At Mayo Clinic’s Center for Individualized Medicine, scientists are investigating stool samples to uncover new insights into cancer treatment. Often seen as waste, stool may provide valuable information about the microbiome — a complex ecosystem of microorganisms, including bacteria, fungi and viruses in the gut.

Growing evidence shows the microbiome plays a significant role in health, including how the body responds to diseases like cancer and how it influences treatment outcomes. 

A new frontier in cancer research

A key part of the team's research is the Oncobiome Project, an initiative within the center’s Microbiomics Program. The project includes a large collection of stool samples from cancer patients across Mayo Clinic campuses in Minnesota, Arizona and Florida. These samples, collected before patients began treatment, are helping researchers identify microbial patterns that predict how well a patient will respond to treatments, and potentially pave the way for more personalized cancer care strategies.  

What sets the Oncobiome project apart is its strategic design, which bridges research and clinical practice. This approach makes it easier to translate scientific discoveries into personalized treatments for cancer patients. 

"Ultimately, we hope to individualize treatment plans that provide the right drug at the right time based on a person’s unique microbiome and genetics," says Purna Kashyap, M.B.B.S., the Bernard and Edith Waterman Director of the Mayo Clinic Microbiomics Program.   

Decoding microbiome's cancer link through stool analysis

At the heart of the project is the collection and analysis of more than 2,000 stool samples. This extensive biobank allows Dr. Kashyap and his team to examine whether the microbiome composition correlates with specific types of cancer. They also are investigating whether the microbiome can predict the likelihood of event-free survival for patients with cancers such as lymphoma who are undergoing various treatments.  

Additionally, the project explores whether enzymes and metabolites produced by the gut microbiome can offer insights into how patients will respond to cancer immunotherapies and help identify potential adverse reactions. 

"We included a diverse group of patients at various stages of different cancers and undergoing various treatments. This allows us to identify microbial patterns that forecast optimal cancer outcomes, independent of the underlying cancer," Dr. Kashyap says. 

Beyond personalizing cancer care, the team is integrating additional "omics" to gain deeper insights into patients' genetics, environment and immune status. This includes genomics (the study of genes), proteomics (proteins), exposomics (environmental exposures), metabolomics (metabolic processes) and transcriptomics (RNA transcripts). 

Ruben Mars, Ph.D., a research scientist at the Center for Individualized Medicine, is playing a key role in spearheading several studies within the Oncobiome project to understand the impact of microbes on cancer risk, treatment efficacy and the underlying mechanisms of any treatment side effects. 

"Although a diverse and balanced gut microbiome is widely recognized as beneficial for our health, pinpointing specific microbial changes that enhance treatment outcomes remains challenging," Dr. Mars says. "Through the Oncobiome project, we're optimistic about developing innovative methods to manipulate the microbiome and ultimately improve cancer care for patients." 

Connecting the microbiome to health outcomes

This research is part of a broader series of the team's investigations into the microbiome. Their recent published studies focus on the microbiome's role in gut-brain disorders, including how bacteria affect intestinal functions like motility. Other published work examines C. difficile infections, exploring how the bacteria persist in the intestine.

Mayo's microbiome scientists are also studying the impact of the gut microbiome on the progression of rheumatoid arthritis and patients' response to treatment. In another study, the team linked a specific microbe, Porphyromonas somerae, to endometrial cancer, finding its intracellular activity may play a pathogenic role in the disease. 

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Mayo Clinic researchers have developed an innovative testing strategy for mesothelioma that could potentially increase the detection rate of cancer DNA in the blood. This approach focuses on shuffled or swapped sections of DNA in mesothelioma cancer cells, called chromosomal rearrangements.

By detecting these complex DNA patterns, rather than just single-point mutations, the method could lead to earlier diagnoses and new avenues for targeted therapies. 

“We're pushing the frontiers of what's possible in blood-based monitoring," says Aaron Mansfield, M.D., a medical oncologist and lead author of the study at the Center for Individualized Medicine and the Mayo Clinic Comprehensive Cancer Center. "Improving detection rates could offer insights into monitoring patients' responses to therapy and detecting recurrence after surgery." 

