The microtubule (MT) network and associated regulatory proteins play a critical role during viral infection from facilitating viral particle transport towards the nucleus upon entry to later mediating virion assembly and egress. Many of the precise mechanisms by which viruses commandeer the host MT network to propagate infection remain poorly...
Natural Killer (NK) cell dysfunction is associated with poorer clinical outcome in cancer patients. What regulates NK cell dysfunction in tumor microenvironment is not well understood. NKG2D/NKG2DL pathway is very well recognized as an effective immune axis in tumor immunosurveillance. Abundant evidence from experimental preclinical animal models as well as...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron (MN) degeneration and resulting in progressive paralysis and death. ALS is genetically heterogeneous, disease pathophysiology is not completely understood, and there are no effective drug therapies. To develop broadly applicable therapeutics, we examine disease mechanisms in the...
Mitochondria-lysosome contacts are recently identified sites for mediating crosstalk between both organelles, but their role in normal and diseased human neurons remains unknown. We used super-resolution and live-cell microscopy in human iPSC-derived neurons to demonstrate that mitochondria-lysosome contacts can dynamically form in the soma, axons, and dendrites of human neurons,...
When a collection of individual units behave synchronously, it is often useful to describe the actions of the group. Broadly speaking in Physics, individuals are described as particles and collective actions are described using waves. However, the dynamic symphony of life ordains that orchestral sections play in harmony for a...
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...
Levels of the several different human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) cytidine deaminases vary across different cell types. While levels of nuclear-localized A3s are low or non-existent in primary cells, a nuclear A3 is often upregulated in cancer cells. Increased chromosomal mutagenesis due to nuclear A3...
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;...
Iron is an essential nutrient and is critical for cellular growth and metabolism. Here, we delineate a novel mechanism by which iron alters amino acid homeostasis and mTOR activity by remodeling the cellular epigenetic landscape. We find that iron deficiency inactivates Jumonji-C domain containing histone-demethylases, resulting in histone hyper-methylation and...
Desmosomes, complex structures found at intercellular junctions, are important for the development, structural integrity, and immune barrier of the skin. Extracellular components of the desmosome connect neighboring cells and intracellular interactions amongst cadherin, armadillo, and plakin proteins anchor the desmosome to intermediate filaments. Beyond their canonical role as “spot welds”...
