ROCHESTER, Minn. — Researchers have validated a genetic scoring tool that may help physicians diagnose idiopathic pulmonary fibrosis and identify which patients are at greatest risk for severe outcomes, including death or the need for a lung transplant. The findings come from a new international study of more than 570,000 people co-led by Mayo Clinic and Brigham and Women's Hospital.

Published in the American Journal of Respiratory and Critical Care Medicine, the study is one of the largest real-world evaluations of a polygenic risk score for idiopathic pulmonary fibrosis. The findings bring this genomic approach one step closer to clinical care.

"Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

- Dr. Victor Ortega

Researchers analyzed genomic and electronic health record data from four major biobanks in the U.S. and U.K., including the Mayo Clinic Biobank and Mayo Clinic Tapestry. They calculated a polygenic risk score for each participant by combining the effects of more than 60,000 DNA variants associated with idiopathic pulmonary fibrosis. While each genetic variant contributes only a small amount of risk, together they reveal patterns of inherited susceptibility that would otherwise be difficult to detect.

The researchers then tested whether the score could identify patients with the disease and predict clinical outcomes.

People with high polygenic risk scores were nearly three times more likely to have the disease than those with lower scores. The genetic score became even more predictive as researchers applied increasingly specific definitions of the disease, suggesting the score may one day help distinguish idiopathic pulmonary fibrosis from other forms of interstitial lung disease.

Among patients with the disease, those with high genetic risk were 23% more likely to die or require a lung transplant, indicating the score may also help identify patients at greatest risk of poor outcomes.

"Every patient has a unique genetic blueprint that we can use to estimate risk for the development of disease," says Victor Ortega, M.D., Ph.D., a pulmonologist, associate director of Mayo Clinic's Center for Individualized Medicine in Arizona, and a co-senior author of the study. "Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

"Showing that this approach works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

- Dr. Christopher Grilli

Idiopathic pulmonary fibrosis causes irreversible scarring of the lungs that progressively limits a person's ability to breathe. More than 100,000 Americans are living with the disease, and an estimated 30,000 to 40,000 new cases are diagnosed each year, according to the National Institutes of Health.

Because its symptoms often resemble those of other interstitial lung diseases, diagnosis can be delayed until significant, irreversible lung damage has already occurred. Confirming the diagnosis sometimes requires an invasive lung biopsy to collect lung tissue. Researchers hope a noninvasive genetic test using DNA from a blood or saliva sample may help reduce the need for those procedures in selected patients.

"Most polygenic risk scores are developed in carefully selected research populations," says Christopher Grilli, Pharm.D., a researcher at Mayo Clinic's Center for Individualized Medicine and co-first author of the study. "Showing that this approach also works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

If further validated, researchers envision genomic risk scores complementing imaging and other diagnostic tools to help physicians diagnose the disease with greater confidence.

This research aligns with Mayo Clinic's Precure Research initiative, which seeks to uncover the earliest biological changes associated with disease and translate those discoveries into clinical tools that improve diagnosis, personalize care and ultimately change the course of disease. As part of that effort, the Precure-Lung study, led by Dr. Ortega, is expanding Mayo Clinic's research into interstitial lung diseases, including idiopathic pulmonary fibrosis.

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:  

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post Researchers chart a genetic path to diagnosing pulmonary fibrosis and predicting outcomes appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A new Mayo Clinic study shows that integrating telomere length evaluation and genetic testing into pulmonary care can significantly change how physicians diagnose and treat pulmonary fibrosis — in some cases even redirecting the course of care.

Telomeres are protective caps at the ends of chromosomes — the structures that carry a person's DNA. They naturally shorten as people age, but in some inherited conditions, they become unusually short. This shortening has been linked to certain forms of pulmonary fibrosis, a group of diseases that cause progressive scarring in the lungs and make breathing increasingly difficult.

In the study of 66 patients, nearly 1 in 5 had a disease-causing genetic variant, and results from testing changed clinical care in more than half of patients. The results were published in Mayo Clinic Proceedings.

"These diseases are often difficult to diagnose, and patients may be treated based on incomplete or unclear underlying causes," says Kathryn del Valle, M.D., a Mayo Clinic pulmonologist and lead author of the study.

To address this challenge, researchers paired genetic testing with telomere length measurement. Together, these tools helped uncover hidden drivers of disease and guide more precise management decisions.

