Researchers at University of Utah Health (U of U Health) have discovered that fatty molecules called ceramides initiate AKI by damaging the mitochondria that supply energy to kidney cells. By using a backup drug candidate designed to alter how ceramides are processed, the team protected mitochondrial structure and prevented kidney injury in mice.

“We completely reversed the pathology of acute kidney injury by inactivating ceramides,” says Scott Summers, PhD, distinguished professor and Chair of the Department of Nutrition and Integrative Physiology in the University of Utah College of Health and senior author on the study. “We were stunned — not only did kidney function stay normal, but the mitochondria were unscathed,” Summers says. “It was truly remarkable.”

The results are published in Cell Metabolism.

Ceramide spikes may serve as an early warning

Earlier studies from the Summers lab showed that ceramides can harm organs such as the heart and liver. When the researchers measured ceramides in AKI models, they found a strong connection: levels rose sharply after injury in both mice and in human urine samples.

“Ceramide levels are very elevated in kidney injury,” says Rebekah Nicholson, PhD, first author on the work, who completed the research as a graduate student in nutrition and integrative physiology at U of U Health and is now a postdoctoral fellow at the Arc Institute. “They go up quickly after damage to the kidneys, and they go up in relation to the severity of the injury. The worse the kidney injury is, the higher the ceramide levels will be.”

These findings indicate that urinary ceramides could act as an early biomarker for AKI, giving clinicians a tool to identify vulnerable patients, including those preparing for heart surgery, before symptoms begin. “If patients are undergoing a procedure that we know puts them at high risk of AKI, then we can better predict whether or not they’re actually going to have one,” Nicholson says.

Altering ceramide production protects kidney function

The team nearly eliminated kidney injury in a mouse model by modifying the genetic program that controls ceramide production. This change produced “super mice” that did not develop AKI even under conditions that typically cause severe damage.

The researchers then tested a ceramide-lowering drug candidate created by Centaurus Therapeutics, a company co-founded by Summers. Mice treated ahead of time avoided kidney injury, maintained normal kidney function, remained active, and had kidneys that appeared close to normal under the microscope. Nicholson notes that their model places extreme stress on the kidneys, making it “really remarkable that mice were protected from the injury.”

“These mice looked incredible,” Summers adds.

The team found that ceramides harm mitochondria, the parts of the cell responsible for energy production. Damaged mitochondria in kidney cells become distorted and function poorly. Adjusting ceramide production, whether genetically or with the drug, kept mitochondria intact and working even under strain.

Potential for future therapies targeting mitochondrial health

Summers explains that the compound used in this study is closely related to, but not identical to, the ceramide-lowering drug that has entered human clinical testing. He emphasizes that mouse results do not always predict human outcomes and that further research is needed to confirm safety.

“We’re thrilled by how protective this backup compound was, but it’s still preclinical,” Summers says. “We need to be cautious and do our due diligence to make sure this approach is truly safe before moving it into patients.”

Even so, the researchers are encouraged by the findings. If the results extend to people, the drug could potentially be administered ahead of time to individuals who face a high risk of AKI, including patients undergoing heart surgery, where about one quarter experience the condition.

Because the drug appears to work by maintaining mitochondrial health, the team believes that the approach may have relevance for other disorders linked to mitochondrial dysfunction.

“Mitochondrial problems show up in so many diseases — heart failure, diabetes, fatty liver disease,” Summers says. “So if we can truly restore mitochondrial health, the implications could be enormous.”

The results are published in Cell Metabolism as “Therapeutic Remodeling of the Ceramide Backbone Prevents Kidney Injury.”

Funding and disclosures

This work was supported by a NCRR Shared Instrument Grant, the Kidney Precision Medicine Project, and several branches of the National Institutes of Health, including the National Cancer Institute (P30CA042014, CA272529), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115824, DK116888, DK116450, DK130296, DK108833, DK112826, 1F31DK134088 and 5T32DK091317), and the National Institute of General Medical Sciences (3R35GM131854 and 3R35GM131854-04S1). Additional support came from the Juvenile Diabetes Research Foundation (JDRF 3-SRA-2019-768-A-B and JDRF 3-SRA-2019-768-A-B to WLH), the Burroughs Wellcome Fund Postdoctoral Diversity Enrichment Program (1058616), the American Diabetes Association, the American Heart Association, the Margolis Foundation, and the University of Utah Diabetes and Metabolism Research Center. The authors state that the content is their responsibility and does not necessarily reflect the views of the National Institutes of Health.

