The purpose of my thesis research has been to understand the formation of mitotic chromosome structure by using chromosome micromanipulation. Folding mitotic chromosomes from their loose interphase form into their individualized, compacted form is required for easy handling of the chromosomes for cell division. This process is facilitated by several...
Protein homeostasis, or proteostasis, is essential for preserving all cellular functions and involves a balance of protein synthesis, folding, trafficking, and degradation. A collapse in proteostasis is a common feature of many neurodegenerative disorders that are characterized by the accumulation of insoluble protein aggregates in the brain. Parkinson’s disease (PD)...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Chemotherapy regimens show high response rates but have debilitating effects and carry risk of relapse. Until now, no targeted therapy has been approved. In addition, 40% of patients will relapse and their treatment options are limited because...
Parasitic nematode infections are common in both humans and livestock populations around the globe. In humans, these infections cause illness which can be debilitating. In livestock, parasitic nematode infections result in poor animal health and wellbeing as well as decreases in the yield of these animals. The decrease in yield...
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...
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,...
Symbiotic relationships involve a life-long interaction between host and bacteria, and there is much we do not understand about how these interactions are developed and maintained. During the horizontal recruitment of beneficial bacteria by hosts, a complex set of molecular signals and communication ensures specificity. On the bacterial side, these...
Cytokines made by macrophages play a critical role in determining the course of Legionella pneumophila infection. Prior, murine-based modeling indicated that the cytokine response initiated upon recognition of L. pneumophila involves a subset of Toll-like receptors, namely TLR2, TLR5, and TLR9. Using shRNA/siRNA knockdowns and subsequently CRISPR/Cas9 knockouts (KO), I...
In nearly all Eukaryotes, the membrane-enclosed nucleus contains the vast majority of the cellular genome. Within this sub-cellular compartment, the nuclear architecture facilitates genomic chromatin organization. Controlling chromosomal loci’s spatial positioning relative to subnuclear structures and each other can have local and global effects on gene expression. Moreover, chromatin organization...