Discoveries – Discovery and Innovation at University of Utah Health

August 1, 2025June 19, 2026

How a Key Protein May Protect the Liver from Cancer Caused by Fatty Liver Disease

Liver cancer is one of the leading causes of cancer deaths worldwide. In the United States, rising rates of liver cancer have been tied to an increased prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), a condition in which excess fat accumulates in the liver. As obesity, diabetes, and other metabolic disorders become increasingly common, MASLD does too, putting more and more people at risk of progressing to serious liver disease, and to liver cancer.

Scientists led by Mei Koh, PhD, associate professor of Pharmacology and Toxicology, have identified a protein that appears to protect the liver from the changes that link fat accumulation to cancer development. This protein, called HAF, is present in healthy livers. But when Koh and her team examined livers with excess fat from humans or mice, they found that HAF was depleted. In experiments with mice, they showed that low levels of HAF put animals at higher risk for fatty livers which ultimately progressed to liver cancer. They learned that HAF acts on a growth-regulating pathway that drives cancer progression. In livers where HAF levels are low, deregulation of this pathway spurs cell death and inflammation, which can cause tumor develoment.

For Koh, who founded the biotechnology company Kuda Therapeutics to translate her lab’s findings into cancer therapies, is focused on finding ways to improve patients’ lives. Her team has identified key pro-oncogenic proteins that are suppressed by the liver-protecting HAF. When HAF is lost, levels of these proteins increase leading to liver disease, suggesting that these proteins could serve as therapeutic targets. The work suggests that manipulating these proteins might be a way to protect vulnerable livers from cancer development or to treat liver cancer after it is diagnosed.

References:

HAF prevents hepatocyte apoptosis and progression to MASH and HCC through transcriptional regulation of the NF-κB pathway. Acuña-Pilarte K, Reichert EC, Green YS, Halberg LM, Golkowski M, Maguire KM, Mimche PN, Kamdem SD, Hu PA, Wright J, Ducker GS, Voth WP, O’Connell RM, McFarland SA, Egal ESA, Chaix A, Summers SA, Reelitz JW, Maschek JA, Cox JE, Evason KJ, Koh MY. Hepatology. 2025 Aug 1;82(2):438-453.

Press Releases and Media:

University of Utah Health: Scientists Find Soft Sea Corals are Source of Sought-After “Anti-Cancer” Compound

Governor’s Office of Economic Opportunity
The Utah Daily Chronicle

How a Key Protein May Protect the Liver from Cancer Caused by Fatty Liver Disease | PI: Mei Koh, PhD

March 18, 2025June 19, 2026

Boosting Memory During Sleep

While our bodies rest, our brains keep learning, replaying experiences to solidify our memories and improve our future performance. Genevieve Albouy, PhD, an associate professor in the Department of Health & Kinesiology at the University of Utah College of Health, studies this process of memory consolidation, looking for ways learning might be enhanced. Her group’s work could help researchers find ways to improve motor learning when it declines due to aging or neurological disease.

Patterns of neural activity associated with new skills can be replayed by the brain spontaneously, which is important for long-term memory storage. Those patterns can also be provoked with cues linked to the learning experience, in a procedure known as targeted memory reactivation. Albouy and her team used this approach to reactivate the memory of the sequence of movements people learned during the day. Participants heard a sound before they began learning the sequence, then again while they slept after their lesson. When the memory was reactivated with sound while they slept, they were able to complete the sequence more quickly after their nap. After a full night’s sleep, they were able to do it even faster, and the performance-enhancing effect of memory reactivation persisted. The team found that the memory-reactivating sound cues work best in specific time windows during the brain’s slow waves that are critical for neuroplasticity during sleep. Their work exploring how targeted memory reactivation impacts both behavior and brain activity could help researchers find ways to improve motor learning when it declines due to aging or neurological disease.

References:

Sigma oscillations protect or reinstate motor memory depending on their temporal coordination with slow waves. Nicolas J, King BR, Levesque D, et al. Elife. 2022;11:e73930.

Unraveling the neurophysiological correlates of phase-specific enhancement of motor memory consolidation via slow-wave closed-loop targeted memory reactivation. Nicolas J, King BR, Lévesque D, et al. Nat Commun. 2025;16(1):2644.

Press Releases and Media:

University of Utah Health: ZZZs Please: New Research Shows How to Boost Memory During Sleep

Boosting Memory During Sleep | PI: Genevieve Albouy, PhD

March 7, 2025June 19, 2026

Microbial Support for Insulin Production

Type 1 diabetes affects more than 2 million people in the United States, many of whom have been managing their disease since childhood. Its symptoms appear after the immune system destroys insulin-producing cells in the pancreas, preventing the body from controlling the amount of sugar in the blood. Healthy pancreases release insulin to modulate cells’ access to sugar as needs change moment to moment. But people with diabetes must rely instead on insulin delivered via a pump or injections to keep their blood sugar levels safe. Researchers have been exploring how the pancreas’s insulin-producing cells are formed, in the hopes that they might one day be able to restore them after they have been lost.

Charles Murtaugh, PhD, June Round, PhD, and Zac Stephens, PhD, discovered that development of these cells—known as beta cells—depends on the early-life presence of certain microbes that live in the gut. When the researchers treated infant mice with antimicrobial medications, altering their microbiomes during a key window for pancreas development, mice grew up with fewer beta cells and elevated levels of sugar in their blood. They were able to identify specific bacteria and fungi that promoted beta cell growth during development. This increased the insulin-producing capacity of the pancreas and protected mice from diabetes later in life. Remarkably, they could even use these microbes to restore insulin production in adult mice. Their findings could lead to new diabetes treatments or prevention strategies.