Mesothelioma is a rare cancer that develops in the thin membranes that line the chest and abdomen, most commonly caused by inhaling asbestos fibers. These fibers are often found in insulation, vinyl tiles, roofing materials and paint. Despite decades of regulations to limit asbestos exposure, approximately 3,000 people in the U.S. are diagnosed with mesothelioma each year, according to the American Cancer Society. 

Mesothelioma typically exhibits a low number of single-point genetic mutations, making it difficult to detect with traditional blood tests. However, the presence of chromosomal rearrangements — like shuffling words in a sentence — provides a new diagnostic target. This differs from many other cancers that often rely on detecting single-point mutations — tiny changes in the DNA sequence, similar to altering a single letter in a word. 

In the proof-of-concept study, published in the Journal of Thoracic Oncology Clinical and Research Reports, Dr. Mansfield and his team used whole genome sequencing to locate key chromosomal changes in the DNA of cancer cells. Next, they created tiny pieces of DNA, called primers, that they designed in the lab to precisely match and attach to these chromosomal changes. They then searched for these changes in blood. 

This combination of cutting-edge tools allowed the researchers to create personalized tests that detect and track cancer DNA in each patient's blood. 

The findings build on the team's previous mesothelioma research, including a study that identified a genomic signature to predict which patients with mesothelioma could benefit from immunotherapy.  Additionally, Dr. Mansfield’s previous research shows how chromosomal rearrangements have neoantigenic potential, meaning they can help the body make an immune response against cancer cells. 

The team plans to expand this study to include more patients and further refine the testing method. 

Review the study for a complete list of authors, disclosures and funding. 

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In his 18 months of life, Oliver Bates, with his soft red hair and big blue eyes, left an enduring legacy at Mayo Clinic. Oliver is remembered for his infectious smile and the love and resilience he radiated to all who knew him, even from the intensive care unit. Born with a rare and incurable genetic epilepsy disorder, he inspired a pioneering program designed to expedite genomic-related diagnoses and enhance definitive patient care.  

"Oliver's life was a brief gift, but he left a mark deeper than his time with us," says his mother, Justine Bates, sitting in the comforting glow of purple lights in honor of her baby boy. Those lights, adorning the windows and a memory tree in her Minnesota home, symbolize epilepsy awareness. Close to her heart, Justine has a tattoo of Oliver's small handprint. 

Oliver's father, Casey Bates, will always remember the quiet evenings spent holding his son after work. He proudly displays his own tattoo that reads "Seize the day," a subtle nod to his son's seizure condition and a reminder to cherish every day.  

"He loved to laugh, and he had the best facial expressions. He was my snuggle bug," Casey says. 

Oliver’s diagnostic journey

Oliver's health journey began when he was just five weeks old, when his first seizure led his parents to rush him to a local emergency room. The complexity of his case and the initial hospital's difficulty in diagnosing him led them to transfer Oliver to Mayo Clinic for specialized care. At Mayo, Oliver underwent a comprehensive series of tests, including exome sequencing, which specifically examines 20,000 protein-coding genes where many diseases originate. Although this sequencing technique can provide crucial insights into rare conditions, it can require time for detailed analysis and interpretation of the results. 

While Oliver's initial tests did not reveal the cause of his ongoing seizures, the exome sequencing, which took nearly a month to process, finally helped his care team diagnose Oliver's condition: a rare form of epilepsy known as WWOX-related epileptic encephalopathy (WOREE syndrome). Although the diagnosis helped his care team guide Oliver's care, the condition currently has no cure. He passed away on March 10, 2022, surrounded by his loved ones.  

A new era in genomics

Rare diseases affect 300 million people worldwide, yet only about 25 percent of patients ever receive a diagnosis, and often that diagnosis has no available treatments. Recent advancements in genomic technologies are beginning to offer a glimmer of hope. Clinicians are using these cutting-edge tools, which leverage artificial intelligence (AI) to scour volumes of data, to transform diagnostics and make it possible to identify and understand rare diseases more quickly and accurately than ever before. This is opening avenues for the development of more treatments. 

