Academics & Research

Research

Driving Discovery

From genetics to geriatrics, pharmacy to pediatrics: University of Utah Health is making discoveries that are pushing the frontiers of science and medicine. Check the Driving Discovery blog and News Room for research highlights.

Gene Linked to Higher Risk for Premature Menopause

While most women experience menopause around 51 years of age, women with primary ovarian insufficiency go through menopause before the age of 40, with some going through the life-altering event as early as in their teens. Corrine Welt, MD, professor of internal medicine at University of Utah Health, believes an answer may lie in the scores of genetic data housed in the Utah Population Database (UPDB).

How Cells Repair the “Bubble Wrap” that Protects DNA

Our DNA is wrapped in a bubble, a double membrane called the nuclear envelope, which protects it and directs molecular traffic to and from the nucleus. Many natural processes, such as cell division, create holes in the nuclear envelope, and for years, scientists have puzzled over how these gaps are filled. New research from the Department of Biochemistry and Department of Oncological Sciences has helped to elucidate this process, finding how an ancient pathway is recruited to do the job.

Relief at Their Fingertips: Phone Monitoring Program Reduces Suffering of Chemotherapy Patients

Patients undergoing chemotherapy often experience difficult but treatable symptoms – including fatigue, pain, and nausea - in between healthcare appointments. But because providers are often not aware of them, some patients undergo unnecessary suffering. A new study by investigators at Huntsman Cancer Institute and the College of Nursing at the University of Utah shows that relief could be just a phone call away.

When it Comes to Preventing Clots, Deviating from Recommended Dosing Could Come with a Cost

For patients affected by atrial fibrillation, a form of irregular heartbeat, increased risk for blood clots and stroke is a serious concern. Medicines used to thin the blood offer a relatively simple treatment that can significantly reduce the risk of clots and strokes. Steinberg and colleagues found that 13 percent of patients did not receive proper dosing of non-vitamin K antagonist oral anticoagulants (NOACs), a specific kind of blood thinner, doubling risk for death in over dosed patients. Compared to patients receiving the appropriate dosage, the risk of death was nearly doubled in over-dosed patients, and under-dosed patients experienced increased rates of hospitalization due to cardiac events.

Oxygen Therapy No Benefit to Patients with Moderate COPD

A randomized trial of people with stable moderate forms of Chronic Obstructive Pulmonary Disease (COPD) concluded that receiving supplemental oxygen therapy made no difference in quality of life, lung function or ability to walk in those who received the therapy compared with those who did not. The study, called the Long-Term Oxygen Treatment Trial Research Group (LOTT), conducted at 42 U.S. medical centers, also found that receiving supplemental oxygen therapy did not delay how soon patients died or were first hospitalized compared with those who didn’t receive oxygen.

Richard E. KannerInternal Medicine, Division of Pulmonology

Gene's Battle with Microbes Promotes Evolutionary Innovation in Humans

The lactoferrin gene arose in early mammals approximately 160 million years ago, and can still be found in the genomes of humans and other primates. New research shows that lactoferrin, whose original function was to transport nutrient metals such as iron, has undergone “rapid” evolution to develop another role – immune defense against microbes that cause potentially deadly diseases of meningitis, pneumonia and sepsis.

Tendon Issues and Rotator Cuff Tears? It's in the Genes

People with rotator cuff tears often experience other tendon or nerve problems as well, but it has been unclear whether those associated ailments are influenced by genetics or environment. New research shows strong evidence that those “global” tendinopathies in the shoulders, knees, hips and other areas appear to cluster among blood relatives and spouses of people with torn rotator cuffs, suggesting that both genetic and environmental factors are involved.

Robert Z. TashjianOrthopaedics

Explaining Variable Signs of Sepsis

In patients with sepsis, the infecting microbes are usually viewed as generic triggers of inflammation while the patients themselves are considered the primary variables that affect disease progression and severity. This viewpoint is challenged by new work published in the April issue of the journal mSphere by researchers in the Department of Pathology at the University of Utah School of Medicine. The study shows that variations in just a single bacterial protein known as flagellin can significantly alter levels of inflammation and the progression of sepsis.

Lower Bicarbonate, Higher Risk for an Early Death

Otherwise healthy older people with low levels of bicarbonate, a major element in the body that helps maintain proper pH balance, were at a 24 percent higher risk of dying prematurely than those in a study group whose bicarbonate levels were normal or even high. Findings from the study suggest that physicians might want to take a closer look at the bicarbonate levels in older patients to identify those at risk for an early death.

