Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed in the heart and central nervous system where they regulate membrane excitability. Recently, inhibiting HCN channels in the hippocampus has been identified as a possible therapeutic intervention for the treatment of Major Depressive Disorder (MDD). However, based on the high expression level of...
SAMDI-MS, which stands for self-assembled monolayers (SAMs) for matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS), is a powerful tool that has enabled the development of novel high-throughput screening and experimentation methods for decades. SAMDI-MS works by immobilizing analytes to functionalized SAMs prior to MS analysis and is capable of...
Genetic studies have found variants in the protein-degrading autophagy-lysosomal pathway (ALP) to be among the most common risk factors for developing Parkinson’s disease (PD). Macroautophagy (MA) is the arm of this pathway which delivers cytosolic components to lysosomes for degradation and is essential for neuronal health. The defining pathological protein...
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...
Methanotrophs, bacteria that can metabolize methane, remain a promising solution to mitigating the effects of climate change by removing atmospheric methane and converting it to useful chemical precursors. However, a full understanding of the main enzyme they use to oxidize methane, particulate methane monooxygenase (pMMO), is critical for harnessing their...
The treatment of AML remains to be a challenge due to the high rates of resistance and relapse experienced by patients after initial therapy. The MAPK-interacting kinases 1 and 2 (MNK1/2) have generated increasing interest as therapeutic targets for AML due to their critical role in malignant hematopoietic transformation via...
Heat shock factor 1 (HSF1) is well known for its role in the heat shock response (HSR), where it drives a transcriptional program comprising heat shock protein (HSP) genes, and in tumorigenesis, where it drives a program comprising HSPs and many noncanonical target genes that support malignancy. Here, we find...
Transfer of information across membranes is fundamental to the function of all organisms and is primarily initiated by transmembrane receptors. This is an allosteric process and involves conformational coupling between ligand-binding domain and signaling domain of a receptor. This allosteric mechanism of activation is unclear for many receptors. Moreover, for...
MYC regulates multiple gene programs, raising questions about the potential selectivity and downstream transcriptional consequences of MYC inhibitors as cancer therapeutics. MYC func-tions to either globally amplify RNA production or selectively regulates genes by repression or ac-tivation. In models of MYC inhibition by small molecules the functionality of MYC is...
Breakthroughs in large-scale biological data collection have resulted in a wealth of -omics (genomics, metabolomics, etc.) datasets in the literature. However, the development of appropriate computational techniques for their analysis is lacking, yet crucial for fully extracting the rich information contained in these datasets. The work in this dissertation describes...