"This work demonstrates a practical, scalable way to incorporate genetic and telomere assessment into clinical care for patients with fibrotic interstitial lung disease," says Eva Carmona, M.D., Ph.D., a Mayo Clinic pulmonologist and senior author.

The additional insights from testing led to meaningful changes in care, including the evaluation of comorbidities, medication adjustments, referrals to specialized clinics and earlier consideration of lung transplant. The information can also help clinicians avoid treatments and procedures that may be ineffective — or even harmful — in patients with certain genetic or telomere-related conditions.

"Genetic and telomere testing may help elucidate why disease is occurring, guide management decisions and identify family members who may be at risk," Dr. Carmona says.

Beyond individual patients, the findings have important implications for families. Identifying a genetic cause can help flag relatives who may be at risk, allowing them to pursue earlier screening, genetic counseling and testing.

Mayo Clinic plans to expand this model and launch a Familial Pulmonary Fibrosis Clinic to further coordinate genetic testing, counseling and comprehensive care for patients and at-risk relatives.

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and to providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post Genetic testing changes care for pulmonary fibrosis patients appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have created a detailed map of the pulvinar, a deep brain region that could help doctors more precisely target brain stimulation therapies for people with drug-resistant epilepsy.

The findings, published in the Journal of Neuroscience, reveal that brain regions separated by only a few millimeters connect to entirely different brain networks. The discovery provides a blueprint for placing electrodes more precisely during deep brain stimulation, an emerging treatment for epilepsy.

The researchers studied people with drug-resistant epilepsy who already had temporary electrodes implanted as part of their clinical care. By delivering small electrical pulses to different parts of the pulvinar and measuring the brain's responses, the team created a map showing how this largely unexplored region communicates with the rest of the brain.

The pulvinar is part of the thalamus, a deep brain structure that relays and coordinates information from sight, sound, touch and other senses. Because it lies deep within the brain, scientists have had limited opportunities to study how its different regions connect to other brain networks.

"We were surprised by how large, detailed and complex this deep brain structure is, and by its potential role in guiding epilepsy treatments," says Dora Hermes Miller, Ph.D., a biomedical engineer at Mayo Clinic and senior author of the study.

The findings have immediate relevance for clinical care and build upon ongoing research to develop personalized treatment for people with drug-resistant epilepsy. "We are already using the pulvinar maps to help individualize pulvinar deep brain stimulation targeting in patients with drug-resistant epilepsy, while continuing to study how these maps relate to long-term outcomes," says co-author Nick Gregg, M.D., a neurologist at Mayo Clinic.

Why researchers studied the pulvinar

Researchers recognized the pulvinar's therapeutic potential when they were caring for patients with drug-resistant epilepsy. As part of their clinical care, patients had electrodes placed in several brain regions, including the pulvinar, to evaluate whether stimulation could reduce seizures.

"When we stimulated the pulvinar, we expected to see the same brain networks respond each time," Dr. Hermes says. "Instead, some patients showed activation of visual brain areas while others didn't. That unexpected finding led us to ask why."

By studying 30 patients, the researchers discovered that the pulvinar is not a single, uniform structure. Instead, it contains specialized regions connected to different brain networks involved in vision, memory, language and attention.

The distances between these pulvinar subregions were remarkably small. Brain regions separated by as little as 3 millimeters connected to completely different brain networks.

"That level of detail means that if neurologists want to suppress the seizures coming from those areas, they have to place electrodes in the precise right spot. And these findings provide a guide towards that spot," Dr. Hermes says.

What the study means for personalized epilepsy treatments

Epilepsy affects more than 50 million people worldwide. About one-third continue to have seizures despite medication. For many of these patients, neuromodulation — a treatment that uses electrical stimulation to regulate brain activity — can help reduce seizures.

"These findings provide data that enables exploration of tailoring neuromodulation therapies in a more personalized way, targeting each patient's specific epilepsy networks," says Gregory Worrell, M.D., Ph.D., a study co-author and neurologist at Mayo Clinic.

Researchers are now investigating which parts of the pulvinar should be stimulated — and at what frequencies — to better control seizures while minimizing side effects.

"Our aim is to make therapy more precise, more consistent and ultimately more effective," Dr. Gregg says.

