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...
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...
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...
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...
Individuals within a species vary in complex phenotypes, such as responses to toxins. This drug-response variation causes patients who are treated with the same medicine to experience a range of side effects, ultimately decreasing the efficacy of some drugs. Particular genetic variants among individuals might contribute to differential drug responses,...
The epidemic of obesity and associated metabolic diseases have led to increased scrutiny of adipose tissue and its primary cell type, the adipocyte. However, studies show that regional adipose tissue distribution rather than obesity per se is a major determinant of metabolic disease risk. Despite having an obese body mass...
Inter-organelle contacts facilitate communication between organelles and impact fundamental cellular functions. Investigations into the molecular mechanisms of inter-organelle tethering are still in the early stages, and we are just beginning to appreciate the number and variety of inter-organelle tethers that exist. We have used budding yeast as a model polarized...
When a cell divides, it must assemble a microtubule-based structure called a spindle, which provides the forces that physically segregate the chromosomes. In most cell types the microtubules that comprise the spindle are nucleated and organized by centriole-containing centrosomes. In many species, however, oocyte meiosis is carried out in the...
The literature has established glucokinase (GCK) to be the principal hexokinase (HK) in the liver, operating as a glucose sensor to regulate glucose metabolism and lipid homeostasis. We have recently proposed Hexokinase Domain Containing-1 (HKDC1) to be a novel 5th HK with expression in the liver. Here, we reveal HKDC1...