The management and treatment of pelvic organ prolapse in the United States currently exceeds one billion dollars in costs annually. Elastin, the principle protein component of the elastic fiber, imparts vertebrate tissues such as the heart, lungs and skin with remarkable elasticity. The loss of elastin architecture and function is a pathological characteristic of a number of human degenerative and genetic disorders, and is believed to play a critical role in the vagina and in the pathophysiology of pelvic organ prolapse. The central hypothesis of this proposal is that vaginal birth degrades structural and dynamical properties of vaginal elastin compared to cesarean delivery. The objectives of this proposal are to quantitatively investigate the effects of modes of delivery on the structure of elastin of the vagina by pursuing two independent aims.
The first aim of the proposal is to measure the structural and dynamical properties of lysine, proline, valine, glycine and alanine rich segments of elastin of the vagina following various modes of delivery. A key characteristic of this protein that distinguishes it from other elastomers is that its function hinges on hydration only hydrated elastin retains its elasticity.
The second aim of the proposal is to measure the dynamics of water in vaginal elastin following various modes of delivery. This project will make use of nuclear magnetic resonance methods for these measurements. The proposal is interdisciplinary and encompasses biology, chemistry and physics. The methodology includes conventional carbon-13 nuclear magnetic resonance techniques that rely on magic angle spinning technology. In addition, the project will involve the use of non-commercial pulsed gradient fields, developed by the PI, to study time-dependent diffusion of water in elastin. The PI of the proposal is an Assistant Professor of Physics with significant expertise in nuclear magnetic resonance methodology and research experience in elastin. The PI was previously funded for four years under an NIH SC1 proposal. This proposal is a renewal application requesting four additional years of funding. This continued funding will assist the PI to transition to non-SCORE support by following a stepwise developmental plan provided in the biosketch.
The aim of this effort is to investigate the effects of mode of birth on elastin degradation in the vagina, using a murine model. The findings of this study will provide detailed insight into the role of elastin degradation, resulting from different modes of delivery, in pelvic organ prolapse. This innovative study will offer a paradigm for clinicians to measure exactly the effects of various interventions on vaginal elastin structure.
|Bilici, Kubra; Morgan, Steven W; Silverstein, Moshe C et al. (2016) Mechanical, structural, and dynamical modifications of cholesterol exposed porcine aortic elastin. Biophys Chem 218:47-57|
|Dhital, Basant; Gul-E-Noor, Farhana; Downing, Keith T et al. (2016) Pregnancy-Induced Dynamical and Structural Changes of Reproductive Tract Collagen. Biophys J 111:57-68|
|Gul-E-Noor, Farhana; Singh, Chandan; Papaioannou, Antonios et al. (2015) The Behavior of Water in Collagen and Hydroxyapatite Sites of Cortical Bone: Fracture, Mechanical Wear, and Load Bearing Studies. J Phys Chem C Nanomater Interfaces 119:21528-21537|
|Papaioannou, A; Louis, M; Dhital, B et al. (2015) Quantitative comparison of structure and dynamics of elastin following three isolation schemes by 13C solid state NMR and MALDI mass spectrometry. Biochim Biophys Acta 1854:391-401|
|Shen, Ming; Roopchand, Rabia; Mananga, Eugene S et al. (2015) Revisiting NMR composite pulses for broadband (2)H excitation. Solid State Nucl Magn Reson 66-67:45-8|
|Silverstein, Moshe C; Bilici, KÃ¼bra; Morgan, Steven W et al. (2015) 13C, 2h NMR studies of structural and dynamical modifications of glucose-exposed porcine aortic elastin. Biophys J 108:1758-72|
|Shen, Ming; Roopchand, Rabia; Mananga, Eugene S et al. (2015) Theoretical calculation of a composite pulse for (2)H broadband excitation by average Hamiltonian theory. Bo Pu Xue Za Zhi 32:373-381|
|Downing, Keith T; Billah, Mubashir; Raparia, Eva et al. (2014) The role of mode of delivery on elastic fiber architecture and vaginal vault elasticity: a rodent model study. J Mech Behav Biomed Mater 29:190-8|
|Watanabe, Eiji; Boutis, Gregory S; Sato, Hiroko et al. (2014) NMR Studies of Thermo-responsive Behavior of an Amphiphilic Poly(asparagine) Derivative in Water. Polymer (Guildf) 55:278-286|
|Ukpebor, Obehi T; Shah, Anup; Bazov, Emanuel et al. (2014) Inverse temperature transition of elastin like motifs in major ampullate dragline silk: MD simulations of short peptides and NMR studies of water dynamics. Soft Matter 10:773-85|
Showing the most recent 10 out of 19 publications