Oliver inspires genomic advances

Witnessing firsthand the critical need for such advancements, Whitney Thompson, M.D., a key member of Oliver's care team, felt compelled to act, moved by Oliver's family's wait for a diagnosis. With support from the Department of Pediatric and Adolescent Medicine and the Center for Individualized Medicine, she launched an ultra-rapid whole genome sequencing program in Mayo Clinic's neonatal intensive care unit (NICU).  

In this pioneering program, which is a collaboration with Rady Children's Institute for Genomic Medicine, clinicians use new sophisticated technology and AI to sequence a patient's 3 billion DNA base pairs in approximately 48 hours. This comprehensive analysis can identify even the most subtle genetic variants, though it may not always lead to a diagnosis. 

"Rapid diagnoses can lead to lifesaving treatments in some cases, and while not every rare disease has a treatment, every diagnosis brings crucial information that can guide medical decisions and help families anticipate what’s next," says Dr. Thompson, who is completing her fellowship training in Neonatal Medicine, Clinical Genomics and Bioethics as part of the Clinician Investigator Training Program at Mayo Clinic.  

Under this program, through the Mayo Clinic Department of Clinical Genomics with Brendan Lanpher, M.D., as practice chair, infants and children admitted to the Mayo Clinic's Eugenio Litta Children's Hospital in Minnesota undergo ultra-rapid whole genome sequencing if they meet specific criteria. 

The program, launched at Mayo in June 2022, has since been expanded to some adults who exhibit symptoms suggestive of genetic disease, enabling them to receive the same rapid, comprehensive DNA analysis. To date, more than 300 infants, children and adults have been offered whole genome sequencing.  

Dr. Lanpher hopes the program will open the door to more patients having access to comprehensive genetic testing. 

"This is the future of medicine," Dr. Lanpher says. "I believe there are many patients with unrecognized or undiagnosed genetic diseases, and by finding and testing these patients early in the course of symptoms, we'll have the best chance at making a difference, finding a treatment and avoiding a diagnostic odyssey." 

Introducing BabyFORce

Achieving a precision diagnosis is just the first step of a broader goal. Dr. Thompson and her team also have their sights set on rapid individualized therapeutics. She is collaborating with Laura Lambert, Ph.D., director of the Mayo Clinic Functional Omics Resource (FORce), along with Eric Klee, Ph.D., the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation at the Center for Individualized Medicine and Filippo Pinto e Vairo, M.D., Ph.D., director of the center's Program for Rare and Undiagnosed Diseases.  

Together, they have initiated a first-of-its-kind program called BabyFORce, which uses AI to help clinicians identify individualized therapeutics for some of the smallest and sickest patients with genetic diseases in the neonatal intensive care unit. 

"We’re tapping into an advanced AI platform that leverages a 'logic programming' approach, applying set rules to combine and analyze various biomedical data sources," says Dr. Lambert. "This could enable researchers to identify potential drug repurposing opportunities, generate hypotheses and uncover novel insights into disease mechanisms." 

She says the approach could also reduce the time and cost associated with developing new therapies and provide hope for patients with limited treatment options. 

Oliver's impact on pediatric tele-hospice

Oliver's impact extends beyond medical advancements. As his care unfolded during the challenging times of COVID-19, he also inspired Mayo's pediatric palliative care team to start a tele-hospice program. This ensured that children in hospice care could continue to receive compassionate support remotely. 

"All of the providers who cared for Oliver learned so much from him and his family, including how helpful it was to have real-time video assessment of patients with challenging pain and symptoms during in-home hospice visits by nurses," says Christopher Collura, M.D., the Medical Director of Pediatric Palliative Care (ComPASS) at Mayo. "This inspired our team to formalize a tele-hospice program in order to streamline assessments by pediatric palliative medicine physicians for children enrolled with Mayo Clinic Hospice." 

Honoring Oliver and welcoming his baby sister

Throughout Oliver's life and even in his final hours, Dr. Thompson and her team formed a tight, supportive relationship with Oliver and his family, providing comfort and care when it was most needed.  

"Dr. Thompson was really there for us during the hardest time of our lives. And she has continued to support us after Oliver's death," Justine says. "Every year she joins us to honor his memory at our balloon release on Oliver's birthday." 