Scott Summers and Jeremy Blitzer are co-founders and shareholders of Centaurus Therapeutics. Liping Wang is also a shareholder. DN and Blitzer are listed as inventors on US Patents 1177684, 11597715, and 11135207 licensed to Centaurus Therapeutics, Inc.

The project was organized by Tamás Hajdu (Department of Anthropology, Faculty of Sciences, Eötvös Loránd University (ELTE TTK)), with genetic analyses conducted by Anna Szécsényi-Nagy and Noémi Borbély of the Institute of Archaeogenomics, ELTE RCH. Their work demonstrates how historical accounts can be validated and violent deaths reconstructed in remarkable detail when the humanities and natural sciences collaborate. The study has been published in Forensic Science International: Genetics.

Early Discoveries on Margaret Island

The story began in 1915, when archaeologists excavating the Dominican monastery on Margaret Island (Budapest) uncovered the bones of a young man in the sacristy. Based on the burial context, period sources, and the evidence of trauma on the skeleton, researchers at the time suggested that the remains belonged to Béla Duke of Macsó, a member of the House of Árpád. Béla of Macsó (born after 1243 — died: November 1272) was the grandson of King Béla IV on his mother’s side, while his father’s lineage traced back to the Rurik dynasty of northern, Scandinavian origin, which produced numerous Grand Dukes of Kiev from the 9th century onward. According to 13th-century Austrian chronicles, Duke Béla was assassinated in November 1272 by Ban Henrik “Kőszegi” of the Héder family and his associates. Contemporary stories describe how his mutilated body was collected by Margit (his sister) and Erzsébet (his niece) and buried at the Dominican monastery.

Lost Bones and a 20th-Century Disappearance

After the excavation, the remains were sent to Lajos Bartucz at the Institute of Anthropology of the Budapest University (now: Department of Anthropology, ELTE TTK) for bioanthropological study. Bartucz documented 23 sword cuts across the skeleton, along with multiple fatal skull injuries. He concluded that the duke had been attacked by several individuals simultaneously and had even been struck while lying on the ground. Bartucz mentioned the bones publicly in 1936 and published a photograph of the skull in 1938. After that, all references to the remains disappeared, and many experts believed they had been lost during the Second World War. Unexpectedly, in 2018 the postcranial bones were rediscovered in a wooden box stored among tens of thousands of specimens in the Anthropology Collection of the Hungarian Museum of Natural History, while the skull continued to be curated in the Aurél Török Collection at ELTE.

Reopening the Case With Modern Science

In 2018, a new international research consortium was formed under the leadership of Tamás Hajdu (Department of Biological Anthropology, ELTE TTK). The group included anthropologists, geneticists, an archaeologist, an archaeobotanist, stable isotope specialists, radiocarbon experts, and dentists. Their objective was to verify the identity of the remains using modern forensic and bioarchaeological methods and to reconstruct as fully as possible the life and death of the duke.

The find holds exceptional historical value. Besides King Béla III, Béla of Macsó is the only confirmed member of the House of Árpád whose nearly complete skeleton is still preserved. This provides rare insight into both the genetic heritage of the Árpád dynasty and the Rurik line. Researchers from Vienna, Bologna, Helsinki, Harvard University, and multiple Hungarian institutions participated in the project.

Biological Profile and Diet Insights

Anthropological analysis showed that the man buried beneath the monastery floor on Margaret Island was in his early twenties. Radiocarbon dating was performed by two laboratories to ensure accuracy after early 14C measurements suggested a date slightly earlier than expected (second half of the 13th century). Additional tests by the Nuclear Research Institute (Debrecen) revealed that the unexpectedly early date was caused by dietary habits. The individual had consumed high amounts of animal protein, including fish and possibly shellfish that fed on ancient carbon sources, creating a known “reservoir” effect in the bones.

The team also examined dental calculus to further reconstruct his diet. More than a thousand microfossils were recovered from the tartar. Starch grains from wheat and barley, along with clear signs of milling, cooking, and baking, indicated that his meals included cooked wheat semolina and baked wheat bread.

Strontium isotope analysis, which helps determine where a person lived during different stages of life, showed that the individual did not grow up in the same place where he was buried. His early childhood isotope signatures match those found in the region of Vukovar and Syrmia (now part of Croatia and Serbia; earlier this region was a part of the Macso Banat of the Medieval Kingdom of Hungary), as well as other parts of the Carpathian Basin. Later in childhood he moved to a different area, possibly near modern Budapest.

