The NLRP3 inflammasome is a multi-protein complex that drives sterile and pathogen-dependent inflammation. Activation of the NLRP3 inflammasome occurs in two steps: priming and activation. Priming occurs in response to an inflammatory stimulus, such as LPS. LPS-primed macrophages are subsequently activated by a second stimuli, most of which require K+...
A prominent cause of premature ovarian insufficiency (POI) is gonadotoxic cancer therapies, which deplete the ovarian reserve of follicles, oocytes, and hormone-producing cells. Current fertility preservation methods include the removal and cryopreservation of ovarian tissue prior to gonadotoxic treatment. This cryopreserved tissue can be transplanted back and has been found...
Androgen receptor pathway inhibitors are the mainstay treatment for advanced prostate cancer, but resistance is common. Here, we used a CRISPR activation screen to identify genes that promote enzalutamide resistance in the metastatic castration-sensitive prostate cancer cell line LNCaP. We found that activation of the TGF-β target gene, PRRX2, promoted...
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...
Inter-organelle contact sites have become increasingly appreciated as important regulators of cellular homeostasis, and disruption of inter-organelle contact site dynamics and function has been observed in various pathologies. Recently, inter-organelle contact sites between mitochondria and lysosomes were discovered, offering a new mechanism by which these two organelles may directly interact,...
Meiosis is a highly regulated process necessary for proper chromosome division. Zincfluxes regulate mammalian meiosis; between prophase I and metaphase II, total intracellular zinc
increases by 50%, while 20% of zinc is released in “zinc sparks” following fertilization. Although
zinc fluxes had been shown to be conserved in mammals, it...
Gold nanoparticles (AuNPs) display unique characteristics compared to their macro-counterparts that are dependent on shape, size, and attached surface molecules. Methods have been developed to precisely control both size and shape of AuNPs for specific applications. The biocompatibility, plasmonic properties, and ease of functionalization with thiolated molecules, make gold nanoparticles...
A central question in biology is how the flow of genetic information—from DNA to RNA to protein—is regulated. Regulatory mechanisms exerted at the level of DNA and protein have been described in detail but by contrast, little is known regarding the regulation of RNA. Methylation on N6-adenosine (m6A) is the...
The BCR-ABL negative Myeloproliferative Neoplasms (MPNs) are clonal hematopoietic stem-cell disorders characterized by abnormal proliferation of differentiated myeloid lineages. MPNs include 3 clinically distinct disorders: Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). 95% of MPNs are characterized by driver mutations in Janus Kinase 2 (JAK2), Thrombopoietin receptor...
Mitochondrial complex I is the primary entry point for electrons into the mitochondrial electron transport chain that is composed of 45 individual protein subunits that are encoded in both the nuclear and mitochondrial genomes. Mitochondrial complex I sits at an important nexus in the essential bioenergetic, biosynthetic, and signaling functions...