Transcription of nucleic acids (DNA and RNA) is a hallmark of life, taking the information stored within genomic nucleic acids and converting it into a form that is useful for producing the proteins necessary for cellular and organismal function. In eukaryotes, transcription of DNA into messenger RNA (mRNA) requires the...
When properly regulated, inflammation leads to the recruitment and activation of circulating leukocytes to maintain and restore tissue homeostasis. Although this process is critical for successful wound healing and the elimination of pathogens and infections, misdirected inflammation can exacerbate pathology and cause substantial morbidity and mortality. Inflammation a fundamental process...
The insulin/Insulin-Like Growth Factor (IGF) pathway is essential for linking nutritional status to growth and metabolism. MicroRNAs (miRNAs) are short RNAs that are players in the regulation of this process. The miRNA miR-7 shows highly conserved expression in insulin-producing cells across the animal kingdom. However, its conserved functions in regulation...
The evolutionarily conserved COMPASS family of methyltransferases implements histone H3 lysine 4 (H3K4) methylation, an epigenetic mark associated with transcriptional activation. Given the high mutational prevalence of COMPASS subunits across cancers and neurodevelopmental disorders, understanding COMPASS function would lend important insights into disease pathogenesis to facilitate development of effective therapies....
Uterine leiomyomas (fibroids) are a major source of gynaecologic morbidity in reproductive age women and are characterised by the excessive deposition of a disorganised extracellular matrix, resulting in rigid benign tumours. Clinically, leiomyoma patients usually present with pelvic pain, urinary incontinence, as well as heavy cyclic and non-cyclic bleeding. Curative...
Although centrosomes nucleate and organize microtubules in mitotically-dividing cells, spindles in female reproductive cells (oocytes) form in their absence. In some organisms acentrosomal spindle assembly is mediated by acentriolar microtubule organizing centers (MTOCs) that are thought to functionally replace centrosomes. However, spindle assembly in human oocytes does not require MTOCs;...
Heart failure due to genetic cardiomyopathy is associated with a range of phenotypic expression. The studies in this body of work interrogated the role of noncoding variation in modifying cardiomyopathy phenotypes. We used cap analysis of gene expression in heathy and failed left ventricles to define the regulatory environment of...
This dissertation focuses on the development of quantitative approaches for characterizing endogenous signaling pathways and designing new pathways in mammalian cells. I demonstrate how mathematical descriptions that are formulated to explain gene expression patterns can also serve as a powerful springboard for deeper analyses into the properties and functions of...
Proper partitioning of mitochondria and mtDNA is critical for cellular health. Investigations into mitochondrial inheritance, specifically how mtDNA inheritance is coupled with the inheritance mitochondrial compartment, are still in the early stages. We use budding yeast as a model polarized cell system to study a mitochondrial Myo2-adaptor protein, Mmr1, in...
Bacteria often coordinate virulence factors to fine-tune the host response during infection. These coordinated events can include toxins counteracting or amplifying effects of another toxin or though regulating the stability of virulence factors to remove their function once it is no longer needed. Multifunctional autoprocessing repeats-in toxin (MARTX) toxins are...