Reconstituting HIV Replication in a Test Tube

Reverse transcription and integration are key events in retrovirus replication and are also targets of successful anti-HIV therapies. Reverse transcription creates a double-stranded DNA copy of the viral RNA genome, and integration archives that copy within the genome of the infected cell. However, studies of the mechanisms underlying these steps of the viral life cycle remain challenging because these processes are performed by viral core particles located deep within the infected cell cytoplasm and nucleus. Continue reading → Reconstituting HIV Replication in a Test Tube

Megakaryocytes and Platelets in Immune and Inflammatory Responses and in COVID-19

Platelets—small cells which circulate in abundance in the bloodstream—are traditionally known for their ability to form clots and stop bleeding. Recent studies, however, have shown that platelets and their parent cells, megakaryocytes, also play a role in inflammation and infection. University of Utah Health investigators Robert Campbell, PhD, and Matthew Rondina, MD, and colleagues discovered that platelets and megakaryocytes respond robustly to infection, including COVID-19. These infection-driven changes in platelets activate clotting mechanisms and thus may contribute to the blood clots that complicate COVID-19 infection. Continue reading → Megakaryocytes and Platelets in Immune and Inflammatory Responses and in COVID-19

Visualizing the SARS-CoV-2 Life Cycle

SARS-CoV-2 is defining disease of the current era. Many biological researchers have redirected their focus to understanding and defeating the virus, rapidly leading to new insights into how the virus gains access to and hijacks human cells. University of Utah Health investigator Janet Iwasa, PhD, and colleagues have used this information to create detailed molecular animations of different stages of the SARS-CoV-2 life cycle. Continue reading → Visualizing the SARS-CoV-2 Life Cycle

A Potent, Long-lasting HIV Capsid Inhibitor

Reverse transcription and integration are key events in retrovirus replication and are also targets of successful anti-HIV therapies. Reverse transcription creates a double-stranded DNA copy of the viral RNA genome, and integration archives that copy within the genome of the infected cell. However, studies of the mechanisms underlying these steps of the viral life cycle remain challenging because these processes are performed by viral core particles located deep within the infected cell cytoplasm and nucleus. Continue reading → A Potent, Long-lasting HIV Capsid Inhibitor

Supporting Health by Screening for Social Needs

When patients struggle to get enough food, lack stable housing, or have limited access to transportation, their health can suffer. One analysis estimated that as much as 50 percent of the variation in health outcomes between counties in the U.S. can be attributed to social determinants of health like these. Such factors can limit the … […] Continue reading → Supporting Health by Screening for Social Needs Continue reading → Supporting Health by Screening for Social Needs

Continue reading → Supporting Health by Screening for Social Needs

Neuronal Connections in the Retina

Bryan Jones, PhD, and colleagues used electron microscopes to visualize the chemical and electrical synaptic connections that makes up the neural network. They further observed, in a transgenic rabbit model of early retinal degeneration, abnormal connectivity in the rod-photoreceptor network and novel synaptic connections derived from sprouting. Continue reading → Neuronal Connections in the Retina

Unexpected Antiviral Activity of Spironolactone

Epstein–Barr virus (EBV) is a human herpesvirus associated with clinical infections and several types of malignancies. Sankar Swaminathan, MD, and colleagues showed that a hypertension/heart failure drug, spironolactone, also has anti-EBV effects. Continue reading → Unexpected Antiviral Activity of Spironolactone

New Class of Therapy for Chronic Heart Failure

The lab directed by Robin Shaw (MD, PhD) and Nora Eccles Harrison Cardiovascular Research & Training Institute (CVRTI) Investigators have identified an architectural protein (cBIN1) of heart muscle cells that organizes the intracellular signalizing network responsible for heart muscle contraction and relaxation. Continue reading → New Class of Therapy for Chronic Heart Failure

A Rapidly Manufacturable, Open-Source Ventilator for Austere Conditions

At the beginning of the COVID-19 pandemic, severe ventilator shortages led to dire situations both in developed regions and in low-resource regions where robust and affordable ventilators were already scarce. To address this urgent need, University of Utah Health researcher Kai Kuck, PhD, and colleagues developed Pufferfish, a complete intensive care unit ventilator capable of supporting the continuum from noninvasive ventilation to full mechanical ventilation. Continue reading → A Rapidly Manufacturable, Open-Source Ventilator for Austere Conditions

Enhancing Decision-making for Diagnosis and Management of Respiratory Infection

Barbara Jones, MD, and Matthew Samore, MD, used national data from the Department of Veterans Affairs to examine decision-making and practice patterns among providers prescribing antibiotics for patients diagnosed with acute respiratory infection. Continue reading → Enhancing Decision-making for Diagnosis and Management of Respiratory Infection

Lipid Metabolism and Cardiometabolic Disease

Metabolic diseases such as diabetes, steatohepatitis, and coronary artery disease result from the delivery of nutrients that exceed a tissue’s energetic needs or storage capacity. The excess nutrients give rise to deleterious lipid species that impair cellular function. Summers and colleagues found that ceramides, a class of sphingolipids, alter the metabolism of liver and adipose tissue in a way that gives rise to cardiometabolic disease. Continue reading → Lipid Metabolism and Cardiometabolic Disease