Prevention Program Eliminates Bloodstream Infections in Burn Trauma Unit Patients

By implementing a program to prevent bloodstream infections associated with central-line catheters, the University of Utah Health Care Burn Trauma Intensive Care Unit eliminated those hazards entirely, a multidisciplinary committee of the health care system’s nurses and physicians reported in JAMA Surgery. Central-line catheters are inserted into patients’ veins to serve as a main port for delivering medications, antibiotics and other IV fluids, eliminating the need to insert new catheters each time a patient requires fluids or drugs. Such lines, however, can attract germs and lead to bloodstream infections in patients, an especially important issue in burn trauma intensive care units. The prevention program focuses on key elements to prevent central-line infections, such as ensuring that lines are inserted according to federal Agency for Healthcare Research and Quality recommendations, using alcohol-impregnated caps and following updated central-line care standards. The physicians and nurses looked at de-identified records of 478 patients who received central lines in University of Utah Hospital’s Burn Trauma Intensive Care Unit (BTICU) between April 1, 2011, and March 31, 2015. Study patients were divided into two groups: those who received burn care before Oct. 1, 2013, when the prevention program was started, and those who received burn care after that date. In the 30 months before the program started, 11 patients got central-line infections in the BTICU. But in the 18 months following the program’s inception until the end of the review period, the patient records showed no such infections, the researchers reported.  

Prevention Program Eliminates Bloodstream Infections in Burn Trauma Unit Patients

By implementing a program to prevent bloodstream infections associated with central-line catheters, the University of Utah Health Care Burn Trauma Intensive Care Unit eliminated those hazards entirely, a multidisciplinary committee of the health care system’s nurses and physicians reported in JAMA Surgery.

Prostate Cancer on the Decline

The incidence of prostate cancer among U.S. men declined by nearly 20 percent beginning in 2011, a study of data from 2007 through 2012 shows. Researchers looked at prostate cancer diagnoses by age, race, stage of the disease and Gleason score–the most common system doctors use to grade prostate cancer cells based on the likelihood that a tumor will spread–and found that the decline in the disease occurred among all age groups of men.

Brain Circuits Disrupted in Mice Missing an Autism Gene

Alterations to brain circuits underpinning intellectual disability, autism and other neuropsychiatric disorders appear to be related to subtle cellular changes that occur when a gene is disrupted in the hippocampus–a major part of the brain needed for learning and memory, new research with mice has shown. Variations in the Kirrel3 gene are associated with autism spectrum disorder, intellectual disability and Jacobsen syndrome, a rare developmental disorder.

Megan WilliamsNeurobiology and Anatomy

Physical Therapy May Help Speed Lower Back Pain Recovery, But Problem Often Resolves Over Time

It’s estimated that 70 percent of people will experience low back pain (LBP) at some point in their lives. People with LBP often visit their primary care doctor in search of a prescription to end their pain. Sometimes this involves Physical Therapy (PT). University of Utah researchers found that while PT may hasten recovery somewhat, for many the problem will resolve itself with time.

Julie M. FritzPhysical Therapy

Telemonitoring Aids Diabetes Patients

Diabetes patients whose disease management was overseen by a pharmacist via telemonitoring significantly lowered their A1C levels - a measure of blood sugar - compared to those who received standard diabetes care, a study with 150 patients has shown.

Laura Shane-McWhorterPharmacotherapy

Chlamydia Associated with Fourfold Risk of Gastroschisis

Positive antibody tests for chlamydia trachomatis in pregnant women were associated with almost a fourfold higher risk for gastroschisis in their newborns, a pilot study found. The study included 33 pregnant women whose prenatal ultrasounds showed their fetuses had gastroschisis (cases), a protrusion of the intestine, and sometimes other organs, through a hole in the abdominal wall, and a group of 66 pregnant women (controls) whose ultrasounds showed no fetal abnormalities. Evidence of a recent chlamydia infection in the mothers-to-be was confirmed by blood tests.

Marcia FeldkampPediatrics

Sea Snail's Toxic Venom May Bring Relief for Chronic Pain

University of Utah researchers identified a new potential pain management medication that has implications for the treatment of chronic neuropathic pain due to injury to the nerves, spinal cord or brain. This discovery is the result of a collaborative study of the deadly venom from predatory marine cone snails (Conus generalis) that are indigenous to the South China Sea.

