Posted on | CategoriesHealth and Disease / Oncological Sciences | PI: Bradley R. Cairns, PhD

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
Posted on | CategoriesGenomics / Human Genetics / Pathology | PI: Robert Schlaberg, MD , Gabor Marth, DSc , Mark Yandell, PhD & Karen Eilbeck, PhD

Rapid Identification of Microbial Pathogens

The rapid identification of microbial pathogens is critical for timely and successful treatments. Improved capabilities in pathogen identification were the focus of a collaboration between physicians and scientists in the departments of Biomedical Informatics, Human Genetics, and Pathology. Continue reading → Rapid Identification of Microbial Pathogens
Posted on | CategoriesHealth and Disease / Neurology | PI: Stefan M. Pulst, MD & Daniel R. Scoles, PhD

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
Posted on | CategoriesCancer / Oncological Sciences | PI: Jody Rosenblatt, PhD

Maintaining Epithelial Barriers

A vital issue in cell biology is how epithelial sheets provide a barrier while balancing cell growth and death, and withstand the stretching forces that sheets experience in vivo. Rosenblatt and colleagues demonstrated that mechanical stretching stimulates epithelial cell division and characterized the stretch-sensitive Piezo1 channel as well as the downstream signaling that triggers cell division. Continue reading → Maintaining Epithelial Barriers
Posted on | CategoriesCancer / Oncological Sciences | PI: Trudy G. Oliver, PhD

Defining Pathways for Formation and Suppression of Highly Metastatic Lung Tumors

Cancers arise from the complex interplay of oncogene activation and tumor suppressor inactivation. Oliver and colleagues uncovered how Myc cooperates with other oncogene products to promote aggressive, highly metastatic lung tumors. Continue reading → Defining Pathways for Formation and Suppression of Highly Metastatic Lung Tumors
Posted on | CategoriesImmunology, Inflammation, Infectious Disease / Pediatrics | PI: Christian Con Yost, MD , Guy A. Zimmerman, MD & Elizabeth A. Middleton, MD

Inhibiting Neutrophil Extracellular Traps (NETs) in Immune Injury and Pathologic Clotting

Deficient or excess immune system activities cause many human diseases. To understand the mechanisms of immune injury and their links to pathologic clotting, University of Utah Health investigators Christian Yost, MD, Guy Zimmerman, MD, and colleagues defined features of neutrophil extracellular traps (NETs). Continue reading → Inhibiting Neutrophil Extracellular Traps (NETs) in Immune Injury and Pathologic Clotting
Posted on | CategoriesPediatrics / Prevention | PI: Julie H. Shakib, DO

Translating Influenza Immunization in Pregnancy into Infant Immunity

Infants with influenza are at increased risk for adverse outcomes, particularly in the first six months when they are unable to mount a sufficient response to influenza immunization. Few large-scale studies have evaluated the impact of maternal immunization during pregnancy on subsequent infant influenza outcomes. To address this gap, Julie Shakib, DO, and colleagues conducted a retrospective cohort study of 245,386 pregnant women and their infants over nine influenza seasons. They found that infants born to women reporting influenza immunization during pregnancy had risk reductions of 70% for influenza infection and 81% for influenza hospitalization in the first six months. Continue reading → Translating Influenza Immunization in Pregnancy into Infant Immunity
Posted on | CategoriesImmunology, Inflammation, Infectious Disease / Internal Medicine | PI: Andrew S. Weyrich, PhD

The Power of mRNA in Anucleate Platelets

Andrew Weyrich, MD, and his group made the seminal discovery that anucleate human platelets transform messenger RNA (mRNA) into mature products that code for protein. More recently, his group found that a specific type of microRNAs (Dicer1-dependent) and their precursors (megakaryocytes) modulate the expression of target mRNAs important for cellular function. Continue reading → The Power of mRNA in Anucleate Platelets
Posted on | CategoriesHealth and Disease / Internal Medicine | PI: Tianxin Yang, MD, PhD

(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
Posted on | CategoriesBiochemistry / Fundamental Biology | PI: Wesley I. Sundquist, PhD & Adam Frost, PhD

Cellular Membrane Remodeling

Cells are continually severing, fusing, and reshaping their membranes. One of the essential cellular membrane remodeling systems is the ESCRT (Endosomal Sorting Complexes Required for Transport) pathway, whose cellular functions include endosomal membrane remodeling, membrane repair, enveloped virus budding, closure of the nuclear envelope, and cytokinetic abscission. Continue reading → Cellular Membrane Remodeling
Posted on | CategoriesCardiovascular / Internal Medicine | PI: Alfred Cheung, MD

Blood Pressure Treatment Target

Researchers have long debated the optimal blood pressure for people older than age 50, especially in older adults who might not tolerate lower blood pressure. Alfred Cheung, MD, and colleagues at University of Utah Health led one of five national Clinical Center Networks to design and conduct the Systolic Blood Pressure Intervention Trial (SPRINT). Continue reading → Blood Pressure Treatment Target
Posted on | CategoriesGenomics / Internal Medicine | PI: Corrine K. Welt, MD

Genetic Risk for Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is characterized by excessive androgen hormone, irregular menstrual cycles, and polycystic ovaries on ultrasound. Affected women also frequently experience metabolic disturbances, including obesity, and face increased risk for type 2 diabetes. University of Utah Health investigator Corrine Welt, MD, and collaborators performed an international meta-analysis of whole genome association studies combining over 10 million genetic markers in more than 10,000 European women with PCOS and 100,000 controls. Continue reading → Genetic Risk for Polycystic Ovary Syndrome
Posted on | CategoriesHealth and Disease / Psychiatry | PI: Adrian Rothenfluh, PhD

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
Posted on | CategoriesCancer / Neurosurgery | PI: Howard Colman, MD, PhD , Adam L. Cohen, MD & Sheri L. Holmen, PhD

The Role of IDH Mutation in Human Brain Tumors

Sheri Holmen, PhD, was the first to show that IDH mutations, on the appropriate genetic background, resulted in glioma initiation and growth. This discovery provided the basis of a pre-clinical model for testing the contribution of other molecular alterations to the pathogenesis of, and the effects of various treatments on, these tumors. Howard Colman, MD, PhD, and colleagues subsequently demonstrated that increased DNA alterations were associated with higher-grade gliomas and worse prognoses. Continue reading → The Role of IDH Mutation in Human Brain Tumors
Posted on | CategoriesHealth and Disease / Pediatrics | PI: J. Michael Dean, MD

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
Posted on | CategoriesPrevention / Surgery | PI: Benjamin Brooke, MD

Readmission Destination and the Risk of Mortality Following Major Surgery

University of Utah Health investigator Benjamin Brooke, MD, PhD, and colleagues sought to determine whether patients who are readmitted following major surgery achieve better outcomes if they return to the same hospital and surgeons who performed their initial operation. Continue reading → Readmission Destination and the Risk of Mortality Following Major Surgery