The Bates family also reached out to Dr. Thompson for guidance on the potential for having another child.   

WOREE syndrome, the genetic condition that affected Oliver, is a recessive disorder. That means both parents carry a copy of the mutated gene but usually show no symptoms. Each pregnancy has a 25% chance of the child inheriting two defective genes — one from each parent — which leads to the disease. Using these genetic insights, Dr. Thompson helped guide the Bates family to the subspecialists who helped them choose a plan that would increase the likelihood of a healthy pregnancy unaffected by the same genetic condition that Oliver had.  

In May, Oliver's legacy was further celebrated with the birth of his baby sister. Justine and Casey named her Whitney, in tribute to Dr. Thompson, reflecting their deep gratitude for the care and dedication Dr. Thompson gave to Oliver and their family.  

"I am deeply touched by this gesture," Dr. Thompson says. "Oliver's story shows us that new beginnings can coexist with cherished memories to help provide healing and comfort." 

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Inside every person are nearly 3 billion DNA base pairs, trillions of cells and microbes, thousands of genes and hundreds of thousands of proteins and other key molecules — a vast collection of data holding clues to health and disease.

At Mayo Clinic's Center for Individualized Medicine, a digital transformation is equipping clinicians with tools to analyze this data and unlock critical insights for patient care. This advancement has the potential to enhance diagnoses and treatments and improve overall patient outcomes.

This shift is expanding the focus beyond traditional measures like blood pressure and cholesterol. Clinicians and scientists are now exploring genetics (genomics) to understand DNA; proteins (proteomics) that drive cellular functions; chemical changes (metabolomics) that reveal how the body responds to diet and environment, along with other biological characteristics. Together, these details provide a fuller picture of a person’s health.  

Each patient’s dataset is massive, containing layers of information that reveal how the body functions at a deeper level. When analyzed collectively, these elements help experts identify patterns and gain new insights into health and disease.  

But gathering this data is only the beginning. As these datasets grow larger and more complex, Mayo's experts are developing and leveraging digital tools to transform raw data into actionable insights.  

Digital Omics powers precision medicine

Leading these efforts is Mayo Clinic's Digital Omics pillar team, co-directed by Eric Klee, Ph.D., the center's Everett J. and Jane M. Hauck Midwest Associate Director, Research and Innovation.  "Omics" refers to the characterization and counting of different biological components — such as genomics, proteomics and metabolomics — and how they are interconnected to influence health.  

"We're giving clinicians the tools they need to connect the dots and make the right decisions for patients," Dr. Klee says.  

One of their key innovations is the Omics Data Platform, a digital library housed in the Mayo Clinic Cloud, which safely stores and organizes the omics data so clinicians and researchers can quickly access this valuable resource. It has reduced many of the barriers to access and created a fast and reliable method for omics data exploration. With tools like the Omics Data Explorer, clinicians can investigate genetic data and quickly identify new insights into the nature of disease. This can potentially lead to faster diagnoses and more targeted treatment options. 

The team also developed a tool called SAVI PI to help doctors and researchers interpret inherited genetic variation and better understand how specific genes may influence a patient's condition. Another Mayo-built platform, MINERVA, links genetic data with clinical information. This allows researchers and clinicians to explore the relationship between genetic variation and patient traits. 

As part of Mayo Clinic's commitment to responsible data stewardship, leaders are working to form an omics data subcommittee to oversee how genomic data is managed and used. The subcommittee will establish clear guidelines so all stakeholders understand their responsibilities for data access and usage. This framework will enhance collaboration, protect patient privacy and ensure ethical data use in research and clinical settings. 

To support clinical data integration, Dr. Klee and his team have launched a "roadshow" to introduce these SAVI PI and MINERVA digital tools to medical and research teams across Mayo Clinic. Through demonstrations and hands-on sessions, they show how the platforms can help them streamline data access and support better patient care. 

Advancing patient care with AI-driven tools 

Meanwhile, Cherisse Marcou, Ph.D., co-director of the center's Digital Omics Program and co-director and vice chair of Information Technology and Bioinformatics in the Clinical Genomics Laboratory, is focused on bringing these advancements directly into patient care. Her team has created an artificial intelligence-driven tool that helps specialists simplify genomic test selection and accelerate genomic data analysis and interpretation.  