References:

Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development. Hill JH, Bell R, Barrios L, et al. Science. 2025;387(6738)

Press Releases and Media:

University of Utah Health: Early-Life Gut Microbes May Protect Against Diabetes, Research in Mice Suggests

Microbial Support for Insulin Production | PI: June L. Round, PhD, Zac Stephens, PhD & Charles Murtaugh, PhD

February 20, 2025June 19, 2026

Metabolite Biosensors for Live Imaging

The molecules inside our bodies are in constant flux as our cells break down food, produce and store energy, and generate the materials they need to keep us healthy. Amidst this metabolic activity, one particularly influential molecule is acetyl-CoA. Cells depend on acetyl-CoA to produce structural materials, signaling molecules, and energy. It may also help cells monitor and adjust their own metabolism by regulating gene activity, which is vital for ensuring essential molecules are available when needed.

Scientists can now get a clear picture of acetyl-CoA inside human cells, thanks to a new sensor developed by Department of Medicinal Chemistry assistant professor Katherine Diehl, PhD and her team. The sensor lights up living cells with a green color that intensifies as acetyl-CoA levels rise, giving scientists a way to track the molecule in real time.

With the Diehl lab’s sensor, researchers are better equipped to investigate acetyl-CoA’s roles inside human cells, including how its disruption contributes to diseases like cancer and neurodegeneration. The sensor also works in bacterial cells, meaning scientists can use it to monitor bacteria whose metabolic pathways have been engineered to generate useful products, such as biofuels.

References:

A genetically encoded fluorescent biosensor for visualization of acetyl-CoA in live cells. Smith JJ, Valentino TR, Ablicki AH, Banerjee R, Colligan AR, Eckert DM, Desjardins GA, Diehl KL. Cell Chem Biol. 2025 Feb 20;32(2):325-337.e10.

Metabolite Biosensors for Live Imaging | PI: Katherine Diehl, PhD

January 29, 2025June 19, 2026

Adopting Nature’s Chemistry

High atop mountains and deep in the sea, animals make molecules that help them thrive in their ecological niches. Many of them make good medicines. But when it comes to getting medicines based on natural products to patients, it’s not usually practical to retrieve enough of a natural compound from the organism in which it was first found to enable drug development and testing. Scientists must find a way to scale up production.

To protect themselves against predators, soft corals make a diverse array of chemicals called terpenes. Many of these defensive compounds show promise as potential therapies for cancer or chronic pain. Paul Scesa, PhD, who worked in the lab of medicinal chemist Eric Schmidt, PhD, studied a soft coral that makes an anti-inflammatory terpene, pseudopterosin. By analyzing the animal’s genome, as well as the genomes of related corals, Schmidt’s team was able to identify enzymes that are used for pseudopterosin production in nature. By programing microbes to make the same enzymes, scientists can now bring the production of these compounds into the lab, rather than harvesting them from the ocean’s corals.

Schmidt’s team also studies chemicals called polyketides, many of which treat cancers or infections. Most polyketides were found in microbes, but new work reveals a previously hidden world of potential drugs in animals. Working with biochemist Chris Hill, DPhil, vice dean of research for the School of Medicine, research professor Heidi Schubert, PhD, and postdoctoral scientist Feng Li, PhD, captured detailed images of two polyketide-making enzymes from sea slugs. Like a robotic assembly line, the enzymes use an arm to move pieces into place. By understanding those motions, the team defined a key step in molecule building in animals, aiding the discovery and creation of new biotech tools and pharmaceutical leads.

References:

Pseudopterosin Biosynthesis: Unravelling a Decades Old Problem in Animal Specialized Metabolism. Scesa PD, Schmidt EW. J Am Chem Soc. 2025 Jan 29;147(4):3072-3079.

The structure of full-length AFPK supports the ACP linker in a role that regulates iterative polyketide and fatty acid assembly. Schubert HL, Li F, Hill CP, Schmidt EW. Proc Natl Acad Sci U S A. 2025 Feb 11;122(6):e2419884122.

Press Releases and Media:

University of Utah Health: Scientists Find Soft Sea Corals are Source of Sought-After “Anti-Cancer” Compound

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Adopting Nature’s Chemistry | PI: Eric W. Schmidt, PhD & Christopher P. Hill, DPhil

January 9, 2025June 19, 2026

Shared Decision Making Strategies for Stroke Prevention

Millions of people in the United States live with atrial fibrillation (AFib), an abnormal heart rhythm that causes blood to pool in the heart, where it can form clots that can cause stroke. This risk can be significantly reduced by taking anticoagulant medications. There are several options to reduce the likelihood of blood clots but each has drawbacks. Medications that slow clotting inevitably cause patients to bleed more easily, and some require frequent blood tests to ensure dosing is safe and effective. Some newer drugs require less monitoring, but are more costly for patients. What works for one person may not be the best choice for another.

Two tools developed by Elissa Ozanne, PhD, an associate professor in the Department of Population Health Sciences, help doctors and their patients make treatment decisions together. To help people prepare for conversations with their doctor, Ozanne developed interactive educational materials that can be used at home or in a doctor’s waiting room. A second tool facilitates patient-provider conversations during clinic visits. In a clinical study, these tools improved patient knowledge and shared decision-making, which is expected lead to better health outcomes.

References:

Effectiveness of shared decision making strategies for stroke prevention among patients with atrial fibrillation: cluster randomized controlled trial. Ozanne EM, Barnes GD, Brito JP, et al. BMJ. 2025;388:e079976.

Shared Decision Making Strategies for Stroke Prevention | PI: Elissa Ozanne, PhD

December 12, 2024June 19, 2026

Evolution-Resistant Antibodies

Before vaccines were available in the first years of the COVID-19 pandemic, researchers had engineered antibodies that could block SARS-CoV-2, the virus that causes the disease, to prevent infection or reduce the severity of illness. But as the virus evolved, these drugs stopped working. Antibodies work by binding specific sites on the virus. Antibiotic resistance arises when mutation causes those sites to change.