The study highlights the collaborative mission of Mayo Clinic's Bioelectronic Neuromodulation Innovation to Cure (BIONIC) initiative, which unites clinicians, scientists and engineers to translate advances in brain science into personalized neuromodulation therapies.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic study identifies new brain targets for individualized epilepsy treatment appeared first on Mayo Clinic News Network.

Mayo Clinic’s Berg Innovation Exchange and Business Development unite expertise in collaboration, commercialization and venture creation to accelerate innovation worldwide

ROCHESTER, Minn. — Mayo Clinic is strengthening its commitment to advancing healthcare innovation by aligning the Mayo Clinic Berg Innovation Exchange with Mayo Clinic Business Development, creating new opportunities to help promising discoveries reach patients and communities worldwide.

Since its launch, the Berg Innovation Exchange has connected innovators with expertise, mentorship and a global network of collaborators. The exchange has served as a catalyst for innovation within Mayo Clinic and across the broader healthcare ecosystem, bringing together clinicians, researchers, entrepreneurs, industry leaders and investors to explore new approaches to healthcare challenges.

The alignment with Business Development creates stronger connections between early-stage innovation activities and the expertise needed to advance technologies, launch new ventures and expand the reach of Mayo Clinic discoveries.

"From the beginning, the vision of the exchange has been to help innovators find the expertise and opportunities needed to move ideas forward," says Jennie Kung, vice chair of Mayo Clinic Berg Innovation Exchange. "What started as a vision for accelerating innovation has grown into a community of innovators and problem-solvers and positions us to support even more meaningful work in the years ahead."

The exchange helps innovators refine and validate new concepts by providing access to collaborators’ collective expertise. Business Development complements those efforts through capabilities in intellectual property, licensing, venture creation, investment activities and commercialization.

Together, these capabilities create a more seamless pathway from discovery to real-world application, helping promising innovations advance toward broader adoption and patient impact.

"Innovation depends on strong connections between discovery, commercialization and collaboration," says Andy Danielsen, chief business development officer at Mayo Clinic. "This alignment expands opportunities to work with organizations around the world and provides the resources needed to translate ideas into products and services that benefit patients."

As healthcare continues to evolve, Mayo Clinic is committed to fostering relationships and collaborations that help advance innovation beyond institutional boundaries. Earlier access to expertise and strategic guidance can help innovators navigate key decisions and identify the most effective path forward.

"The ultimate measure of innovation is whether it makes a difference in people's lives," says Peter Noseworthy, M.D., medical director for Business Development. "Strengthening the connection between innovation and commercialization helps promising discoveries gain traction beyond Mayo Clinic and creates more opportunity for impact."

The exchange will continue to play an important role in identifying opportunities, encouraging collaboration and helping innovators transform promising ideas into meaningful advances.

At its core, the effort reflects Mayo Clinic's belief that meaningful progress happens when people with diverse expertise come together to solve important challenges.

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About the Berg Innovation Exchange
Supported by philanthropic funding, the Berg Innovation Exchange operates with impartiality, ensuring equal opportunities for all innovators and stakeholders, with an emphasis on addressing healthcare needs over individual or institutional interests.

About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tom Millikin, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic strengthens innovation ecosystem to advance discoveries from ideas to patient impact appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A multi-center study, co-led by researchers at Mayo Clinic and Michigan State University, found that patients who received tranexamic acid during liver surgery were three times less likely to develop post-hepatectomy liver failure than patients who received a placebo. The findings were published in Blood.

Post-hepatectomy liver failure is one of the most serious complications following liver surgery and remains a leading cause of death after liver resection. Currently, there are no approved medications specifically designed to prevent this complication.

The findings provide both mechanistic and clinical evidence that targeting the body's fibrinolytic system — which helps break down blood clots — may support liver regeneration and reduce the risk of liver failure after surgery. Tranexamic acid is a medication that prevents the breakdown of blood clots. It is widely used to manage or prevent excessive bleeding in trauma, heavy menstrual periods, childbirth, and dental or surgical procedures.

"The possibility that a widely available, low-cost medication could substantially reduce this risk is exciting because it has the potential to improve outcomes for patients undergoing surgery for liver cancer and other serious liver diseases," says Patrick Starlinger, M.D., Ph.D., a hepatobiliary and pancreas surgeon at Mayo Clinic in Rochester and co-senior author of the study.

When part of the liver is removed to treat cancer or other conditions, the remaining tissue must regenerate to restore normal organ function. In some patients, that regeneration does not happen after surgery, leading to liver failure.

Researchers first found in pre-clinical models that temporarily reducing plasminogen, a protein involved in the fibrinolytic system, enhanced liver regeneration after resection. They then analyzed data from the HeLiX trial, a large international clinical study in which patients undergoing liver resection received either tranexamic acid or a placebo. The protective effect of tranexamic acid was strongest among patients with impaired liver function before surgery, a group at particularly high risk for post-hepatectomy liver failure.

The findings also challenge a longstanding assumption about liver regeneration.

"For decades, the field believed plasminogen was necessary for liver regeneration based on pre-clinical models," says Dr. Starlinger. "By using a more precise and reversible approach, we found the opposite effect. Our findings open a new avenue for understanding how the body's clotting and fibrinolytic systems influence liver recovery after surgery."

Researchers say the findings support further studies to determine whether tranexamic acid could become part of a strategy to prevent post-hepatectomy liver failure in patients at highest risk.

"While these findings need to be confirmed in a dedicated clinical trial, they provide a strong rationale for evaluating whether tranexamic acid can help protect patients from one of the most feared complications in liver surgery," says Dr. Starlinger.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic study finds common drug may help prevent life-threatening liver failure after surgery appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Researchers at Mayo Clinic have uncovered a previously hidden step in how the immune system prepares to fight cancer, a discovery that could help scientists develop more effective and longer-lasting cancer immunotherapies.

Published in Nature Communications, the study found that some cancer-fighting immune cells begin preparing for their role much earlier than previously believed — while they are still maturing in the thymus, an organ behind the breastbone that plays a central role in training T cells, particularly early in life.

The findings challenge the long-standing view that CD8-positive T cells — a type of immune cells that finds and destroys cancer cells — can leave the thymus in an inactive state and acquire their cancer-fighting abilities only after encountering threats elsewhere in the body. Instead, the research suggests that the thymus may help prepare these immune cells for rapid responses before they enter circulation.

CD8-positive T cells are among the immune system's primary cancer-fighting cells. The researchers found that PD-1 — a protein that is the target of several widely used cancer immunotherapy drugs — acts as a brake during their development, helping prevent these cells from becoming exhausted too quickly.

"Cancer immunotherapy has transformed treatment for many patients, but those responses don't always last," says Zhiming Mao, Ph.D., a recent graduate of Mayo Clinic Graduate School of Biomedical Sciences and first author on the paper. "We've discovered that the immune system may begin preparing for its fight against cancer much earlier than we realized. That insight could help us design therapies that are both more powerful and more durable."

PD-1 is already the target of several immune checkpoint inhibitor therapies used to treat a wide range of cancers, making the discovery particularly relevant to ongoing efforts to improve those treatments.

The findings may provide insight into why some immune responses against cancer are powerful but short-lived. Researchers say future therapies may need to strike a balance between boosting the immune system's attack on tumors and preserving the long-term function of cancer-fighting cells.

In preclinical models, removing PD-1 helped these immune cells control certain tumors more effectively. But the stronger response came at a cost: the cells became exhausted sooner, limiting their long-term cancer-fighting ability.

"Understanding how these immune cells are programmed at the earliest stages of development gives us a new way to think about improving cancer treatment," says Haidong Dong, M.D., Ph.D., an Iris and Winston Clement Professor of Research at Mayo Clinic and senior author of the study.

The findings come as researchers seek ways to make cancer immunotherapies more effective and longer lasting. While these treatments have transformed care for many patients, they do not work for everyone and can lose effectiveness over time.

The findings were based primarily on laboratory and preclinical model studies, and additional research will be needed to determine how they apply to patients.

For a complete list of authors, disclosures and funding, review the publication.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researchers uncover critical link in the immune response to cancer appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic Platform_Accelerate has selected 20 healthcare technology startups to join its accelerator program. Through an immersive 30-week program with a structured curriculum, companies collaborate with leading experts, receive one-on-one technical mentorship, and work with Mayo Clinic Platform's de-identified clinical data ecosystem to advance the development of their digital health solutions.

"The Accelerate program serves as an engine for digital health breakthroughs, offering technology startups resources and expertise to build solutions for long-term impact," says John Halamka, M.D., Dwight and Dian Diercks President of Mayo Clinic Platform. "The digital health solutions represented in this cohort reflect a broader shift in healthcare from experimenting with artificial intelligence (AI) to deploying AI at scale. These innovations have the potential to help healthcare organizations advance patient care, enhance operational efficiency and unlock new ways of supporting patients and clinicians."

The 20 startups participating in the June cohort are working to address complex healthcare challenges.

• Aquoris Intelligence is developing an AI-powered clinical reasoning platform that helps physicians navigate diagnostic complexity, treatment decisions and longitudinal patient context through clinician-centered decision support.
• Burna AI automates evidence-based adverse event grading and coding across the clinical research continuum, improving data quality, operational efficiency and oncology trial execution.
• Cardiolife delivers AI-enabled electrocardiogram (ECG) and Holter monitor interpretation that supports scalable, clinically validated cardiovascular diagnostics while integrating seamlessly into existing care workflows.
• Caremaze uses AI-driven discharge coordination to identify barriers early, streamline multidisciplinary workflows and help health systems reduce length of stay while improving care team efficiency.
• Dr. Data's APEX platform combines clinical guidelines, imaging, digital twins, and real-world evidence to generate transparent, evidence-grounded cardiovascular treatment recommendations.
• éo-vision AI uncovers clinically meaningful signals hidden within medical imaging to support more informed decision-making across healthcare delivery, payer operations and drug development.
• HealMint integrates multimodal AI, continuous biometric monitoring and clinical-grade devices to enable proactive, predictive care for high-risk patient populations.
• Healthier is building an AI-native clinical reasoning platform that synthesizes complex oncology data into source-grounded insights for patients, clinicians and multidisciplinary care teams.
• Immunara leverages biological foundation models and multimodal data to advance precision immunology and uncover new insights into immune-mediated disease.
• InformAI develops AI-powered oncology solutions that accelerate radiation therapy planning and support more efficient, data-driven cancer care delivery.
• Maverick Medical AI automates clinical documentation, coding and revenue integrity workflows to improve reimbursement accuracy and reduce administrative burden at the point of care.
• MICA AI Medical is advancing breast cancer detection through AI-enhanced mammography analysis designed to improve diagnostic accuracy for patients with dense breast tissue while reducing reliance on supplemental imaging.
• Odesso combines clinical AI and intelligent automation to improve risk adjustment, quality performance and value-based care operations through highly accurate clinical data extraction.
• PeriMind applies AI-driven perioperative decision support and revenue optimization to improve surgical workflow efficiency, patient safety and financial performance.
• Plexis AI provides the governed execution infrastructure that enables health systems to safely operationalize AI agents across clinical and operational workflows.
• PrecXIMed is creating an AI-powered neuro-oncology platform that connects imaging analysis, surgical planning and remote monitoring to support coordinated, data-driven brain tumor care.
• Rette AI uses agentic AI and clinical intelligence to automate complex orthopedic revenue cycle processes while improving documentation accuracy and reducing denials.
• Summit Health Data automates clinical data abstraction and applies advanced analytics to accelerate research, improve operational efficiency, and support innovation in cellular therapy and transplant programs.
• SyncVR Medical scales immersive care through enterprise extended reality (XR) solutions that help health systems improve patient experience, reduce procedural anxiety and enhance clinical efficiency.
• ThinkBio.AI transforms complex biological and clinical data into actionable insights that support drug development, translational research and precision healthcare decision-making.

"The Accelerate team designed a program for visionary startups ready to transform healthcare," says Jamie Sundsbak, director of the Accelerate program. "We now offer multiple ways to participate through a 30-week immersive program or a multiyear engagement pathway."

Since its launch in 2022, the Accelerate program has welcomed more than 120 companies from around the world. To learn more about the program or to apply for an upcoming cohort, visit Mayo Clinic Platform_Accelerate.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

About Mayo Clinic Platform
Mayo Clinic Platform is a strategic initiative of Mayo Clinic that enables collaboration, data-driven innovation and responsible AI development to transform healthcare globally. Mayo Clinic Platform is reimagining healthcare as an ecosystem — one where data, digital solutions and expertise flow seamlessly between innovators and care teams to improve care for patients everywhere. 

Media contact:

• Caroline Auger, Mayo Clinic Communications, newsbureau@mayo.edu

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Study uncovers structure of protein that helps cells communicate, a potential drug target

ROCHESTER, Minn. — After nearly four decades of research, Mayo Clinic scientists have revealed the molecular structures of protein kinase C beta (PKCβ), a key protein linked to cancer and neurological diseases. The findings, published in Nature Communications, provide the first detailed view of how the protein works and how the breast cancer drug endoxifen can target this protein.

PKCs are a family of proteins that help cells communicate. They act as molecular switches that regulate cell growth, survival and behavior. Because they play a role in many diseases like Alzheimer's and cancers like breast, lymphoma and colorectal, scientists have long viewed them as promising drug targets. However, without understanding their structure, designing effective therapies has been difficult.

"For decades, scientists have been trying to understand how these proteins function," says study co-author Matthew Goetz, M.D., a medical oncologist at Mayo Clinic Comprehensive Cancer Center. "These findings create new opportunities to develop more precise therapies for cancer and other diseases."

Solving a 4-decade-long mystery

Since PKC was first discovered in the 1980s, scientists have been unable to determine the structure of full-length human PKC enzymes, limiting efforts to understand how they function and how they might be targeted therapeutically.

Led by senior author Matthew Schellenberg, Ph.D., Mayo Clinic researchers overcame this mystery by producing human PKC enzymes that more closely resemble their natural state than proteins generated using traditional insect cell approaches. Their method revealed the structures of human PKCβ1 and PKCβ2.

"By producing the protein in human cells, we were able to obtain high-quality material that enabled us to finally see how this enzyme is organized and regulated," says Dr. Schellenberg, a molecular biologist at Mayo Clinic. "Now, we can begin investigating how changes in these proteins contribute to disease and how new therapies might selectively influence their activity."

How a breast cancer drug inhibits PKCβ

It has been known for decades that PKCβ becomes activated when it interacts with lipid membranes inside cells, but it was not known how this could happen. Structural studies revealed that when membrane lipids bind to PKC, they act like a molecular lever, shifting the enzyme from a closed, inactive state to an open, membrane-bound active state. These membranes trigger changes in the protein, exposing its active site and switching it on.

The researchers then combined structural biology, biochemistry and cellular studies to understand how endoxifen affects PKCβ. They found that endoxifen inhibits PKCβ through an allosteric mechanism, meaning it changes the protein's behavior without directly competing for its active site. The drug appears to stabilize PKCβ at cellular membranes, triggering changes that ultimately lead to its degradation.

"This mechanism is fundamentally different from previous PKC inhibitors that have been tested over the years," Dr. Goetz says. "That distinction may help explain why endoxifen shows biological effects that earlier compounds did not."

Implications for precision medicine

The findings establish a framework for understanding how different PKC family members function in health and disease. Some PKC isoforms may promote tumor growth while others may suppress it. The PKC family includes 10 related proteins, each with distinct roles. Determining when each protein should be activated or inhibited has remained a major unanswered question.

"This study gives us the tools to ask those questions in a much more sophisticated way," Dr. Schellenberg explains. "We can now investigate how different PKC proteins contribute to cancer and design drugs that target the right protein in the right context."

Mayo Clinic researchers are currently studying endoxifen in premenopausal women with estrogen receptor-positive breast cancer and investigating whether its effects on PKCβ contribute to its anticancer activity. The team is planning future work to expand beyond PKCβ to all 10 members of the PKC family, seeking to understand how each enzyme functions and responds to therapeutic compounds in its own unique way.

"We've opened a new door," says Dr. Goetz. "For the first time, we can see how these proteins are organized, how they function and how they may be targeted with greater precision. That understanding could help guide the next generation of therapies."

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researchers map key protein linked to cancer, neurological diseases appeared first on Mayo Clinic News Network.

At Mayo Clinic, neuroscientists are seeking to understand — and ultimately restore — brain function through advanced computational tools, neuromodulation technologies and multidisciplinary collaboration.

These new efforts are led by Gelareh Zadeh, M.D., Ph.D., a neurosurgeon and scientist. Dr. Zadeh specializes in neuro-oncology and has clinical expertise in treating brain tumors such as gliomas and meningiomas. Her research focuses on the molecular and genomic landscape of these tumors to advance precision medicine and improve targeted therapies.

Dr. Zadeh is the David C. and Flora C. Pratt Distinguished Chief Medical Officer for Mayo Clinic Platform, Department of Neurologic Surgery chair at Mayo Clinic in Rochester and the William J. and Charles H. Mayo Professor I of neurosurgery at Mayo Clinic College of Medicine and Science. She is also one of the leaders of the Bioelectronics Neuromodulation Innovation to Cure (BIONIC) initiative, which aims to advance care for complex neurological conditions by uniting clinical insight with cutting-edge engineering to deliver novel diagnostics and therapies.

In this conversation, Dr. Zadeh reflects on the path that led her to neurosurgery, what inspires her and why she believes the medical field is at a turning point in its ability to diagnose, treat and even prevent neurodegenerative diseases.

Watch: Dr. Gelareh Zadeh explains BIONIC

Journalists: Broadcast-quality sound bites are available in the downloads at the bottom of the posts. Name super/CG: Gelareh Zadeh, M.D., Ph.D./Chair-Neuro Surgery/Mayo Clinic

Q: You've said you didn't start out intending to pursue medicine. What originally interested you, and how did you end up in neurosurgery?

A: I actually always wanted to study mathematics. I loved problem-solving — finding the solution at the end of an equation. I began an actuarial mathematics program, but at one point I had to drop a key course. That pushed me to rethink what I really wanted. Friends suggested I take the MCAT and apply to medical school, so I did.

At first, I didn't enjoy medicine. It felt like memorizing facts rather than solving problems. But then I took neuroanatomy with an incredible teacher — a retired neurosurgeon — who made the logic of the brain come alive for me. I shadowed neurologists but didn't feel the same pull. Then one day the neurosurgeons invited me to observe in the operating room. The very first case changed everything. As soon as I saw the brain — its surface, its vessels, its beauty — I knew. This was what I wanted to do.

Interestingly, that neuroanatomy instructor, Dwight Parkinson, had been the first neurosurgeon in Canada and trained at Mayo Clinic. So, in a way, being here now feels like coming full circle.

Q: What about the brain fascinated you so deeply?

A: Its logic. The connectivity of the brain — how different parts work together so I can see you, speak to you, feel an emotion, react — is extraordinarily elegant. Even now, when we stimulate the brain during surgery, I'm amazed at how finely tuned and individual it is. Each person's wiring is like a fingerprint. We know the general map, but the details are uniquely theirs. That complexity still inspires me every day.

Q: You later pursued a doctorate in molecular biology. How did research become part of your path?

A: When I started neurosurgery, I missed the kind of problem-solving I enjoyed in math. At the time, molecular biology was "the language" you needed to understand if you wanted to advance the field, just like AI is today. So I pursued a Ph.D. in the molecular biology of brain tumors and eventually expanded into genomics and epigenomics.

That work shaped how I think. Can we use the unique molecular signatures of tumors to predict behavior? Can computational tools integrate huge data sets to personalize treatment? That journey led naturally to the ideas behind the BIONIC initiative — that the brain's electrical and physiological signatures could also be measured, analyzed and used to guide personalized care.

Q: You've said neurosciences are still in their "infancy." What are the biggest challenges today?

A: We understand anatomy well, especially thanks to brain banking. But what we don't fully understand is function — what changes in a living brain as it degenerates, adapts or recovers. To repair the brain, we need to understand its electrical and physiological activity, not just its structure.

We also need massive data sets. The way your brain functions when you're speaking to me is different from when you're silently thinking. How do we capture that complexity? How do we create feedback loops that respond to an individual's needs in real time? That requires computational power, advanced algorithms and technologies that can deliver precise stimulation.

Q: What role does Mayo Clinic play in making this possible?

A: What drew me here is that we have bioengineering, bioelectronics, computational science and clinical neurosciences integrated within one department. That is rare. It allows us to design the technologies we need — from neuromodulation devices to wearable sensors — and to combine them with clinical expertise and large-scale data.

Q: What is BIONIC, and how would you explain its purpose to a nonscientist?

A: BIONIC is a multidisciplinary ecosystem aimed at restoring brain function. It brings together bioengineers, data scientists, neurosurgeons, neurologists, neuroscientists and neuropathologists — people who don't traditionally work side-by-side — to solve shared problems.

Think of it as several pillars:

• Discovery and data: Collecting and integrating massive data sets across electroencephalograms, MRI, intraoperative recordings and more.
• Technology development: Creating neuromodulation tools, wearables and cellular therapies.
• Clinical translation: Designing clinical trials and regulatory pathways to bring new therapies to patients.
• Disease-specific programs: Focusing on epilepsy, stroke, movement disorders, psychiatric illness and others.

Together, these pieces create an environment where innovations can move from concept to real-world impact.

Q: What are your short-term and long-term goals for the BIONIC initiative?

A: In the short term, we aim to make different brain data streams "speak the same language" so they can be analyzed together. We're also developing what I call the new "brain bank," a repository not of postmortem tissue but of live electrophysiological activity.

In five to 10 years, I hope we will have expanded closed-loop neuromodulation for several conditions and made it part of standard care, both at Mayo Clinic and beyond.

Q: What keeps you motivated in such a demanding field?

A: Solving the puzzle. We can replace joints and transplant organs, but we cannot yet restore lost neuronal function. Now, for the first time, we have the computational and engineering tools to change that. This is the moment to act and build the next generation of therapies that preserve and restore the brain.

The post Inside new efforts at Mayo Clinic to decode and repair the brain using data (VIDEO) appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — One of the most detailed maps to date of meningioma — the most common brain tumor in adults — reveals how the tumor's surrounding environment helps drive disease behavior and patient outcomes, according to new research from Mayo Clinic.

The study, published in Nature Genetics and conducted in collaboration with scientists at Princess Margaret Cancer Centre in Toronto, combines several advanced laboratory techniques to examine tumors at an unprecedented level of detail, offering clues to why some meningiomas grow slowly while others recur or become more aggressive. The findings could lead to more precise ways to predict risk and guide treatment decisions.

Growing evidence suggests that traditional grading systems for meningioma do not fully capture the behavior of these complex tumors, prompting the development of molecular classification tools that more accurately predict which tumors are more likely to recur after surgery. These new findings build on recent developments by investigating the signal from individual cells rather than whole tumors, demonstrating that the tumor microenvironment — the mix of immune and support cells surrounding the tumor — plays a critical role in shaping outcomes.

"We're seeing that it's not just the tumor cells themselves but the ecosystem around them that influences how these tumors grow and respond to treatment," says Gelareh Zadeh, M.D., Ph.D., a Mayo Clinic neurosurgeon and senior author of the study.

Understanding tumor behavior

An estimated 30,000 to 40,000 people in the U.S. are diagnosed with meningioma each year. While many tumors are benign, others can recur or become life-threatening, and predicting that risk has remained a major challenge.

In this study, researchers analyzed hundreds of tumor samples using techniques that allow them to study individual cells rather than averaging signals across the entire tumor. Using single-cell sequencing and spatial transcriptomics, the team mapped more than 500,000 individual cells and millions of data points across tumors. This created a high-resolution "atlas" of the genetic footprint of individual cells and how they differ between aggressive and benign tumors, how they change and evolve over space, and how they interact with other cells in their environment.

"Instead of looking at the tumor as a whole, we can now break it down into its individual components and understand what is driving its behavior," says Dr. Zadeh.

The researchers identified multiple distinct states of immune cells, particularly myeloid cells, that behave differently depending on the tumor. Some of these cell states were linked to more aggressive disease, while others were associated with better outcomes.

Implications for patient care

The findings build on earlier work from Mayo Clinic researchers outlining a new era of personalized care for meningioma, where molecular and cellular insights guide clinical decision-making. This latest study adds a critical layer by showing how the tumor microenvironment contributes to that personalization.

Researchers found that certain immune cell programs were strongly linked to how quickly tumors returned after treatment. In some cases, these signals were able to add value to tumor grade and even modern molecular classification systems in their ability to predict patient outcomes, suggesting they could help refine decisions about surgery, radiation or closer follow-up in the future.

The study also showed that these biological signatures may be detectable through noninvasive approaches, such as blood-based biomarkers, raising the possibility of monitoring patients over time without repeated surgery.

"This moves us closer to a future where we can better stratify patients — identifying who needs more aggressive therapy and who may avoid overtreatment," says Dr. Zadeh.

Beyond improving prognostic tools, the research highlights potential therapeutic targets. By identifying how immune cells and tumor cells communicate, the study points to pathways that could be disrupted to slow tumor growth or enhance treatment response.

Next steps include validating the findings in larger, multicenter cohorts and translating these biological insights into clinical tools and prospective trials.

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic
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Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic maps hidden biology of common brain tumors appeared first on Mayo Clinic News Network.