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+...
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...
This dissertation focuses on the development of quantitative approaches for characterizing endogenous signaling pathways and designing new pathways in mammalian cells. I demonstrate how mathematical descriptions that are formulated to explain gene expression patterns can also serve as a powerful springboard for deeper analyses into the properties and functions of...
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...
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...
The orderly process of hematopoietic differentiation is governed in large part by the coordinated transcription of specific genes. Deregulation of normal differentiation processes can lead to disease states including immunodeficiency, autoimmune disease, and leukemia. This research focuses on the family of transcription factors known as the early growth response (Egr)...