Medicine and Health Sciences Commons^™

Characterization And Functional Rescue Of Congenital Muscular Dystrophy With Megaconial Myopathy In A Mouse Model Of The Disease, Ambreen A. Sayed

Electronic Theses and Dissertations

Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. Megamitochondria in skeletal muscle biopsies and cognitive impairments in MDCMC patients are observations exclusive to this type of muscular dystrophy. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine (PC). A rostro-caudal muscular dystrophy (rmd) mouse with a deletion in the Chkb gene resulting in MDCMC-like symptoms has been reported by our lab. In order to test if the rmd mice …

Modeling Human Cancer Therapy Response In Patient Derived Xenografts, Joan Malcolm

Electronic Theses and Dissertations

Patient‐derived xenografts (PDXs) generated by implanting human tumor tissue into a transplant compliant mouse host have been of increasingly importance to preclinical development and have been demonstrated to have advantages compared to cancer cell lines and cell‐line xenografts (CLX) for modeling therapeutic responses in cancer. Nevertheless, many open questions remain regarding the relationship between study design factors and classification of treatment response and the molecular fidelity of tumors passaged in PDXs relative to the original patient tumor(s). The research described in this dissertation addresses both of these significant issues related to the use of PDXs as a tool for modeling …

Genetic Modification Of Inherited Retinopathy In Mice, Yang Kong

Electronic Theses and Dissertations

The retina, as a critical component of the sensory system, consists of multiple cell types, of which, photoreceptors play a key role in receiving, integrating and transmitting light signals. The biofunctions of photoreceptors rely on their proper growth and development, which is predominantly governed by a cluster of molecules that comprise the transcriptional regulation for photoreceptor development. Any disruption of these molecules potentially incurs retinal pathologies.

It is known that deficiencies of nuclear receptor subfamily 2 group E member 3 (NR2E3) or neural retina leucine-zipper (NRL), two molecules in regulating photoreceptor cell development, cause photoreceptor dysplasia. In a sensitized chemical …

Characterizing The Role Of Fungal Shape In A Zebrafish Model Of Invasive Candidiasis, Brittany Seman

Electronic Theses and Dissertations

Candida albicans is a common hospital-acquired fungal infection, and disseminated disease claims up to one-half of those afflicted. C. albicans has a unique ability to differentiate its shape during infection, and this differentiation is thought to be a major virulence factor during invasive infections. Each shape is proposed to have a specialized role: filaments drive tissue invasion and yeast mediate dissemination to the bloodstream. However, it has been difficult to test these hypotheses for two reasons. First, rigorous testing of shape-specific roles requires diverse strategies of shape modulation that restrict the possibility of manipulation-specific artifacts. Second, although connecting shape to …