John J. Moore, MD
Professor, Pediatrics and Reproductive Biology, Case Western Reserve University
For the last 20 years I have been funded by NIH, the March of Dimes, and the Burroughs Wellcome Fund for studies of fetal membrane biochemistry and biomechanics. These studies have focused on correlation of the mechanical properties of the fetal membranes with biochemical characteristics. Specifically, I have developed an ex-vivo model system using human fetal membranes to study the details of the weakening process fetal membranes go through to rupture in response to inflammation/infection and decidual bleeding. This has led to our finding that GM-CSF is the critical intermediate that is both necessary and sufficient for inflammation/bleeding induced fetal membrane weakening. In addition, we have studied the effects of possible inhibitors of the weakening process and demonstrated how each agent blocks GM-CSF production, GM-CSF downstream action or both. We have been concerned that our research to date implies that minor local inflammatory challenges could result in fetal membrane rupture and preterm birth. Some mechanism to push back against this process seemed necessary. Our new data suggests a progesterone mediated, inducible negative feedback system exists locally at the fetal-maternal interface. We are very excited to explore the ramifications of this. A NIH RO1 Grant submitted June 2020 and is pending review.
2015-2019 Burroughs Wellcome Fund #1015024, Prematurity Research Grant, Principal Investigator.
2013-2018 March of Dimes - (National) MOD Prematurity Research Center Ohio
Collaborative; Theme IV – Progesterone, Co-Investigator.
2011-2017 March of Dimes – National #21-FY11-9, AND #21-FY15-124: Determination of the mechanism of preterm premature fetal membrane rupture using a novel in-vitro model system. Principal Investigator
Complete list of published works in My Bibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/john.moore.2/bibliography/48029180/public/
Selected Recent Publications
1. Kumar D, Moore RM, Mercer BM, Mansour JM, Moore JJ. Mechanism of Human Fetal Membrane Biomechanical Weakening, Rupture and Potential Targets for Therapeutic Intervention. Obstet Gynecol Clin N Am. 2020 Dec;47(4):523-544. doi: 10.1016/j.ogc.2020.08.010. Review. PubMed PMID: 33121643.
2. Moore RM, Khatri R, Kumar D, Mansour JM, Mercer B, Moore JJ. α-Lipoic acid blocks the GMCSF induced protease/protease inhibitor spectrum associated with fetal membrane weakening in-vitro. Placenta. 2020; 97:79-88.
3. Sinkey RG, Ozlem Guzeloglu-Kayisli, Sefa Arlier, Xiaofang Guo, Nihan Semerci, Robert Moore; Asli Ozmen, Kellie Larsen, Chinedu Nwabuobi, Deepak Kumar; John J. Moore; Lynn F. Buckwalder, Frederick Schatz, Umit A. Kayisli,; Charles J. Lockwood. Thrombin-Induced Decidual Colony Stimulating Factor-2 (CSF-2) Promotes Abruption-Related Preterm Birth by Weakening Fetal Membranes. American Journal of Pathology. Am J Pathol. 2020 Feb;190(2):388-399.
4. Sharma A, Kumar D, Moore RM, Deshmukh A, Mercer BM, Mansour JM, Moore JJ. Granulocyte macrophage colony stimulating factor (GM-CSF), the critical intermediate of inflammation-induced fetal membrane weakening, primarily exerts its weakening effect on the choriodecidua rather than the amnion. Placenta. 2019 Oct 5; 89:1-7.
5. Kumar D, Moore RM, Sharma A*, Mercer BM, Mansour JM, Moore JJ. In an in-vitro model using human fetal membranes, α-lipoic acid inhibits inflammation induced fetal membrane weakening. Placenta. 2018; 68: 9-14.