Diabetes Patients Fare Better When Pharmacist Leads Follow-up Care

Type 2 diabetes patients may do better controlling their blood sugar levels when they receive follow-up primary care from a team of providers led by a clinical pharmacist. Further, a study led by a University of Utah College of Pharmacy faculty found that a pharmacist-led Diabetes Collaborative Care Management Program (DCCM) could better control the costs of medical care.

Carrie McAdam-MarxPharmacotherapy

'Cold' Comfort: Freezing Epinephrine is OK

The study provides evidence that epinephrine does not degrade after freezing and thawing, the researchers report. This information is beneficial to those who recreate in the backcountry and have the potential for severe allergic reactions.

Smokers Fare Worse Than Nonsmokers After Spine Surgery

Along with its many other harmful effects, smoking cigarettes appears to adversely affect the outcomes and total costs of patients who undergo surgery for spinal disease.

Meic H. SchmidtNeurosurgery

Smoking Is Not a Primary Risk Factor for Multiple Myeloma

The connection between cigarette smoking and various cancers long has been established, but whether the habit is a risk for multiple myeloma has been an open question. A new study by the International Multiple Myeloma Consortium (IMMC) has found that smoking appears not to be a primary risk factor for the cancer.

Nicola CampBiomedical Informatics

Critical Immune Factors May Haved Adapted to Evade Common Pathogen Inhibitors

Pathogens have evolved multiple means to evade and shut down host immunity. A new study identifies a variety of ways, including amino acid changes on protein surfaces, by which these host factors appear to escape pathogen-mediated inhibition.

Nels C. EldeHuman Genetics

Mutations in RAG1 Gene Linked to Immunodeficiency Diseases

In a multi-institution study published in the Journal Clinical of Immunology, University of Utah researchers and colleagues have extended the spectrum of diseases caused by mutations in the RAG1 gene to include antibody deficiency diseases. Various mutations in the RAG1 gene already were know to cause a number of immune deficiencies, such as severe combined immunodeficiency and Omenn syndrome. RAG1-deficient patients are predicted to have high risk of life-threatening infections, therefore the identification of these mutations suggests treatments not usually considered in patients.

An 'SOS' for Metabolic Stress

Upon viral invasion, the body launches its defenses in an effort to fight the infection. When a protein called PKR binds double-stranded RNA (dsRNA) made by viruses, the act signals that the fight is on. Several years ago, Gökhan Hotamisligil from Harvard University, a collaborator in this study, reported that mice fed an unhealthy, high-fat diet activated PKR even in the absence of viral infection. This result prompted Brenda Bass and her team at the University of Utah to search for molecules that activated PKR during metabolic stress. Unexpectedly, they found that this function was performed by small nucleolar RNAs (snoRNAs) from our own bodies, known primarily for their role in modifying RNA. A key question for future studies is whether the interaction between PKR and snoRNAs can be modulated to control the chronic inflammation that occurs in metabolic stress disorders like obesity and diabetes.

Brenda L. BassBiochemistry

A Critical Link in the Assembly and Spread of HIV-1

To multiply and spread infections, viruses must enter and exit cells. Once inside a cell, many viruses take over the cell’s machinery to produce new viral particles and release them into the surroundings. Some viruses—including HIV-1—exit the cell in a manner that wraps them in membrane from the host cell. A virus protein called Gag is required for the release of HIV-1 and other retroviruses. In some cases, Gag proteins bind directly to members of the NEDD4 protein family to facilitate virus release. However, the Gag protein from HIV-1 does not appear to interact directly with NEDD4 proteins, so it was not clear how this virus connects to these proteins. In a study with laboratory-grown human cells, University of Utah researchers show that members of another human protein family called the Angiomotins are required to wrap the HIV-1 virus in membrane, act as a link between Gag and NEDD4L (one member of the NEDD4 family), and are necessary for efficient virus release from human cells.

Genetic Counseling Helps Parents Cope with 'Uncertain' Genetic Test Result in Children

Chromosomal microarray is the recommended first-tier genetic test when a child presents with idiopathic developmental delay, intellectual disability, and/or autism spectrum disorder. This type of testing, which can simultaneously detect genetic abnormalities on all chromosomes, may discover variants of unknown clinical significance (VUS). When a genetic test determines a child’s disability or disorder is “uncertain,” it can cause parental stress and anxiety. In this study, University of Utah researchers surveyed parents of children with a disability or disorder about their understanding of an uncertain genetic test result and its impact on stress and anxiety. Parents reported that this result was important for understanding their child’s diagnosis and they were satisfied with the information. A majority of parents reported high confidence in their ability to explain an uncertain genetic test result to others. Many of them also stated they received support from a genetic counselor. Based on these survey results, uncertain genetic results are important to parents of children with VUS and genetic counseling regarding uncertain results contributes positively to both parental understanding and support. Stephanie Jez, a student in the University of Utah Graduate Program in Genetic Counseling, led the project.

