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...
One of the fundamental observations in oncology is that the rate of cancer malignancy increases with age, which applies to most human malignancies including breast cancer. Therefore, it is crucial to elucidate the mechanistic connection between aging and carcinogenesis. The NAD+-dependent sirtuin family, specifically SIRT3, the primary mitochondrial deacetylase, which...
Some of the oldest drugs targeting metabolism are the antifolates such as aminopterin and methotrexate (MTX). MTX started being used in the 1950s to treat rheumatoid arthritis. Aminopterin and MTX both target one carbon metabolism and inhibit proliferation of cells. MTX was a potent inhibitor of inflammation, because it prevented...
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...
Macrophages are one of the most versatile immune cells in the immune system. They are found in nearly every tissue and organ throughout the body. Macrophages play important roles of orchestrating initiation and resolution of inflammation, such as sentineling against pathogens or engulfing apoptotic cells. Macrophages are able to respond...
Recent advances in cell-free synthetic biology have spurred the development of in vitro molecular diagnostics that serve as effective alternatives to whole-cell biosensors. However, cell-free sensors for detecting manmade organic water contaminants such as pesticides are sparse, partially because few characterized natural biological sensors can directly detect such pollutants. Here,...
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...
Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, met-abolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol...