The Bcl-2 family is considered the guardian of the mitochondrial apoptotic pathway. While there are numerous endogenous Bcl-2 antagonists that share similar homology, structure, topology, and expression pattern, only the loss of Bim in mice is sufficient to lead to the development of a systemic autoimmunity. Even loss of both...
The Pseudomonas aeruginosa type III secretion system delivers effector proteins directly into target cells, allowing the bacterium to modulate host cell functions. ExoU is the most cytotoxic of the known effector proteins and has been associated with more severe infections in humans. Previous studies have shown that ExoU is a...
MAPK-interacting kinase (MNK) signaling leads to activation of cap-dependent mRNA translation through phosphorylation of the eukaryotic translation initiation factor 4E (eIF4E). In cancer cells, MNK-eIF4E signaling promotes translation of oncogenic mRNAs. In glioblastoma (GBM), the deadliest malignant brain tumor, MNK-eIF4E signaling is aberrantly activated and represents a promising therapeutic target....
The development of targeted therapies has revolutionized cancer treatment and markedly increased patient survival time and reduced mortality rates. Yet, some cancers still have few treatment options and remain deadly. In these cases, the development of targeted therapy is critical. Here, we investigated two cancers that lack effective targeted therapies...
Spindle formation in mammalian cells requires precise spatial and temporal regulation of the kinesin-5 motor proteins which generate outward force to establish spindle bipolarity. A growing body of work suggests that phosphorylation of kinesin-5 motor domains is an important regulator of their motor characteristics and function in cells. My thesis...
Efferocytosis is the anti-inflammatory removal of dying cells and cellular debris, occurring billions of times per person, per day as a part of homeostatic maintenance during natural cell turnover. Macrophages are major professional phagocytes of the immune system and are responsible for dead cell clearance during infection and injury. During...
A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). Due to the low polymorphism of MHC Ib molecules within the human population, these molecules and Mtb antigens are attractive targets for better vaccine development. Among these, HLA-E...
Metabolic abnormalities of cancers provide opportunities for novel tumor-specific therapies. Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (αKG) and the reduction of NAD(P)+ to NAD(P)H. Oncogenic mutations in two IDH-encoding genes (IDH1 and IDH2) have been identified in acute myelogenous leukemia, low-grade glioma, and secondary glioblastoma...
Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection gonorrhea and is adapted to survive in humans, its only host. The N. gonorrhoeae cell wall is critical for maintaining envelope integrity, resisting immune cell killing, and production of cytotoxic peptidoglycan (PG) fragments. Deletion of the N. gonorrhoeae genes...
The hormone prolactin (PRL) contributes to breast cancer pathogenesis through various signaling pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL-induced activation of the transcription factor STAT5 results in the upregulation of numerous genes implicated in breast cancer pathogenesis. However, the...