My postdoctoral researched looked at the mechanical and physiological drivers of preterm birth. I focused on the effects of S-nitrosation in the human myometrium and specifically the role of gap junction proteins (Cx43) in S-nitrosation mediated tissue relaxation. Cx43 post translational modifications help regulate protein localization, degradation and the potential formation of gap junctions. Protein phosphorylation of the C-terminal domain of Cx43 can occur on 18 serine/threonine sites and two tyrosine sites. Additionally, modification of cysteine residues by nitric oxide (nitrosation) is part of the cGMP independent tissue response to NO exposure and modification of Cx43 at cysteine 271 and the E1 and E2 loops may function to increase relaxation of myometrial tissue. It is currently unknown how this modification affects protein binding and/or function.
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Papers:
Source of Support:
Nevada IDeA Network of Biomedical Research Excellences (INBRE)
Title:
NV INBRE Service Award for the Mick Hitchcock Ph.D. Nevada Proteomics Center
Description of Project:
Our preliminary phospho-proteomic analysis of cultured uterine myometrial cells identified phosphorylation of proteins representative of ERK1/2 and p38 MAPK pathway activation in response to mechanical stretch. The goal of this project is to determine how mechanical stretch affects signal transduction pathways in human uterine myometrium and contributes to development of a contractile phenotype by comparing uterine smooth muscle from twin pregnancies and singleton pregnancies of similar gestational age. We hypothesize the ERK1/2 and p38 MAPK pathways have increased activation in human twin pregnancies and contribute to the increased preterm birth risk.