The opposing activities of phosphatases and kinases determine the phosphorylation status of proteins, yet kinases have received disproportionate attention in studies of cellular processes, with the roles of phosphatases remaining less understood. This dissertation describes the use of self-assembled monolayer laser desorption/ionization mass spectrometry (SAMDI-MS) together with peptide arrays to...
Melanin is a functional biopolymer most commonly associated with human skin pigmentation, where it serves as a radiation protection agent, shielding us from the harmful effects of UV radiation. However, melanin is also present in human ears, eyes, hair, and brains, serving a variety of functions. In fact, melanin...
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...
The interaction of amyloid-β (Aβ) with endogenous metal ions is thought to play a role in the pathogenesis of Alzheimer’s disease (AD). However, limited tools exist to study and modulate Aβ-metal binding. The Meade lab has developed cobalt(III) Schiff base (Co(III)-sb) complexes as protein inhibitors that competitively displace metals from...
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...
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...
Natural products from fungi have had an immeasurable societal impact as both friends and foes to human health. This includes numerous therapeutics that have had widespread clinical success, mycotoxins that are implicated in fungal pathogenicity, and various agrochemicals. Recent genome sequencing efforts have revealed that fungal genomes contain the capacity...
Nucleic acid drugs promise to revolutionize the development of therapeutics. They offer a platform for digital medicine, where systematic changes to the nucleic acid sequence can be utilized to target the entire human genome. However, nucleic acids suffer from a number of drawbacks, such as negligible cellular uptake and rapid...
Proteins represent a critical class of biomolecules, universally employed by all living organisms to fulfill essential structural, functional, and enzymatic roles necessary to support life. In nature, these polymers are composed generally of twenty natural amino acid (AA) building blocks, which can be modified with covalent adducts known as post-translational...