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+...
In the United States, allergic disease affects approximately 60 million people and impacts more people every year. While prevalence of allergic disease has steadily increased, there has concurrently been an increase in rates of metabolic syndrome—characterized by increased abdominal girth, decreased sensitivity to insulin, and higher levels of circulating blood...
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...
Skeletal muscle is a highly sexually dimorphic tissue, with males and females exhibiting differences in muscle size, gene transcription, and metabolism. This thesis describes two models wherein males and females responded to an intervention with the same physiological adaptation but through two distinct mechanisms. In the first model, mice of...
Macrophages are innate immune cells that are traditionally thought to be specialists in phagocytosis. More recent evidence suggest that macrophages reside in nearly every organ and readily adapt to local microenvironmental signals, leading to highly plastic phenotypes across and within tissues. Therefore, rather than treating it as a homogenous cell...
Eukaryotic genomes are organized into chromatin, which acts to regulate access to the organism’s genetic material. A large and diverse class of proteins, known as chromatin modifiers and remodelers, are responsible for regulating the composition and structure of chromatin by monitoring nucleosomes. Chromatin remodelers are involved in multiple cellular processes,...
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...
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...
Processing of sensory information in the brain is a pervasive and fundamental phenomenon across animal species and is involved in both "hard-wired" innate responses as well as learned and adaptive behaviors. Here, I show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity and complex processing...