Known as the Genetic Optimization and Appropriateness of Testing Tool, or GOATT, this innovation is used by laboratory experts to automate the summarization of important and relevant patient information across the electronic medical record into a concise format. Access to this comprehensive patient clinical summary helps ensure that the right test is ordered for the right patient at the right time. Ultimately, it enables more complete and personalized analysis and interpretation of complex genomic results. 

Dr. Marcou also collaborates closely with clinicians and laboratorians to integrate complex genomic data into Mayo Clinic's electronic health records. 

"Embedding genomic data into the patient's chart in a way that is easy to locate and access — right there, when and where it is needed — will assist doctors in making important decisions and advance the future of genomically informed medicine" she says. "For patients waiting for answers, this access could potentially mean less time spent in uncertainty and quicker guidance on treatment and management options." 

Dr. Klee notes that making these innovations part of routine care is a long-term goal. 

"We hope to make this the standard of care," Dr. Klee says. "We're building a future where precision medicine is no longer the exception but the expectation. We're giving providers and researchers the tools to make the right decisions, and quickly explore new ideas.” 

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Mayo Clinic has been designated a Tier 1 Center of Excellence for Telomere Biology Disorders by Team Telomere, an international organization devoted to improving the lives of those affected by these complex conditions. This recognition reinforces Mayo Clinic's commitment to enhance diagnostic precision, advance patient care and develop groundbreaking treatments. 

Telomere biology disorders, also known as short telomere syndromes or disorders, are rare diseases due to genetic mutations that accelerate shortening of telomeres, which are protective caps at the ends of chromosomes. People with these disorders often face multiple diseases such as pulmonary fibrosis, bone marrow failure, osteoporosis, various cancers and liver fibrosis. Some people experience early signs of aging, like graying hair or fragile nails. 

"Since its launch in 2016 by Mayo Clinic's Center for Individualized Medicine, the Telomere Biology Disorders clinic has rapidly developed into a leading program, now seeing 3-5 new cases each month and serving more than 126 families across its Minnesota and Arizona locations," says Mrinal Patnaik, M.B.B.S., a hematologist and director of the program. "The clinic leverages expertise from hematologists, oncologists, pulmonologists, gastroenterologists, dermatologists, liver specialists, pharmacists, molecular biologists, genetic counselors and more." 

The clinic offers a wide range of diagnostic and treatment options for patients, including: 

• Blood tests (including CBC and liver function tests) 

• Measurement of telomere length 

• Bone marrow studies  

• Lung function testing  

• Advanced imaging techniques such as CT, MRI, MRE and ultrasound 

• Contrast echocardiography and endoscopy 

• Head and neck and anogenital cancer screening 

• Hematopoietic cell transplantation 

• Lung and liver transplantation 

• DEXA scan for bone density 

• Genetic counseling and family screening  

The Tier 1 designation is part of a newly established tier system by Team Telomere that recognizes organizations demonstrating excellence in several key areas, including coordinated and comprehensive care, advocacy and collaborative research efforts.  

Mayo Clinic's status as a Tier 1 center further enhances its leading role in shaping the future of Telomere Biology Disorders management and treatment. 

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Mayo Clinic's 2024 Individualizing Medicine Conference showcased the latest advancements in precision medicine — from artificial intelligence (AI) tools that help specialists detect cancer during surgery to innovative genomic techniques that experts use to map disease risks. But it was the emerging field of "omics" technologies that took center stage. These pioneering sciences — such as decoding our genes (genomics), uncovering environmental exposures (exposomics) and analyzing the microbes that inhabit our bodies (microbiomics) — are transforming healthcare in unprecedented ways. 

Held in September in Rochester, Minnesota, the annual conference, hosted by Mayo Clinic's Center for Individualized Medicine and moderated by Cathy Wurzer, host of "Morning Edition" for Minnesota Public Radio, brought together world-leading scientists and clinicians in precision medicine. Their shared vision: to translate these complex discoveries into personalized care that reduces health disparities and improves outcomes for every patient. 

