jun; 59: 86-94. PMID: 23454087, PMCID: PMC3646934, PII: S0022-2828(13)00067-9, DOI: 10.1016/j.yjmcc.2013.02.010, ISSN: 1095-8584.
- Shelton EL, Galindo CL, Williams CH, Pfaltzgraff E, Hong CC, Bader DM. Autotaxin signaling governs phenotypic heterogeneity in visceral and parietal mesothelia. PLoS ONE [electronic-print]. 2013; 8(7): e69712. PMID: 23936085, PMCID: PMC3723636, PII: PONE-D-13-15224, DOI: 10.1371/journal.pone.0069712, ISSN: 1932-6203.
- Shelton EL, Bader DM. Thymosin ß4 mobilizes mesothelial cells for blood vessel repair. Ann. N. Y. Acad. Sci. 2012 Oct; 1269: 125-30. PMID: 23045980, PMCID: PMC3693742, DOI: 10.1111/j.1749-6632.2012.06713.x, ISSN: 1749-6632.