Published in Annual Review of Pharmacology and Toxicology
My research activity started with studies on drug metabolism in rat liver microsomes in the early 1960s. The CO-binding pigment (cytochrome P450) had been discovered a few years earlier and was subsequently found to be involved in steroid hydroxylation in adrenal cortex microsomes. Our early studies suggested that it also participated in the oxidat...
Published in Annual Review of Pharmacology and Toxicology
The transcription factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) is a central regulator of redox, metabolic, and protein homeostasis that intersects with many other signaling cascades. Although the understanding of the complex nature of NRF2 signaling continues to grow, there is only one therapeutic targeting NRF2 for clinical us...
Published in Annual Review of Pharmacology and Toxicology
Type 2 diabetes (T2D) is characterized by persistent hyperglycemia despite hyperinsulinemia, affects more than 400 million people worldwide, and is a major cause of morbidity and mortality. Insulin resistance, of which ectopic lipid accumulation in the liver [nonalcoholic fatty liver disease (NAFLD)] and skeletal muscle is the root cause,...
Published in Annual Review of Pharmacology and Toxicology
Efflux mechanisms situated in various brain barrier interfaces control drug entry into the adult brain; this review considers the effectiveness of these protective mechanisms in the embryo, fetus, and newborn brain. The longstanding belief that the blood-brain barrier is absent or immature in the fetus and newborn has led to many misleading stateme...
Published in Annual Review of Pharmacology and Toxicology
Thyroid-associated ophthalmopathy (TAO), the ocular manifestation of Graves’ disease, is a process in which orbital connective tissues and extraocular muscles undergo inflammation and remodeling. The condition seems to result from autoimmune responses to antigens shared by the thyroid and orbit. The thyrotropin receptor (TSHR), expressed at low lev...
Published in Annual Review of Pharmacology and Toxicology
Hypoxia-inducible factors (HIFs) control transcriptional responses to reduced O2 availability. HIFs are heterodimeric proteins composed of an O2-regulated HIF-α subunit and a constitutively expressed HIF-1β subunit. HIF-α subunits are subject to prolyl hydroxylation, which targets the proteins for degradation under normoxic conditions. Small molecu...
Published in Annual Review of Pharmacology and Toxicology
Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNA decoys, DNAzymes, synthetic guide strands for CRISPR/C...
Published in Annual Review of Fluid Mechanics
Fungi are the dark matter of biology, typically leading cryptic lives, buried in soil or inside of plants or other organisms, and emerging into the light only when they build their elegantly engineered fruiting bodies. Ecological success across so many niches has required that they solve many challenging fluid mechanical problems of growth, dispers...
Published in Annual Review of Fluid Mechanics
The 1969 review by J.R. Melcher and G.I. Taylor defined the field of electrohydrodynamics. Fifty years on, the interaction of weakly conducting (leaky dielectric) fluids with electric fields continues to yield intriguing phenomena. The prototypical system of a drop in a uniform electric field has revealed remarkable dynamics in strong electric fiel...
Published in Annual Review of Fluid Mechanics
Modeling wall turbulence remains a major challenge, as a sufficient physical understanding of these flows is still lacking. In an effort to move toward a physics-based model, A.A. Townsend introduced the hypothesis that the dominant energy-containing motions in wall turbulence are due to large eddies attached to the wall. From this simple hypothesi...