Biochemist Tyler Starr, PhD, has been searching for an antibody that the virus can’t escape. Starr and collaborators at Vir Biotechnology and the University of Washington have developed an antibody that tolerates variability in its target region, allowing it to tightly bind SARS-CoV-2 and dozens of related viruses. The group is the first to show that a monoclonal antibody can be both potent and active against a broad range of SARS-related coronaviruses. That antibody neutralized every SARS-CoV-2 variant the team tested. It was equally effective at stopping dozens of related coronaviruses that infect bats, but not humans. The results indicate that the antibody could be useful if, in the future, another SARS-related virus evolves the ability to infect humans.

References:

A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification. Rosen LE, Tortorici MA, De Marco A, et al. Cell. 2024;187(25):7196-7213.e26.

Evolution-Resistant Antibodies | PI: Tyler Starr, PhD

June 14, 2024June 19, 2026

The Brain’s Medial Entorhinal Cortex Keeps Track of Time

Clocks are essential for keeping us in sync with the rhythms of the world, but we also rely our brain’s own awareness of the passage of time. Many different parts of the brain are involved in timekeeping, capturing information about time in patterns of neural activity, then using that information to make sense of events and coordinate actions. When injury or disease damages that circuitry, it can skew the way we remember the past and make it harder to plan for the future. It can even interfere with the ways we move and communicate.

Neuroscientist Jim Heys, PhD, has watched this neuronal timekeeping in action. To encourage mice to keep track of time, his team challenged mice to complete a complex task. They were exposed to a strong odor for a few seconds at a time, then given the opportunity to earn a reward by comparing the duration of pairs of scents. Heys and his colleagues found cells in a part of the brain called the entorhinal cortex that were essential for this task. The time cells they found changed their behavior as mice became more adept at discriminating the relative timing of odors, suggesting they may be important for understanding temporal relationships. The Heys Lab is now investigating how the brain balances time with reward to evaluate the value of an action. One benefit of understanding how the entorhinal cortex processes time could be earlier diagnosis of Alzheimer’s disease, which typically begins in this part of the brain.

References:

Medial entorhinal cortex mediates learning of context-dependent interval timing behavior. Bigus ER, Lee HW, Bowler JC, Shi J, Heys JG. Nat Neurosci. 2024;27(8):1587-1598.

Press Releases and Media:

University of Utah Health: “Time Cells” In the Brain Are Critical for Complex Learning, Study Shows

The Brain’s Medial Entorhinal Cortex Keeps Track of Time | PI: Jim Heys, PhD

April 29, 2024May 30, 2025

Identification of GGC Expansion as a Basis for SCA4 Movement Disorder

Spinocerebellar ataxia type 4 (SCA4) is a rare movement disorder whose symptoms begin in adolescence or adulthood, usually with difficulty walking and balancing. Affected individuals may go on to experience muscle weakness, lose sensation in their hands and feet, and lose their reflexes. The condition is inherited, but until recently, its specific genetic cause was unknown, because the mutation associated with SCA4 falls within a region of DNA that is particularly difficult to analyze. With the latest DNA sequencing technology, U of U Health scientists led by neurologist Stefan Pulst, MD, were finally able to pinpoint the genetic cause of SCA4: a stretch of repetitive DNA in a gene called ZFHX3 that is longer than it should be.

Knowing the genetic cause of SCA4 provides relief for patients and their families, who can now be tested for the mutation. The discovery has also enabled Pulst and his team to dig into why expansion of the ZFHX3 gene harms neurons, which they hope will open a path toward an effective treatment. The team’s experiments suggest the abnormal ZFHX3 protein encoded by the mutated gene interferes with neurons’ ability to recycle unwanted proteins and other cellular debris. A drug designed to overcome defects in this type of cellular recycling is already being tested in clinical trials for another movement disorder, SCA2. Given the similarities they have uncovered, the researchers say it’s possible that treatment might benefit patients with SCA4, too.

References:

A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy. Figueroa KP, Gross C, Buena-Atienza E, et al. Nat Genet. 2024;56(6).

Press Releases and Media:

University of Utah Health: After 25 Years, Researchers Uncover Genetic Cause of Rare Neurological Disease

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Identification of GGC Expansion as a Basis for SCA4 Movement Disorder | PI: Stefan M. Pulst, MD

February 15, 2024March 27, 2025

PNMA2 Forms Immunogenic Non-Enveloped Virus-Like Capsids Associated with Paraneoplastic Neurological Syndrome

Graphic - Jason Shepherd, PhD. PI, PNMA2 Forms Immunogenic Non-Enveloped Virus-Like Capsids Associated with Paraneoplastic Neurological Syndrome

For people with a rare cancer-associated condition called paraneoplastic syndrome, sudden memory loss, loss of coordination, or other neurological symptoms are often the first sign that a tumor is growing somewhere in the body. The symptoms are caused by the immune system’s response to it. It turns out that some tumors produce brain proteins. As the immune system learns to recognize and destroy tumor cells, it can also begin to target healthy neurons. This is because neurons naturally produce molecules that aren’t found on healthy cells elsewhere in the body. It has remained a mystery why only specific brain proteins made by neurons cause paraneoplastic syndromes.

In the lab of U of U Health neurobiologist Jason Shepherd, PhD, researchers are studying a protein called PNMA2 that is normally expressed in the brain but associated with paraneoplastic syndromes. They have found that PNMA2 molecules are released from both tumors and brain cells. In both cases, the proteins assemble into a larger structure that resembles similar structures formed by viruses. Graduate student Junjie Xue found that injecting PNMA2 proteins into mice provoked a particularly strong immune reaction—but only when the proteins assembled into the virus-like structure. Strikingly, the mice developed deficits in learning and memory that resembled the neurological symptoms experienced by paraneoplastic patients. By figuring out exactly how and why paraneoplastic syndrome causes the immune system to attack the brain, Shepherd and his team hope to uncover potential treatment strategies.

References:

PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. Xu J, Erlendsson S, Singh M, et al. Cell. 2024;187(4):831-845.e19. doi:10.1016/j.cell.2024.01.009.

Press Releases and Media:

University of Utah Health: Brain Protein’s Virus-Like Structure May Help Explain Cancer-Induced Memory Loss

Live Science
Neuroscience News

PNMA2 Forms Immunogenic Non-Enveloped Virus-Like Capsids Associated with Paraneoplastic Neurological Syndrome | PI: Jason Shepherd, PhD

December 28, 2023June 19, 2026

Local Drug Delivery Device to Control Stubborn Infections

When bacteria settle into a wound or surgical site as a microbial community known as a biofilm, the infection can be notoriously difficult to treat. Microbes in a biofilm hibernate inside a protective matrix, largely out of reach of systemic antibiotics, allowing the infection to stubbornly persist. Treating biofilm infections requires strong local antibiotics, delivered over a prolonged period—and that has been difficult to achieve. A new drug delivery device developed by Dustin Williams, PhD, a professor of orthopaedics and Nicholas Ashton, PhD, a research assistant professor of orthopaedics, does exactly that. Their Purgo Pouch is refillable and allows antibiotics to diffuse through a rate-controlling membrane directly into the site of infection. It can be used without complex medical equipment, making it practical for use in conflict zones or disaster relief.

In recognition of its potential to address an important medical problem, the FDA designated the Purgo Pouch as a Breakthrough Device, which accelerated several aspects of review and development. First-in-human clinical trials are anticipated to begin in mid-2027. Meanwhile, the new technology is already changing infection management for veterinary patients. Horses, cats, and dogs have all benefitted from the Vetlen Pouch developed by Williams and Ashton, which uses the same rate-controlling membrane to deliver continuous medication to infection sites for up to 30 days.

References:

Purgo Scientific
Vetlen

Press Releases and Media:

University of Utah Health: University of Utah Orthopaedics Researchers Lead Innovative Purgo Pouch Development, Pioneering Solutions for Open Fracture Infections; How Biomedical Innovation is Healing Animals to Help People

Local Drug Delivery Device to Control Stubborn Infections | PI: Dustin Williams, PhD & Nicholas Ashton, PhD

December 12, 2023May 9, 2025

Risks of Cannabis During Pregnancy

Cannabis use is increasing among reproductive age females. However, the effects of cannabis use on pregnancy and pregnancy outcomes remains largely unknown. Torri Metz, MD, MS, vice chair of research of obstetrics and gynecology, and Robert Silver, MD, professor and chair of obstetrics and gynecology, examined if cannabis use during pregnancy was associated with adverse pregnancy outcomes mediated by the placenta.

They analyzed the pregnancy outcomes of more than 9,000 people, including 610 who used cannabis during their pregnancies. Because self-reports of cannabis use can be unreliable, they used urine samples to estimate study participants’ exposure. After controlling for variables like socioeconomic status, nicotine use, and certain medical conditions

they found that individuals who used cannabis had a higher frequency of a composite adverse outcome which included small for gestational age babies (<5^th percentile for age and sex), hypertensive disorders of pregnancy, medically indicated preterm birth and stillbirth. In addition, they found that ongoing use throughout pregnancy, and heavier use were associated with a higher risk of adverse pregnancy outcomes. Information about the risks of maternal cannabis use will be critical in counseling patients so they can make informed decisions about cannabis use during pregnancy.

References:

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function. Metz TD, Allshouse AA, McMillin GA, et al. JAMA. 2023;330(22):2191–2199. doi:10.1001/jama.2023.21146

Press Releases and Media:

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Risks of Cannabis During Pregnancy | PI: Robert M. Silver, MD & Torri D. Metz, MD, MS

December 4, 2023June 19, 2026

Talazoparib Plus Enzalutamide Increases Survival Rates in Men with Metastatic Castration-resistant Prostate Cancer

Photo of researchers for "Talazoparib plus enzalutamide increases survival rates in men with metastatic castration-resistant prostate cancer"

Prostate cancer is the second most common cause of cancer deaths for men in the United States. Worldwide, more than a million new cases are diagnosed each year. Treatment often includes drugs that rein in the cancer by blocking hormones that spur its growth. But as the disease progresses, many tumors become less sensitive to this type of treatment. Based on laboratory studies, Neeraj Agarwal, MD, an oncologist and physician-scientist at Huntsman Cancer Institute and professor of internal medicine, suspected that an enzyme called PARP might help prostate cancer cells resist hormone therapy. He co-led a global clinical trial exploring whether adding a drug that inhibits PARP to the standard therapy enzalutamide could improve outcomes for patients.

More than 1,000 patients participated in the trial at hundreds of hospitals and clinics worldwide. Agarwal and his colleagues found that the new drug combination stopped the growth of hormone-resistant prostate cancers (also known as castration-resistant prostate cancers) for a longer period than enzalutamide alone. Based on their findings, the US Food and Drug Administration (FDA) approved the combination therapy as a treatment for metastatic castration-resistant prostate cancers with certain genetic mutations in 2023. More recently, the team has found that the treatment extends survival for patients with metastatic hormone-resistant prostate cancer, regardless of whether those mutations are present or the type of mutations.

References:

Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Agarwal N, Azad AA, Carles J, et al. Lancet. 2023;402(10398):291-303.

First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial. Fizazi K, Azad AA, Matsubara N, et al. Nat Med. 2024;30(1):257-264.

Press Releases and Media:

Huntsman Cancer Institute: Novel Prostate Cancer Treatment Increases Overall Survivor Rates For Late-Stage Prostate Cancer Patients

Talazoparib Plus Enzalutamide Increases Survival Rates in Men with Metastatic Castration-resistant Prostate Cancer | PI: Nareej Agarwal, MD

November 22, 2023March 27, 2025

Diabetes Drug Protects Against Muscle Loss

As we get older, it can be harder to bounce back from injury or prolonged periods of bed rest. That’s partly because it takes older adults longer to rebuild muscles that have atrophied due to disuse. The resulting weakness can limit mobility and put people at risk for falls, hospitalization, and even chronic disease. Encouragingly, it may be possible to protect older adults against muscle loss with a drug that millions of people already take.

That drug, metformin, helps to control blood sugar and is commonly used to treat diabetes. But it also changes the behavior of cells that can influence muscle regeneration and growth. When professor of physical therapy and athletic training Micah Drummond, PhD, and colleagues gave metformin to people over the age of 60 before and during a five-day period of bed rest, those individuals experienced less muscle atrophy than people who spent the same five days in bed, but took only a placebo. Participants’ muscles also had less fibrosis—a hardening of the tissue that can interfere with function—if they took metformin. Drummond and his colleagues think that’s because metformin limits senescence, a state in which cells tend to secrete factors that promote inflammation. He and his team are excited about the prospect of deploying metformin, a drug that is considered inexpensive and safe, to get people back on their feet faster.

References:

Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment. Petrocelli JJ, McKenzie AI, de Hart NMMP, Reidy PT, Mahmassani ZS, Keeble AR, Kaput KL, Wahl MP, Rondina MT, Marcus RL, Welt CK, Holland WL, Funai K, Fry CS, Drummond MJ. Aging Cell. 2023 Nov;22(11):e13936.

Press Releases and Media:

University of Utah Health: “A Common Diabetes Drug Has a Surprising Side Gig: Muscle Protector”

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Diabetes Drug Protects Against Muscle Loss | PI: Micah J. Drummond, PhD

September 22, 2023March 27, 2025

Regulation and Remodeling of Membrane Microdomains of Cardiomyocytes During Heart Failure Progression

Millions of people worldwide live with heart failure, meaning their hearts can’t pump blood through the body as well as they should. That can lead to fatigue and shortness of breath, as the body struggles to get the oxygen it needs. Heart failure is a chronic, progressive condition, and as the heart weakens, everyday activities can become difficult. Some patients eventually require a heart transplant or a surgically implanted device like a defibrillator or a left ventricular assist device to survive. At U of U Health, scientists are learning how the molecular organization of heart cells changes as heart failure progresses, and using that knowledge to pioneer potential gene therapy for heart disease.

Associate Professor of Pharmacology and Toxicology TingTing Hong, PhD, and Robin Shaw, MD, PhD, director of the Nora Eccles Harrison Cardiovascular Research and Training Institute have zeroed in on a protein that helps organize molecules and channels on the outer surface of the heart’s muscle cells that are critical for coordinating the heart’s rhythmic contractions. Levels of that protein, cBIN1, tend to decline with heart failure, worsening the condition. Hong, Shaw and colleagues have found that gene therapy that restores cBIN1 can improve heart function in laboratory animals with heart failure. They’ve had success using cBIN1 gene therapy to restore function in animals whose hearts have been damaged by a lack of blood flow, similar to the myocardial ischemia patients can experience when an artery is blocked, as well as in non-ischemic cardiac myopathy. Their findings in animal models have paved the way to developing an innovative gene therapy for patients.

References:

Cardiac gene therapy treats diabetic cardiomyopathy and lowers blood glucose. Li J, Richmond B, Cluntun AA, Bia R, Walsh MA, Shaw K, Symons JD, Franklin S, Rutter J, Funai K, Shaw RM, Hong T. JCI Insight. 2023 Sep 22;8(18).

Press Releases and Media:

University of Utah Health: “New Gene Therapy Reverses Heart Failure in Large Animal Model”

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Regulation and Remodeling of Membrane Microdomains of Cardiomyocytes During Heart Failure Progression | PI: TingTing Hong, MD, PhD & Robin M. Shaw, MD, PhD

March 22, 2023May 9, 2025

Uncovering Disparities that Impact Heart Health

About 40 million adults in the United States take statin drugs to reduce their risk of heart disease and stroke. The drugs, which lower levels of LDL cholesterol, are considered safe for most people, and for many, their potential benefits are high. Many people who might benefit from statins, however, aren’t taking them.

Graduate student Joshua Jacobs and Adam Bress, PharmD, MS, associate professor of population health sciences, analyzed data from National Health and Nutrition Examination Surveys completed between 2013 and 2020 and found the drugs are underutilized, particularly among Black and Hispanic Americans. Jacobs looked at data from more than 3,400 people and found that only about 30 percent of those with the highest risk of developing a cardiovascular problem in the next 10 years were taking statins. While 28 percent of White participants were being treated with the drugs, only 15 percent of Hispanic and 20 percent of Black participants were.

Although statins are among the most prescribed drugs in the United States, many patients who might benefit aren’t taking them. The findings highlight disparities in care and a need to identify barriers to treatment.

Graphic - Uncovering Disparities that Impact Heart Health

References:

Prevalence of Statin Use for Primary Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and 10-Year Disease Risk in the US: National Health and Nutrition Examination Surveys, 2013 to March 2020. Jacobs JA, Addo DK, Zheutlin AR, et al. JAMA Cardiol. 2023;8(5):443–452. doi:10.1001/jamacardio.2023.0228

Press Releases and Media:

University of Utah Health: Certain Racial, Ethnic Groups Less Likely to Receive Preventive Heart Disease Treatment

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Uncovering Disparities that Impact Heart Health | PI: Adam Bress, PharmD

March 10, 2023May 30, 2025

Finding Inspiration for Drug Development in Metabolic Regulators

The metabolic pathways that shape how our bodies use nutrients and energy are under constant adjustment, with metabolites pay a key role in managing their function and activity. There are thousands of metabolites inside our cells, and surprisingly little is known about how most of them interact with other cellular components, even though when these interactions with proteins are disrupted, it can leave us more vulnerable to disease. New technology developed by U of U Health science faculty Jared Rutter, PhD, and Kevin Hicks, PhD, is changing that, allowing researchers to systematically identify which metabolites interact with particular proteins.

Rutter, Hicks, and their team used their platform, which they named MIDAS, to test for interactions between metabolites and the enzymes involved in carbohydrate metabolism. They found more than 800, many of which were previously unknown to researchers. With further experiments, they figured out exactly how several of the metabolites interact with enzymes to increase or dampen their activity. Their findings don’t just help explain how healthy cells work. By revealing specific ways in which metabolic pathways can be modulated, they suggest how drug developers might target the same pathways to treat disease. Atavistik, a company cofounded by Rutter, builds on this knowledge to explore potential treatments for cancer and metabolic diseases.

References:

Protein-metabolite interactomics of carbohydrate metabolism reveals regulation of lactate dehydrogenase. Hicks KG, Cluntun AA, Schubert HL, Hackett SR, Berg JA, Leonard PG, Ajalla Aleixo MA, Zhou Y, Bott AJ, Salvatore SR, Chang F, Blevins A, Barta P, Tilley S, Leifer A, Guzman A, Arok A, Fogarty S, Winter JM, Ahn H-C, Allen KN, Block S, Cardoso IA, Ding J, Dreveny I, Gasper C, Ho Q, Matsuura A, Palladino MJ, Prajapati S, Sun P, Tittmann K, Tolan DR, Unterlass J, VanDemark AP, Vander Heiden MG, Webb BA, Yun C-H, Zhap P, Wang B, Schopfer FJ, Hill CP, Nonato MC, Muller FL, Cox JE, and Rutter J. Science 2023 Mar 10;379(6636):996-1003. doi: 10.1126/science.abm3452.

Finding Inspiration for Drug Development in Metabolic Regulators | PI: Jared P. Rutter, PhD & Kevin Hicks, PhD

March 6, 2023March 27, 2025

Transferred Mitochondria Accumulate Reactive Oxygen Species, Promoting Proliferation

Cancer cells don’t act on their own. Their behavior is influenced by neighboring cells, which sometimes help them grow and spread. For instance, immune cells called macrophages patrol the body, engulfing and destroying potential threats. But when they interact with tumors, they can often produce signals that drive the disease. Scientists like U of U Health biochemist Minna Roh-Johnson, PhD, aim to learn how macrophages promote cancer’s growth and spread—a first step toward developing treatments that block those dangerous interactions.

Researchers in Roh-Johnson’s lab have uncovered a surprising way macrophages spur on cancer cells. She and her colleagues noticed that mitochondria—energy-generating structures inside cells—are often transferred from macrophages to tumor cells. While many scientists suspected the extra mitochondria might help fuel cancer cells, Roh-Johnson’s team saw something more complicated. Most of the transferred mitochondria couldn’t generate any energy at all—but they were surrounded by highly reactive metabolic byproducts called reactive oxygen species, which activated pathways that drive cell growth. Roh-Johnson notes that researchers have begun exploring the possibility of treating illness by delivering healthy mitochondria to damaged cells—suggesting it might one day be possible to manipulate these mitochondrial signals in cancer cells.

References:

Transferred mitochondria accumulate reactive oxygen species, promoting proliferation. Kidwell CU, Casalini JR, Pradeep S, Scherer SD, Greiner D, Bayik D, Watson DC, Olson GS, Lathia JD, Johnson JS, Rutter J, Welm AL, Zangle TA, Roh-Johnson M. Elife. 2023 Mar 6:12:e85494.

Press Releases and Media:

University of Utah Health: “We Need Everyone”: New Award Recognizes the Importance of Scientific Community

National Geographic

Transferred Mitochondria Accumulate Reactive Oxygen Species, Promoting Proliferation | PI: Minna Roh-Johnson, PhD

July 18, 2022March 27, 2025

Telehealth to Address Perinatal Depression

The debilitating sadness and anxiety of perinatal depression can strike during pregnancy or emerge in the weeks or months that follow. The condition, which affects up to 20 percent of pregnant women, can make even routine tasks and self-care a challenge, not to mention caring for an infant. Treatment with medication or psychotherapy usually helps, but most people with perinatal depression never receive the care they need. Connecting with doctors and therapists can be particularly difficult when clinics are far away, as is often the case in rural areas.

Recognizing how hard it can be for pregnant women and new moms to fit therapy into their lives, Gwen Latendresse, PhD, the College of Nursing’s Associate Director for Academic Programs, developed a way to bring therapy to them. Participants connect via videoconference once a week for an hourlong mindfulness-based cognitive behavioral therapy session. They evaluated the program in a study of 47 women who were experiencing or at high risk for perinatal depression and found that women welcomed the flexibility on-line therapy offered. After eight sessions, women at risk for perinatal depression remained stable, and those who began the program with depression showed an improvement in their symptoms. With these promising results, Latendresse is optimistic that telehealth can bring effective mental health support to all patients, regardless of where they are.

References:

Experiences with use of technology and telehealth among women with perinatal depression. Parameswaran UD, Pentecost R, Williams M, Smid M, Latendresse G. BMC Pregnancy Childbirth. 2022 Jul 18;22(1):571.

A Group Videoconference Intervention for Reducing Perinatal Depressive Symptoms: A Telehealth Pilot Study. Latendresse G, Bailey E, Iacob E, Murphy H, Pentecost R, Thompson N, Hogue C. J Midwifery Women’s Health. 2021 Jan;66(1):70-77.

Press Releases and Media:

University of Utah Health: “For the Love of Mothers”

U of U Health Key Faculty Collaborators:

Marcela Smid, MD, MS, MA (Dept. of Obstetrics & Gynecology)

Telehealth to Address Perinatal Depression | PI: Gwen Latendresse, PhD, RN

May 11, 2022May 30, 2025

Seeing the Light

Most of the world’s leading causes of blindness are conditions that damage the eye’s retina. Diabetes, genetic conditions, and aging can all cause the retina to deteriorate, leading to vision loss for millions of people. Because human eyes are so different from the eyes of mice and other animal models, these conditions have been difficult to study. But scientists at U of U Health have opened the door to studying the function of both healthy and diseased retinas in human eyes donated after death.

Neurons in the retina quickly stop signaling after a person dies. But Frans Vinberg, PhD, neuroscientist at the John A. Moran Eye Center, and collaborators have figured out how to protect and revive postmortem retinas so they can be used in research. Vinberg and his colleagues found that the loss of signaling in postmortem retinas came down to oxygen deprivation and changes in pH. If donated eyes could be collected quickly enough to prevent severe oxygen deprivation—which they found meant retrieving the tissue in the first half-hour after death—and stored in a solution with the right pH balance, they could restore the most essential function of cells in the retina: communicating with one another in response to light. The team’s approach has changed the way scientists study diseases that cause blindness and might one day bring scientists closer to making donated retinas viable for transplantation.

References:

Revival of light signalling in the postmortem mouse and human retina. Abbas, F., Becker, S., Jones, B. W., Mure, L. S., Panda, S., Hanneken, A., & Vinberg, F. Nature, 2022 Jun;606(7913):351-357. doi: 10.1038/s41586-022-04709-x.

Seeing the Light | PI: Frans Vinberg, PhD

March 29, 2022January 24, 2023

Illuminating the Mechanisms Behind Neuronal “Learning”

The strength of each of the thousands of synapses in a given neuron can be rapidly and independently modified in response to experience. What scientists do not yet understand is how distinct synapses distributed along neuronal processes—branches of a neuron which can project far from the cell body—are supplied with the appropriate type and number of neurotransmitter receptors. Previous studies from the laboratory of University of Utah Health scientist Andres Villu Maricq, MD, PhD, provided insight into this problem by showing that the delivery and removal of AMPA-type ionotropic glutamate receptors (AMPARs) to and from synapses depends on transport by kinesin protein motors.

More recently, Maricq and colleagues have demonstrated that the coordinated activities of two major signaling pathways converge on a complex of scaffold proteins to regulate the loading of AMPAR cargo onto kinesin motors, thereby providing a mechanism to explain the rapid exchange of AMPARs in response to synaptic activity. These findings reveal mechanisms underlying the control of cellular transport, and have important implications for cellular models of learning and memory.

References:

MAPK signaling and a mobile scaffold complex regulate AMPA receptor transport to modulate synaptic strength. Hoerndli FJ, Brockie PJ, Wang R, Mellem JE, Kallarackal A, Doser RL, Pierce DM, Madsen DM, Maricq AV. Cell Reports. 2022 Mar 29;38(13):110577.

Illuminating the Mechanisms Behind Neuronal “Learning” | PI: Andres Villu Maricq, MD, PhD

March 8, 2022December 15, 2022

Opposite-Sex Parent’s Genetic Impact on Health and Behavior

Parenting is not the only way moms and dads impact the behavior of their offspring. Genes matter, too. Most of our genes are inherited in pairs—one copy from each parent. However, according to new research from the lab of University of Utah Health researcher Christopher Gregg, PhD, each parent has their own genetic impact on hormones and neurotransmitters that control mood and behavior. Catecholamines, including dopamine, noradrenaline and adrenaline, are hormones that have important effects on depression, addiction, obesity, and other major medical conditions. The Gregg lab made the surprising discovery that the maternally and paternally inherited gene copies of the enzymes that make catecholamines play different roles in offspring. The mother’s gene copy is activated in specific brain cells, and the father’s is active in subsets of cells in the adrenal gland. The study used new computer algorithms that make hundreds of measurements, finding that the mother’s gene copy affects specific behaviors and hormones in sons, while the father’s gene copy affects daughters. This study reveals important parental controls over sons and daughters.

References:

Noncanonical genomic imprinting in the monoamine system determines naturalistic foraging and brain-adrenal axis functions. Bonthuis PJ, Steinwand S, Stacher Hörndli CN, Emery J, Huang WC, Kravitz S, Ferris E, Gregg C. Cell Reports. 2022 Mar 8;38(10):110500.

Press Releases and Media:

University of Utah Health: “Parental Control: How Genes from Mom or Dad Shape Behavior”

The Scientist
ABC4

Opposite-Sex Parent’s Genetic Impact on Health and Behavior | PI: Christopher T. Gregg, PhD

January 18, 2022February 28, 2025

Teasing Apart Effects of Comorbid Conditions on Cardiovascular Health

Understanding the complex clinical variables that drive cardiovascular health outcomes in patients with multiple conditions poses a major challenge for personalized medicine. University of Utah Health researchers Karen Eilbeck, PhD, Martin Tristani-Firouzi, MD, and Mark Yandell, PhD, recently developed and deployed a massively scalable comorbidity discovery method to analyze electronic health records (EHRs) from the University of Utah and Primary Children’s Hospital (over 1.6 million patients and 77 million visits) for comorbid diagnoses, procedures, and medications. Using artificial intelligence, they tease apart the intertwined impacts of patients’ comorbid conditions and demographic characteristics upon cardiovascular health outcomes, focusing on the key areas of heart transplant, sinoatrial node dysfunction, and various forms of congenital heart disease.

