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”...
Promyelocytic leukemia (PML) nuclear bodies act as quality control centers in the nucleus, participating in a plethora of nuclear functions. As such, PML bodies are a signature model for functional nuclear organization. PML bodies have a dynamic protein composition that responds to changing conditions of the cell. Many of the...
T cells and cancer cells have many common features, including their need to proliferate and their metabolic requirements. In particular, glucose metabolism is highly upregulated in both cancer cells and T cells to support proliferation and other cellular functions. The first step of glycolysis is catalyzed by Hexokinase, which exists...
NSD2, a histone methyltransferase specific for methylation of histone 3 lysine 36 (H3K36), exhibits a glutamic acid to lysine mutation at residue 1099 (E1099K) in childhood acute lymphocytic leukemia (ALL). Cells harboring this mutation can become the predominant clone in relapsing disease. We studied the effects of this mutant enzyme...
Inter-organelle contacts facilitate communication between organelles and impact fundamental cellular functions. Investigations into the molecular mechanisms of inter-organelle tethering are still in the early stages, and we are just beginning to appreciate the number and variety of inter-organelle tethers that exist. We have used budding yeast as a model polarized...
Type I interferon (IFN) is the primary antiviral cytokine establishing a broad and potent antiviral response to protect mammalian cells from virus infection. The functional repertoire of IFN extends to innate and adaptive immunity, neoplastic transformation, resistance and cancer immunotherapy. IFN functions are primarily mediated through the Janus kinase (JAK)...
The cellular innate immune response to viruses is a defense mechanism executed by most cells in the human body to form the initial barrier to virus replication. Detection of viral nucleic acids initiates widespread gene expression changes that combine to establish an antiviral state and stimulate professional immune cell activation....
Glioblastoma (GBM) is a highly malignant brain tumor that accounts for the most commonly diagnosed type of primary brain tumors in adults. It has a poor prognosis of only 15 months from the time of diagnosis. The gold standard therapy regimen consists of radiotherapy and the chemotherapeutic temozolomide. Both of...