How Cells Choose to Create Energy

To supply their energy needs, cells typically choose between utilizing glucose in the cytoplasm (aerobic glycolysis and lactic acid fermentation) or “burning” pyruvate in the mitochondria (mitochondrial carbohydrate oxidation). Although this is arguably the most fundamental metabolic decision that cells make, before 2012 it was not clear how cells import pyruvate into mitochondria to fuel ATP production. Continue reading → How Cells Choose to Create Energy

How Iron Deficiency Impairs Pancreatic β-Cell Function

Research in the lab of Elizabeth Leibold, PhD, showed that in mice with iron deficiency, proinsulin processing to mature insulin was impaired, resulting in reduced levels of circulating and glucose intolerance. Mice treated with iron restored insulin to normal levels and eliminated the glucose intolerance. Continue reading → How Iron Deficiency Impairs Pancreatic β-Cell Function

Mechanisms of Circulatory Abnormalities and Fatigue in Patients with Cardiovascular Diseases

Markus Amann, PhD, and colleagues recently discovered that both heart failure and hypertension impair an important neurocirculatory control mechanism in humans—specifically, a reflex loop mediated by neural feedback from muscles to the central nervous system. This impairment results in excessive sympathetic nervous system activity, and largely accounts for the circulatory abnormalities observed during physical activities. Continue reading → Mechanisms of Circulatory Abnormalities and Fatigue in Patients with Cardiovascular Diseases

Architecture of the Inner Ear

Normal hearing is dependent upon a highly specialized structure in the inner ear called the tectorial membrane. How this precisely organized extracellular matrix is assembled had been unknown. However, Park and colleagues showed the inner ear membrane anchors to the cell surface during development and grows one layer at a time. Continue reading → Architecture of the Inner Ear

Gene Expression and Health Risks

An important area of research involves learning how gene expression influences health and disease risks. The parts of the genome that regulate gene expression are cis-regulatory elements. Gregg and colleagues took an unusual approach to discover these cis-regulatory elements by analyzing the genomes of species that evolved disease resistance “superpowers”. Continue reading → Gene Expression and Health Risks

How Microbes Make Drug-like Molecules

Many life-saving drugs come from natural sources such as microbes. Learning how host organisms produce these drugs is an area of intense interest because scientists could exploit the pathways to produce more and better drug variants. Schmidt and colleagues have elucidated the mechanisms by which microbes produce one class of drug-like molecules, the Ribosomally-synthesized and Post-translationally modified Peptides (RiPPs). Continue reading → How Microbes Make Drug-like Molecules

An EHR Clinical Support App for Monitoring Bilirubin Levels

Electronic health records (EHR) are a rich source of clinical and research data, but clinicians and researchers often cannot access this information efficiently. The Department of Biomedical Informatics has developed the ReImagineEHR initiative to improve the functionality of electronic health record systems. Continue reading → An EHR Clinical Support App for Monitoring Bilirubin Levels

Drug-Free Macromolecular Therapeutics

Monoclonal antibody therapy has numerous benefits but can lack efficacy, often because monovalent binding of antibodies to specific receptors fails to translate into an active response. The Kopeček laboratory has built on their track record in polymeric drug delivery to develop a novel approach to therapeutic design, termed “Drug-Free Macromolecular Therapeutics (DFMT)”. Continue reading → Drug-Free Macromolecular Therapeutics

Bone-Anchored Devices that Permanently Pass Through the Skin to Maximize Amputee Function

A common orthopedic approach to recreating damaged joints is to securely attach a metal implant to the patient’s own bone, a process known as osseointegration. Our research explores a new approach by engineering percutaneous osseointegration devices, in which the metal implant that pass permanently through the skin and permit connection to an external prosthetic limb when desired. The connection can not only be accomplished easily as needed; it also improves the function of the prosthesis. Continue reading → Bone-Anchored Devices that Permanently Pass Through the Skin to Maximize Amputee Function

Analyzing Human Pedigrees to Advance Genetics and Health

Well curated human pedigrees like the iconic pedigrees maintained by the Centre d’Etude du Polymorphism Humain (CEPH) provide an invaluable resource for fundamental discoveries in human genetics and health. The CEPH collection includes families collected by R. White (Utah), J. Dausset (French), J. Gusella (Venezuelan), and J. Egeland (Amish). Continue reading → Analyzing Human Pedigrees to Advance Genetics and Health

Cellular Origins of Pancreatic Cancer

Our pancreas has two main functions, endocrine control of blood sugar and exocrine production of the enzymes that digest our food. These enzymes are synthesized by pancreatic acinar cells and transported to the intestine through a network of pancreatic duct cells. Pancreatic cancer, the third deadliest cancer in the U.S., was previously assumed, based on histology and gene expression, to arise from duct cells. Continue reading → Cellular Origins of Pancreatic Cancer

Biological Consequences of Reduced Energy Flux and Inefficient Energy Generation

Energy transfer processes are never perfectly efficient. Funai and colleagues have discovered that the degree of inefficiency in cellular energy exchange, particularly during oxidative phosphorylation, has important biological implications. Continue reading → Biological Consequences of Reduced Energy Flux and Inefficient Energy Generation