The resulting “multimorbidity networks” enable wide-ranging exploration of the comorbid and demographic factors in cardiovascular outcomes, and can be distributed as web-based tools for further community-based health research.

The ability to transform enormous collections of EHRs into compact, portable tools devoid of Protected Health Information solves many of the legal, technological, and data-scientific challenges associated with large-scale EHR analyses.

References:

An explainable artificial intelligence approach for predicting cardiovascular outcomes using electronic health records. Wesołowski S, Lemmon G, Hernandez EJ, Henrie A, Miller TA, Weyhrauch D, Puchalski MD, Bray BE, Shah RU, Deshmukh VG, Delaney R, Yost HJ, Eilbeck K, Tristani-Firouzi M, Yandell M. PLOS Digital Health. 2022;1(1):e0000004.

Press Releases and Media:

University of Utah Health: “Artificial Intelligence Identifies Individuals at Risk for Heart Disease Complications”

Genetic & Engineering News
Utah Business
Healthcare IT News

U of U Health Key Faculty Collaborators:

Joseph Yost, PhD

Teasing Apart Effects of Comorbid Conditions on Cardiovascular Health | PI: Mark Yandell, PhD, Martin Tristani-Firouzi, MD & Karen Eilbeck, PhD

October 15, 2021April 4, 2023

Engineered Human Juvenile Chondrocyte Sheets Safely Repair Damaged Cartilage

The body cannot heal damage to cartilage, and such defects eventually progress to joint osteoarthritis, impacting more than 5.6 million Americans. Current approaches to repairing cartilage have issues in the quality of the repaired tissue, potential treatment variability, costs, and long wait times for patients. University of Utah Health researcher Makoto Kondo, PhD, and colleagues combined two cutting-edge methods to address these issues: (1) cell sheet technology, which generates sheets of cells to replace or repair damaged tissue; and (2) human juvenile chondrocyte sourcing, which harvests juveniles’ cartilage-generating cells (more active than adults’) from otherwise-discarded surgical byproducts. Early research has demonstrated the safety and efficacy of the engineered juvenile chondrocyte sheets. The juvenile cells generated tissue quickly, permitting large-scale production of cell sheets. Transplanting the sheets into rats with cartilage damage led to cartilage regeneration and rapid functional recovery. This approach overcomes the issues of other therapeutic options, enabling reliable and sustainable regenerative treatment for cartilage injuries. Further research will examine the complicated regenerative mechanism behind this method’s success and pioneer its application in humans.

References:

Safety and efficacy of human juvenile chondrocyte-derived cell sheets for osteochondral defect treatment. Kondo M, Kameishi S, Kim K, Metzler NF, Maak TG, Hutchinson DT, Wang AA, Maehara M, Sato M, Grainger DW, Okano T. npj Regenerative Medicine. 2021 Oct 15;6(1):65.

Novel therapies using cell sheets engineered from allogeneic mesenchymal stem/stromal cells. Kondo M, Kameishi S, Grainger DW, Okano T. Emerging Topics in Life Sciences. 2020 Dec 17;4(6):677-689.

U of U Health Key Faculty Collaborators:

Travis Maak, MD, Department of Orthopaedics
Jeffrey Weiss, PhD, Department of Biomedical Engineering
David Grainger, PhD, Department of Biomedical Engineering and Molecular Pharmaceutics
Teruo Okano, PhD, Department of Molecular Pharmaceutics

Engineered Human Juvenile Chondrocyte Sheets Safely Repair Damaged Cartilage | PI: Makoto Kondo, PhD

October 14, 2021December 20, 2022

A Protein that Blocks Virus Budding

HIV and other enveloped viruses wrap themselves in the cell’s external membrane exterior, forming buds. They are then released from cells using membrane-cutting machinery (called the ESCRT pathway) that they “steal” from the cell. This broad dependence upon the ESCRT pathway provides a potential target for blocking the replication of many different viruses. However, cells depend on the ESCRT pathway to perform critical functions, meaning that ESCRT-blocking strategies can also be toxic for cells.

A collaboration between the labs of University of Utah Health researchers Nels Elde, PhD, and Wesley Sundquist, PhD, showed that some mammals contain duplicated and shortened genes for a key ESCRT protein. The resulting “retroCHMP3” proteins block the release of HIV and other enveloped viruses. Remarkably, retroCHMP3 proteins from primates and mice appear to work by delaying ESCRT processes, causing extreme damage to HIV and other viruses but little harm to cells. This discovery creates the possibility of engineering retroCHMP3 mice and testing whether they are broadly protected against enveloped viruses, with the long-term goal of finding new ways to target the ESCRT pathway to counter viral infections.

References:

RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis. Rheinemann L, Downhour DM, Bredbenner K, Mercenne G, Davenport KA, Schmitt PT, Necessary CR, McCullough J, Schmitt AP, Simon SM, Sundquist WI, Elde NC. Cell. 2021 Oct 14;184(21):5419-5431.e16.

Press Releases and Media:

University of Utah Health: “Gene found in monkeys and mice could work as a new type of antiviral to block HIV, Ebola, and other deadly viruses in humans“

Genetic Engineering & Biotechnology News
Daily Mail

A Protein that Blocks Virus Budding | PI: Wesley I. Sundquist, PhD & Nels C. Elde, PhD