Medicine and Health Sciences Commons^™

Toward Personalized Medicine: The Potential Role Of Rna Interference In Plasma Cell Dyscrasia, Jonathan E Phipps

Doctoral Dissertations

A major contributor to mortality in patients with plasma cell dyscrasias (PCDs); i.e., multiple myeloma, light chain deposition disease and AL amyloidosis is the deposition as insoluble aggregates of monoclonal immunoglobulin light chain proteins (LC) in the kidneys and other organs. Currently anti-plasma cell chemotherapies are used to reduce LC synthesis, and slow deposition. While effective, these treatments are toxic, non-specific, expensive, and might not be appropriate in all cases, making the identification of an alternate means of reducing toxic LC species desirable. To this end, we have investigated whether RNA interference (RNAi) could achieve these goals.

Human (RPMI 8226, …

Immunologic Risk Prediction Model For Kidney Graft Function, Christina Diane Bishop

Doctoral Dissertations

Clinicians lack appropriate non-invasive methods to be able to predict, diagnose, and reduce the risk of rejection in the years following kidney transplantation. Protocol biopsies and monitoring of serum creatinine levels are the most common methods of monitoring graft function after transplant; however, they have several negative aspects. Use of traditional factors regarding donors and recipients such as Human Leukocyte Antigen (HLA) DNA typing, pre-transplant anti-HLA antibody levels, and basic demographics (age, ethnicity/race, gender), has proved inadequate for post-transplant graft monitoring past the first few years. We propose that by utilizing immunologic factors available to clinicians across the United States, …

Role Of Il-17 And Th17 Cells In Hsv Induced Ocular Immunopathology, Amol Sahebrao Suryawanshi

Doctoral Dissertations

Herpes simplex virus (HSV) infection of the cornea leads to a blinding immuno-inflammatory condition of the eye also called stromal keratitis (SK). SK immunopathology is characterized by the infiltration of CD4⁺ T cells of Th1 phenotype as well as the development of new blood vessels into the normally avascular cornea. Studies in mouse models of SK have firmly established the role of CD4⁺ T cells, and particularly of Th1 phenotype, as the principal mediators of SK immunopathology. However, with the recent discovery of IL-17A and Th17 cells, the role of this cytokine as well as Th17 cells remains …

Mechanism Of Phospholipid Induction Of Cell Migration, Dongwei Wu

Doctoral Dissertations

Lysophosphatidic acid (LPA) is a potent bioactive lipid component of oxidized low density lipoproteins (oxLDL). High concentrations of LPA have been detected in human atherosclerotic plaques. Our data has shown that LPA highly induces smooth muscle cell (SMC) migration. Cyr61, a matricellular protein, which also accumulates in human atherosclerotic plaques, has been implicated in the injury-induced neointimal formation. Smooth muscle cell migration is a key event in the development of atherosclerosis, and it contributes to the progressive growth of atherosclerotic lesions. Data generated by this study demonstrate that LPA markedly induces Cyr61 expression in mouse aortic smooth muscle cells (MASMC). …

Development Of An Autonomous Mammalian Lux Reporter System, Daniel Michael Close

Doctoral Dissertations

Since its characterization, the definitive shortcoming of the bacterial luciferase (lux) bioluminescent reporter system has been its inability to express at a functional level in the eukaryotic cellular background. While recent developments have allowed for lux function in the lower eukaryote Saccharomyces cerevisiae, they have not provided for autonomous function in higher eukaryotes capable of serving as human biomedical proxies. Here it is reported for the first time that, through a process of poly-bicistronic expression of human codon-optimized lux genes, it is possible to autonomously produce a bioluminescent signal directly from mammalian cells. The low background of …

Stem Cell Biology And Strategies For Therapeutic Development In Degenerative Diseases And Cancer, Angel A. Alvarez '98

Doctoral Dissertations

Stem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows:

Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human mesenchymal stem cells to an embryonic stem cell-like phenotype.

Aim 2: Demonstrate that induced expression of nanog up-regulates the expression of multiple embryonic stem …