Pathogenic bacteria scavenge essential nutrients including metals, amino acids and peptides to survive within the hostile host environment. Bacteria utilize ATP-binding cassette (ABC) transporters, powered by the energy of ATP hydrolysis, to move substrates across cellular membranes. The substrate-binding protein (SBP) shuttles substrate in the periplasm and directs the substrate...
The ribosome, the cell’s machine for synthesizing proteins, can be thought of as the chef of the cell. Just as a chef reads a recipe and combines ingredients to create a dish, the ribosome reads cellular instructions and connects building block molecules (amino acids) to construct proteins. Like the final...
Burkitt lymphoma (BL) is a B cell cancer that develops primarily in children and is associated with Epstein-Barr virus (EBV). The EBV latent membrane protein 2A (LMP2A) drives BL in part by providing constitutively active pro-survival signaling. A double transgenic mouse model of BL expressing LMP2A and the oncogene MYC...
Store-operated Ca2+ entry through Orai1 channels mediate transcriptional, proliferative, and effector cell programs in many cells and are activated through a unique inside-out mechanism involving binding of the endoplasmic reticulum Ca2+ sensor, STIM1, to cytoplasmic sites on Orai1. Mutations in Orai1 that block channel activation or evoke constitutive channel activity...
The critical importance of alternative mRNA splicing and the RNA binding proteins that orchestrate this essential layer of post-transcriptional gene regulation is increasingly recognized in gene regulatory programs. We and others have shown that alternative splicing plays a causal role during the Epithelial-Mesenchymal transition, a cell-developmental program that is hijacked...
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+...
Nanocarriers are nanometer-sized (1-1000 nm) structures capable of encapsulating cargo. This encapsulation can drastically alter the pharmacokinetic properties of the cargo, while also allowing for the rational design and engineering of the nanocarrier itself. Poly(ethylene glycol)-block-poly(propylene sulfide) is an amphiphilic diblock copolymer capable of self-assembling into diverse nanocarriers. The purpose...
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...
A variety of human diseases and pregnancy related disorders reflect endometrial dysfunction. However, rodent models do not share fundamental biological processes with the human endometrium, such as cyclic menstruation, and no existing human cell cultures recapitulate the cyclic interactions between endometrial stromal and epithelial compartments necessary for decidualization and implantation....
Proper size control of organs and tissues is critical to their function, and it is necessary for the millions of precisely sized tubes that make up those organs— for example, excessive cell growth can lead to devastating diseases such as Polycystic Kidney Disease. The regulation of tube growth is therefore...