Academics & Research

Research

2015

From genetics to geriatrics, physical therapy to pharmacology: University of Utah Health is making discoveries that are pushing the frontiers of science and medicine. The Driving Discovery blog and News Room feature the latest research highlights.

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.

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. 

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.

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.

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.