Biochemistry, Biophysics, and Structural Biology Commons^™

Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu

Electronic Thesis and Dissertation Repository

Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.

I found that …

Maternal Control Of Genomic Imprinting: Effects Of Infertility And Ovarian Stimulation In A Mouse Model, Michelle M. Denomme

Electronic Thesis and Dissertation Repository

Gametogenesis and early embryogenesis are important stages in which genome-wide epigenetic transitions required for early mammalian development are orchestrated. This is exemplified by the occurrence of genomic imprinting, where epigenetic mechanisms lead to the monoallelic expression of a subset of genes. Parental-specific DNA methylation in the gametes results in the distinct nonequivalence of the parental genomes in the early embryo. Changes from normal gamete and embryo development by impaired fertility or assisted reproductive technologies (ARTs) may disrupt the processes of imprint acquisition and imprint maintenance. My hypothesis is that aberrant imprinted methylation arises from impaired maternal fertility or ovarian stimulation …

Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, Christine Di Cresce

Electronic Thesis and Dissertation Repository

Thymidylate synthase (TS) is the only de novo source of thymidylate (dTMP) for DNA synthesis and repair. Drugs targeting TS protein are a mainstay in cancer treatment but off-target effects and toxicity limit their use. Cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2) contribute to an alternative dTMP-producing pathway, by salvaging thymidine from the tumour milieu, and may modulate resistance to TS-targeting drugs. We have previously shown that TS antisense molecules (oligodeoxynucleotides, ODNs, and small interfering siRNA, siRNA) sensitize tumour cells, both in vitro and in vivo, to TS targeting drugs. As both TS and TKs contribute to cellular …