Alveolar Soft Part Sarcoma Thrives on Lactate

Model systems for the study of cancer come in many varieties. Each model transfers some aspect of a human cancer into an experimental setting, such as a culture dish or animal model, to recreate features of the cancer and teach researchers more about its cell biology.  The point of any model's experimental setting is to enable direct testing of cause and effect relationships. Researchers led by Kevin B. Jones, M.D., transferred no more than a single gene from a human cancer called alveolar soft part sarcoma into a mouse. That gene alone then generated a very precise mimic of the original cancer, proving that the gene serves as the central driver of alveolar soft part sarcoma. Further testing with the mice that spontaneously grew these sarcomas further demonstrated that this particular cancer type prefers to grow in tissues with high levels of lactate, a byproduct made when sugar breaks down. By altering the concentrations of lactate to which a tumor was exposed, the investigators were able to alter its growth and behavior. Contrary to old dogma that considered lactate only a waste product, the team proved that these cancers soak in lactate from their surroundings and thrive on it. Work is under way to test means of blocking this use of lactate as a means of stopping tumor growth.

JodyRosenblatt2-19

A single layer of cells acts like a protective skin for the organs in the human body, but this protective layer also is prone to forming tumors. Normally, these protective cells are dividing constantly and when they become too numerous, some are kicked out to die by a process these researchers have found called “extrusion.” Recently, they found that extrusion is defunct in some of the most aggressive tumors—pancreatic and lung carcinomas—and that instead of dying the cells accumulate and are resistant to chemotherapy. Additionally, some cells can pop into instead of out of the tissue, which could enable them to move to other organs and metastasize—an even more deadly prospect. From learning this basic cellular mechanism for how cells should die, the researchers identified a chemical way to bypass the defects seen in pancreatic cancer without affecting the normal tissue, which could provide a new therapy for these deadly tumors.

Clark2-19

Although undocumented residents comprise an estimated 28 percent of the foreign-born U.S. population, their care is less costly and their use of emergency services less frequent than their native-born counterparts. That’s not necessarily good news. Undocumented residents may avoid seeking health care because they are twice as likely to be uninsured or because they fear surveillance or deportation when accessing health services. Their absence from the health care arena partially explains undocumented residents’ health care disparities. “Nurses have an ethical responsibility to advocate for undocumented individuals’ access to care,” wrote Lauren Clark, Ph.D., FAAN, University of Utah professor of nursing and co-author of a piece examining the issue of health care for undocumented residents. “Advocacy might include assuring a qualified interpreter is present for care. Sometimes advocacy is listening to a person’s life experience and humanizing their care during that encounter.” Clark conducted the study with colleagues at the University of South Carolina and University of Arizona.

DavidSkarda2-19

As the cost of U.S. health care continues to skyrocket, University of Utah surgeons and other researchers have found a way to both decrease cost and improve outcomes as they treat appendicitis, the most common surgical emergency in children. In a study with 580 patients treated for non-ruptured appendicitis, they found that introducing a protocol to eliminate variability in treatment could reduce the duration of hospital stay and total cost of care by 20 percent, while decreasing the rate of readmission, reoperation and other complications. The protocol standardized everything from the evaluation to diagnose appendicitis to the type, dose, duration and timing of prescribing antibiotics before surgery. David E. Skarda, M.D., the study’s first author, says this shows how applying principles learned in the manufacturing industry to health care is safe, decreases cost and improves outcomes. 

A “Hybrid” Approach to Urine Testing for Compliance with Long-Term Drug Use

Urine drug testing is a common tool for evaluating compliance with long-term, prescribed medications, such as for managing chronic pain, and for assuring abstinence from illegal or non-prescribed medications. This "compliance testing" requires a different approach from the traditional urine drug testing that is common to the workplace, military or among athletes. The approach for compliance testing is not currently standardized. To address this, University of Utah and Associated Regional University Pathologists (ARUP) researchers developed a unique method for urine drug testing that is designed specifically to meet the needs of compliance testing.  The approach is called a "hybrid" because it combines several analytical methods, including high-resolution mass spectrometry and immunoassays, that were selected to optimize quality of testing and time to result, as well as to reduce the overall costs of testing.

