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,...
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...
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...
Dysfunction in mitochondrial dynamics is believed to contribute to a host of neurological disorders and has recently been implicated in cancer metastasis. The outer mitochondrial membrane adapter proteins Miro1 and Miro2 play a role in the regulation of mitochondria. Each paralog comprises two GTPase domains flanking two centrally located calcium/magnesium-binding...
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...
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...
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;...
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...