Genetic Evidence Links the Skeleton to Royal Lineages

The final confirmation of identity was carried out at the Institute of Archaeogenomics of ELTE RCH by Anna Szécsényi-Nagy and Noémi Borbély. Multiple lines of genetic evidence supported the genealogical connections described in historical documents. The results show that Béla of Macsó was the great-grandson (fourth-degree descendant) of King Béla III, and his genetic distance to Saint Ladislaus fits this expected lineage pattern.

Genome-wide analysis revealed that the duke had a strong Scandinavian genetic component (almost half), significant Eastern Mediterranean ancestry, and a smaller early medieval Central European component. The Scandinavian contribution supports his descent from the Rurik dynasty, while the Eastern Mediterranean component may correspond to his maternal grandmother, Maria Laskarina, a member of the Byzantine imperial family and wife of Béla IV. Y-chromosome results also confirm the historically documented Rurik paternal line. A 2023 Russian archaeogenomic study showed that a 13th-century Rurikid (Dmitry Alexandrovich) belonged to the same paternal lineage, which can be traced back to Yaroslav I (Yaroslav Vladimirovich, also known as Yaroslav the Wise). Genetic data from present-day Rurikid descendants further reinforces this connection.

Reconstructing a Coordinated and Brutal Assassination

To understand how Béla died and to compare the evidence with medieval accounts, the team conducted a detailed forensic anthropological investigation. The analysis documented 26 perimortem injuries, including nine to the skull and 17 to the rest of the body, all inflicted during a single violent attack. The pattern of wounds suggests that three assailants took part: one confronted him from the front while the others struck from the left and right.

The wounds show that Béla recognized the attack and tried to defend himself. Two types of weapons were likely used, probably a sabre and a longsword. The depth and clarity of the cuts indicate that he wore no armor when he was killed. The reconstructed sequence of violence begins with strikes to the head and upper body, followed by severe defensive injuries as he attempted to block further blows. He was ultimately incapacitated by strikes from the side, and once he fell to the ground, the attackers delivered fatal blows to his head and face. The number and intensity of these injuries point to strong emotional motivation (e.g. sudden anger, hatred), while the coordinated nature of the attack suggests planning. Although Duke Béla’s assassination in November 1272 appears to have been partly or wholly premeditated, the manner of the killing indicates that it was not carried out calmly.

Researchers and institutions participating in the research project:

• Tamás Hajdu coordinator of the project, first author: Department of Biological Anthropology at ELTE, Budapest and Centre for Applied Bioanthropology, Institute for Anthropological Research, Zagreb, Croatia
• Noémi Borbély, corresponding author: Institute of Archaeogenomics, ELTE RCH, Budapest and Doctoral School of Biology at ELTE
• Zsolt Bernert and Ágota Buzár: Hungarian Natural History Museum, Budapest
• Tamás Szeniczey: Department of Biological Anthropology at ELTE, Budapest
• István Major, Mihály Molnár, Anikó Horváth, László Palcsu and Zsuzsa Lisztes-Szabó: Isotope Climatology and Environmental Research Centre, HUN-REN Institute for Nuclear Research, Debrecen
• Zsuzsa Lisztes-Szabó: Department of Botany, Faculty of Science and Technology, University of Debrecen, Debrecen
• Claudio Cavazzuti: Department of History and Culture, Alma Mater Studiorum, University of Bologna, Bologna, Italy
• Barna Árpád Kelentey and János Angyal: Faculty of Dentistry, University of Debrecen, Debrecen
• Balázs Gusztáv Mende and Kristóf Jakab: Institute of Archaeogenomics, ELTE RCH, Budapest
• Takács Ágoston: Medieval Department, Castle Museum — Budapest History Museum, Budapest
• Olivia Cheronet and Ron Pinhasi: Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.
• David Emil Reich: Department of Genetics, Harvard Medical School, Boston, USA, Department of Human Evolutionary Biology, Harvard University, Cambridge, USA, Broad Institute of MIT and Harvard, Cambridge, USA és Howard Hughes Medical Institute, Boston, USA
• Martin Trautmann, correspondig author: Department of Cultures/Archaeology, University of Helsinki, Helsinki, Finland és A und O — Anthropologie und Osteoarchäologie Praxis für Bioarchäologie, München
• Anna Szécsényi-Nagy, last author: Institute of Archaeogenomics, ELTE RCH, Budapest

“It really shrinks the planet,” says Professor Nicholaus Parziale, whose work centers on turning hypersonic travel from aspiration into reality. Parziale recently received the Presidential Early Career Award for Scientists and Engineers in recognition of his research into fluid mechanics at extreme speeds. “It will make travel faster, easier and more enjoyable.”