Chemical Warfare: Cone Snails Use Insulin as Weapon to Disable Fish

Cone snails lack the speed and other advantages that most predators use, but they’ve made up for it by evolving a venom cocktail that disables fish and, a new study reveals, includes a weaponized form of insulin. A synthetic form of the insulin caused blood glucose levels to plummet when injected into zebrafish and also disrupted swimming behavior in fish exposed to it through water contact. The researchers propose that adding the insulin to the cone snail’s venom cocktail enables some types of the predatory snails to disable entire schools of fish with hypoglycemic shock. The snail insulin potentially can aid researchers in studying how the human body controls blood sugar and energy metabolism.

Multiple C-sections Linked to Ectopic Pregnancies

Women who delivered two or three babies through cesarean section were at a substantially higher risk for a subsequent ectopic pregnancy compared with women who gave vaginal birth or had one C-section, University of Utah researchers report in a recent study. Using the Utah Population Database, a unique storehouse of genealogical, health and public records, the researchers evaluated 255,082 women who gave live birth in Utah between 1996 and 2011. They found that those with two of two, two of three, or three of three prior C-sections were 1½ to 3½ times more likely to have ectopic pregnancies than women who’d never had a C-section. Women who had one prior cesarean section delivery faced no greater risk than women who’d given vaginal birth.  These findings underscore another downstream risk of the increasing rate of cesarean delivery.

Retinal Swelling Sensor Identified as Possible Target for Treating Eye and Brain Diseases

Researchers identified the cellular mechanism that controls swelling in retinal cells, a discovery with implications for treating brain and eye diseases and traumas resulting from swelling. Their study brings three new insights: First, it identifies an ion channel (TRPV4) as the retina’s swelling sensor and shows it is activated and regulated differently in neurons versus glial cells (the most numerous cells in the central nervous system.)  Second, it determines the molecular link between glial swelling and inflammatory signaling by linking TRPV4 activation to a fatty acid known to exacerbate brain pathology during swelling. Third, it shows that calcium signaling in retinal neurons and glial cells is required in the cells’ response to swelling and mechanical stress. These discoveries mean the TRPV4 ion channel might be targeted to treat brain and eye diseases related to swelling.      

Scalpel or Scope? Costs Influence Consumers

Consumer price comparison is almost nonexistent in the U.S. health care system, but University surgeons show in a study that when given the choice between a less costly "open" operation or a pricier laparoscopy for their children's appendicitis, parents were almost twice as likely to choose the less expensive procedure - when they were aware of the cost difference.

The study, shows that providing pricing information upfront can influence patient choice of surgical procedures and potentially lead to cost savings in health care, a sector of the economy that accounts for more than 17 percent of the U.S. Gross Domestic Product, says Eric R. Scaife, M.D., senior author, associate professor of surgery and chief of pediatric surgery. Surgery resident Katie W. Russell, M.D., is the study's first author.

Mouse Model Provides Window into the Working Brain

University of Utah scientists developed a genetically engineered line of mice that is expected to open the door to new research on epilepsy, Alzheimer's and other diseases.

The mice carry a protein marker, which changes in degree of fluorescence in response to different calcium levels. This will allow researchers to study many cell types, including astrocytes and microglia, in a new way. John White, Ph.D., professor of bioengineering and executive director of the Brain Institute, is corresponding author of the study. Peter Trvdik, Ph.D., a fellow in human genetics, is senior author, and J. Michael Gee, who is pursing and M.D. and graduate degree in bioengineering, is first author.

8,000-Year-Old Mutation Key to Human Life at High Altitude

Researchers long have known of a connection between mitochondrial function and distribution and neural disease, but they hadn’t been able to tell whether a defect occurs because mitochondria isn’t functioning properly or isn’t getting to the right.

Biochemistry professor Janet Shaw, Ph.D., and M.D./Ph.D. student Tammy T. Nguyen led a study that addressed that question and found that when mitochondria weren’t distributed along the spinal cord and axons in mouse models they developed, the animals developed symptoms of neurodegenerative diseases.

If Mitochondria Don't Move, Motor Neuron Disease May Develop

Researchers long have known of a connection between mitochondrial function and distribution and neural disease, but they hadn’t been able to tell whether a defect occurs because mitochondria isn’t functioning properly or isn’t getting to the right.

Biochemistry professor Janet Shaw, Ph.D., and M.D./Ph.D. student Tammy T. Nguyen led a study that addressed that question and found that when mitochondria weren’t distributed along the spinal cord and axons in mouse models they developed, the animals developed symptoms of neurodegenerative diseases.

Janet Shaw