Young Kwon, Ph.D. - US grants

ABSTRACT
International Workshop on
Predictive Modelling of Composite Materials
Project Summary, NSF Proposal # CMS-0622381

The essence of the Meeting through the presentation of plenary papers only and specialized workshops, is the identification and subsequent avoidance of all conceivable sources of weakness at the nano and micron level of material architecture; and when coupled with methods of predictive design to the complete prevention of misfortune of composite structure metres in length.

Attention focuses on how to optimize designed microstructures, nano-architectural materials, MEMS and smart materials, and information technology materials. Reporting on observed phenomena and presenting critical measured experimental data, making links between compatible modeling techniques and predicting behavior are vital ingredients to a successful totally integrated material/structure design methodology. Built into physical models will be those essential processing variables that lead to new and innovative fabrication methods.

Bringing together key academicians with partners in the aerospace and related industries, for example, will significantly improve the basis for testing, evaluation and certification methodologies, thereby unlocking the timely opportunities in scientific achievement and new product introduction in aerospace.

DESCRIPTION (provided by applicant): This Phase-II proposal seeks to elucidate the structure-function relationships between visual field threshold sensitivity and the structural features of the retinal layers, the optic nerve head, and the connecting nerve fiber bundles in glaucoma. This proposal extends our successful Phase-I research that established structure- structure relationships among retinal quantitative indices. In this Phase II, further advancements of spectral domain optical coherence tomography (SD OCT) image analysis will yield new damage metrics expected to correspond much better with visual field threshold sensitivity. The project is driven by an important clinical problem - the poor reliability and reproducibility of th visual field as a measure of irreversible damage to the retinal ganglion cells and their axons in glaucoma. Our long-term vision remains to determine/predict glaucoma visual function from objective structure measurements by OCT. Once achieved, this new approach will provide an objective and reproducible measure, complementing subjective functional assessment of glaucoma damage, decrease the need for frequent visual field testing resulting from long-term fluctuation of visual response, and improve glaucoma treatment based on reliable progression markers. Specifically, we will develop predictive models of increasing complexity yielding a patient- specific predictive model of glaucomatous damage. The overriding hypothesis motivating the proposed research is that novel quantitative metrics of the entire retinal ganglion cell-axonal complex morphology utilizing the nerve fiber bundle trajectories allow reliable prediction of visual function. We have identified the following specific aims: Aim 1: Establish a baseline for the focal structural-functional correlation in the retina covered by the Humphrey 24-2 perimetry test (24 degree radius visual field) by comparing 24-2 thresholds with their corresponding structural indices derived from registered multi-field SD-OCT scans in glaucoma and normal subjects. Derive a baseline predictive model of function from structural properties of the inner retinal layers, comprised of retinal ganglion cell and nerve fiber layers. Aim 2: Demonstrate that incorporating structural parameters along SD-OCT atlas-based retinal ganglion cell- axonal complex (RGC-AC) trajectories improves the performance of the predictive structure-function model. Aim 3: Evaluate whether prediction of 24-2 thresholds is improved by deriving individual-based RGC-AC trajectories instead of from an RGC-AC atlas. The proposed work will be performed using 7-field per eye 3D SD-OCT images accompanied by 24-2 visual field test data on the same day from 100 patients with glaucoma and 40 age-matched normal subjects.

Project Summary Maintaining epithelial homeostasis is crucial for organismal health since disruption of epithelial homeostasis promotes many human diseases, including cancers. Unnecessary, defective, or potentially harmful cells can be eliminated from epithelia by ?cell extrusion??a process to remove cells from epithelia without disrupting its barrier function. Previous studies have shown that cells can extrude from epithelia either apically or basally. Since the apical side of epithelia faces the outside or lumen, extrusion of cells toward the apical side generally leads to the shedding of extruded cells. In contrast, oncogenic transformation can make cells extrude toward basal side of the epithelia. When these basally extruded cells do not die off, they can spread to stroma and/or other tissues, which can be deleterious to the tissue and organism as a whole. Although basal cell extrusion is a crucial process for maintaining tissue homeostasis and initiating cancer metastasis, its cellular and molecular mechanisms are poorly understood. We have recently established a new Drosophila intestinal model of basal cell extrusion. We discovered that intestinal stem cells expressing oncogenic Ras (RasV12) extruded basally from intestinal epithelia in adult Drosophila. This model provides us a unique opportunity to uncover the fundamental mechanisms impinging on basal-cell extrusion using the state-of-the-art genomic and genetic tools available in Drosophila. With this model, we propose to address a few outstanding questions in the field: (1) we will define the cellular processes required for basal cell extrusion and determine their signaling networks; (2) we will scrutinize another long- standing question that epithelial-mesenchymal transition, a tumor-promoting process, is required for basal cell extrusion; and (3) we will elucidate the role of innate immune cells in the elimination of transformed cells via basal cell extrusion. Discovering the molecular basis underlying basal cell extrusion will help us to learn how to tweak the process to keep epithelia healthy and to prevent tumor metastasis.