The Challenges of Flying at Mach 10

Covering half the world in just one hour may seem impossible, yet the technology is not as far away as it appears. Some military aircraft already reach speeds of Mach 2 or Mach 3, which means two or three times the speed of sound. Mach 1 equals about 760 miles per hour. To travel from Los Angeles to Sydney in sixty minutes, an aircraft would need to reach Mach 10. The major obstacles are the extraordinary turbulence and heat produced during flight at these extreme speeds.

There is a fundamental difference between how air behaves around an aircraft at lower speeds and how it behaves at higher speeds. Engineers describe these conditions as incompressible flow and compressible flow. In incompressible flow, which occurs at lower speeds (below about Mach 0.3 or 225 miles per hour), the density of the air stays nearly the same. This consistency simplifies aeronautical design. Once an aircraft moves faster than the speed of sound, the airflow becomes compressible instead. “That’s because a gas can ‘squish,'” Parziale explains, meaning it can compress.

Why Airflow Behavior Matters for Hypersonic Design

When air compresses, its density changes in response to variations in both pressure and temperature. These shifts influence how an aircraft interacts with the air around it. “Compressibility affects how the airflow goes around the body and that can change things like lift, drag, and thrust required to take off or stay airborne.” All of these factors play a major role in aircraft design.

Engineers already understand airflow fairly well for aircraft that fly below or near the speed of sound, a range called “low Mach” numbers. Creating hypersonic aircraft requires a much deeper understanding of how air behaves at Mach 5, Mach 6, or even Mach 10. Much of that behavior is still uncertain, except for guidance provided by Morkovin’s hypothesis.

Morkovin’s Hypothesis and the Mystery of Hypersonic Turbulence

Developed by Mark Morkovin in the mid 20th century, the hypothesis proposes that when air moves around Mach 5 or Mach 6, the fundamental nature of turbulence remains surprisingly similar to turbulence at lower speeds. Although high-speed airflow involves larger shifts in temperature and density, Morkovin suggested that the general pattern of turbulent motion stays mostly consistent. “Basically, the Morkovin’s hypothesis means that the way the turbulent air moves at low and high speeds isn’t that different,” Parziale says. “If the hypothesis is correct, it means that we don’t need a whole new way to understand turbulence at these higher speeds. We can use the same concepts we use for the slower flows.” This also suggests that future hypersonic aircraft may not require a completely different design philosophy.

Despite its importance, the hypothesis has lacked solid experimental validation. That gap led to Parziale’s recent research, described in his study Hypersonic Turbulent Quantities in Support of Morkovin’s Hypothesis, published in Nature Communications on November 12, 2025.

A Laser and Krypton Experiment Eleven Years in the Making

In the study, Parziale’s team introduced krypton gas into a wind tunnel and used lasers to ionize it. This process briefly created a straight, glowing line formed by the krypton atoms. High-resolution cameras then captured how this illuminated line bent, twisted, and distorted as it moved through the airflow, similar to how a leaf drifts and spins within small swirling currents in a river.”As that line moves with the gas, you can see crinkles and structure in the flow, and from that, we can learn a lot about turbulence,” Parziale says. He notes that developing the experimental setup required 11 years of effort. “And what we found was that at Mach 6, the turbulence behavior is pretty close to the incompressible flow.”

Parziale’s group received early support from the Air Force Office of Scientific Research Young Investigator Research Program (YIP) in 2016 and from the Office of Naval Research (ONR) YIP in 2020, with the latest work also funded by ONR.

What the Findings Mean for Future Flight and Space Access

While Morkovin’s hypothesis is not yet completely proven, the new results move scientists closer to understanding how to design aircraft that can withstand hypersonic speeds. The findings indicate that engineers may not need to reinvent the fundamental approach to aircraft design for these extreme conditions, which simplifies the challenge significantly.

“Today, we must use computers to design an airplane, and the computational resources to design a plane that will fly at Mach 6, simulating all the tiny, fine, little details would be impossible,” Parziale explains. “The Morkovin’s hypothesis allows us to make simplifying assumptions so that the computational demands to design hypersonic vehicles can become more doable.”

Parziale adds that the same principles could transform future access to space. “If we can build planes that fly at hypersonic speed, we can also fly them into space, rather than launching rockets, which would make transportation to and from low Earth orbit easier,” he says. “It will be a game-changer for transportation not only on earth, but also in low orbit.”