Signaling Pathways That Underlie Heart Disease

Diseases affecting heart function exact an enormous toll on human health, but many of the genetic and molecular mechanisms underlying heart disease remain unknown. Yost and colleagues discovered novel roles for the same developmental signaling pathway in two seemingly unrelated sources of cardiac dysfunction: adult heart failure and embryonic heart malformation. Continue reading → Signaling Pathways That Underlie Heart Disease

Finding New Ways to Treat Kidney Disease

Research in the Kohan lab, using genetically engineered mice, has helped identify the peptide, endothelin-1, and its receptor, ETA, as key regulators of blood pressure and kidney function in health. They have also helped determine that kidney ET-1 production is increased in many kidney diseases and, via activation of ETA receptors on most kidney cell types, leads to inflammation, scarring and decreased kidney function. Continue reading → Finding New Ways to Treat Kidney Disease

Diaphragm Development and Congenital Hernias

The diaphragm is an essential mammalian skeletal muscle, as it is required for respiration and serves as a barrier between the thoracic and abdominal cavities. The Kardon lab used sophisticated mouse genetic studies to establish that the diaphragm arises from multiple embryonic tissues. Continue reading → Diaphragm Development and Congenital Hernias

Structure and Function of the Polycystic Kidney Disease Channel

The kidney senses and responds to physiological changes, such as pH, ionic strength, pressure, and nutrient levels. Sensing is mediated by a coupled sensor/ion channel complex called the Polycystic Kidney Disease Channel, which is composed of two subunits, the PKD1 (the primary sensor) and PKD2 (the channel). Continue reading → Structure and Function of the Polycystic Kidney Disease Channel

Vascular Inflammation in Malaria Pathogenesis

The pathogenesis of malaria is characterized by vascular inflammation exacerbated by immune cells that travel to areas where red blood cells infected with parasites stick to the endothelium lining the blood vessels. The Lamb lab has made significant discoveries demonstrating a key role for receptor tyrosine kinase family Eph receptors in malaria pathogenesis. Continue reading → Vascular Inflammation in Malaria Pathogenesis

ARF6 Plays Key Role in Diabetes-Induced Blindness

University of Utah Health researcher Weiquan Zhu, PhD, and colleagues identified a protein, known as ARF6, which regulates the effects of VEGF by maintaining and amplifying its receptor signaling, thus stimulating a series of cascading responses that lead to diabetic retinal edema. Continue reading → ARF6 Plays Key Role in Diabetes-Induced Blindness

Genes Responsible for Maintaining Embryonic Developmental Potential

A major question concerning early embryos involves how early cleavage-stage (two-cell) embryos establish unlimited developmental potential – termed totipotency. Cairns and colleagues identified the multicopy retrogene, DUX4 in humans or Dux in mice, as a transcription factor that is turned on in very early embryos and activates hundreds of genes and retroviral elements during cleavage stage. Continue reading → Genes Responsible for Maintaining Embryonic Developmental Potential

Therapy for ALS

Amyotrophic lateral sclerosis (ALS) is a catastrophic degeneration of the nervous system with great need for disease-modifying treatments. Stefan Pulst, MD, and his collaborator Daniel Scoles, PhD, were studying a lesser-known but similarly dire condition (spinocerebellar ataxia 2, SCA2) when they identified a gene relevant to both diseases. Continue reading → Therapy for ALS

(Pro)Renin Receptor: A Novel Target for Hypertension, Kidney Disease, and Metabolic Syndrome

The enzyme renin plays a role in the development of hypertension (high blood pressure), cardiovascular disease, and kidney disease. Studies in mice and rats unexpectedly uncovered other biological activities of the receptor for renin and its precursor, (pro)renin receptor (PRR). University of Utah Health researcher Tianxin Yang, MD, PhD, and colleagues have made a series of new discoveries about the function of PRR. They demonstrated that PRR activation stimulates sodium and water retention by the kidney, causing hypertension; over-activation of PRR also causes kidney damage. Targeting this pathway with a compound that blocks PRR is highly effective in treating hypertension and chronic kidney disease in rodents. Continue reading → (Pro)Renin Receptor: A Novel Target for Hypertension, Kidney Disease, and Metabolic Syndrome

Genetics of Alcohol Abuse – from Flies to Humans

In an unbiased screen, the lab directed by Adrian Rothenfluh, PhD, isolated flies lacking a certain gene (Rsu1) that produces a strong liking for alcohol, even before repeated exposure. Their investigations in Drosophila showed that Rsu1 and downstream signaling molecules regulate actin dynamics; genetic manipulations that increase actin filament turnover lead to accelerated development of alcohol preference, while manipulations that increase actin filament stability abolish the development of preference. Continue reading → Genetics of Alcohol Abuse – from Flies to Humans

Lowering Body Temperature After Cardiac Arrest

Hypothermia (lowering the body temperature to subnormal levels) after cardiac arrest became standard practice in adult and neonatal critical care in the early 2000s, but its benefits in children were unknown. To answer this question, University of Utah Health researcher J. Michael Dean, MD, and colleagues conducted two randomized trials (in-hospital and out-of-hospital) at 38 U.S. and international sites, comparing hypothermia with normothermia—maintenance of normal body temperature—after cardiac arrest. Over 4,000 children were screened and 624 participated in the trials. In both trials, researchers found no benefit from hypothermia versus normothermia. Continue reading → Lowering Body Temperature After Cardiac Arrest