Setting the stage for change

Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for Mayo Clinic's Center for Individualized Medicine, kicked off the conference with a compelling analogy comparing the rise of omics technologies to a turning point in tennis. He explained that when modern tennis rackets made of carbon fiber and graphite were introduced, players shifted away from net play, relying instead on power and strategy from the back of the court. This change completely reshaped how the game was played. Speaking to an audience that included professionals from healthcare, research and policy, he emphasized that omics technologies, similarly, are revolutionizing how we understand and treat diseases. "Omics will change the practice of medicine," he said. 

Uncovering the health impacts of chemical pollution 

Keynote speaker Philip Landrigan, M.D., director of the Program for Global Public Health and the Global Observatory on Planetary Health at Boston College, highlighted the urgent need to address the health impacts of chemical pollution. "Genetics loads the gun, and the environment pulls the trigger," he said, quoting the famous phrase by Dr. Eric J. Topol, a prominent cardiologist and geneticist. Dr. Landrigan stressed the role of environmental exposures in driving the rise of diseases like childhood cancer, asthma and neurodevelopmental disorders. He also pointed to an alarming trend: since the 1950s, the use of industrial chemicals and plastics have increased exponentially, yet 80% have never been tested for safety. "The only safe level of exposure is zero for many toxic chemicals, especially when it comes to children," he said. He urged the audience not to lose hope and called for health policy advocacy to build a cleaner environment. As an example, he highlighted how healthcare professionals helped remove lead from gasoline through the 1970 establishment of the Environmental Protection Agency. 

Empowering patient-led research

Tania Simoncelli, vice president of Science and Society at the Chan Zuckerberg Initiative, delivered a keynote presentation that underscored the benefits of patient-led research for rare diseases. Simoncelli highlighted the Chan Zuckerberg Initiative's Rare as One project, which empowers patient communities to lead research initiatives, create data registries and drive clinical trials. Simoncelli said, by giving patients a seat at the table, research becomes more dynamic and effective. "Patients are the most important stakeholders, and when empowered, they are powerful forces for change," Simoncelli said. 

Erica Barnes, co-founder of Chloe's Fight Rare Disease Foundation, shared her perspective as a parent advocate. Barnes, whose daughter Chloe was diagnosed with a rare neurodegenerative disorder, discussed the challenges families face when caring for someone with a rare disease. Her presentation emphasized the critical role of patient voices in shaping research priorities and highlighted the need for stronger partnerships between families, researchers and clinicians. "Patients and families bring unique insights that can change the course of research," Barnes said. 

Addressing health disparities and cancer care

Melissa Davis, Ph.D., a researcher at Weill Cornell Medicine, addressed persistent cancer health disparities in marginalized populations. Her research focuses on how genetic ancestry, environmental exposures and social factors combine to drive higher cancer rates and poorer outcomes in African and African American communities. "Understanding how people live, where they are and what they're exposed to can change how we see disease and treat it," she said, urging a shift beyond traditional race-based health research. She highlighted the importance of an ancestry-informed approach to determine risk for breast cancer and guide personalized and effective treatment plans. 

Bridging gaps in genetic risk scores

Iftikhar Kullo, M.D., a Mayo Clinic cardiologist, discussed the use of polygenic risk scores to predict cardiovascular disease, particularly in early-onset cases. He noted that these scores are less accurate for non-European populations due to gaps in genetic data and called for more diverse studies to improve their effectiveness. "We must bridge the gap to ensure that genetic insights benefit everyone, not just a few," he said. Dr. Kullo also shared data showing that patients aware of their genetic risk had lower LDL cholesterol — a type of "bad" cholesterol that can lead to artery blockages — and fewer cardiac events. But he emphasized the need to consider both genetic and environmental factors for accurate risk prediction. 

Imagining AI’s role in the operating room 

Stephen Boppart, M.D., Ph.D., a researcher at the University of Illinois – Urbana Champaign, presented a groundbreaking approach to real-time cancer diagnoses during surgery. His work with AI-powered optical imaging enables surgeons to differentiate between healthy and cancerous tissues on the spot, reducing the need for repeat surgeries. This innovation, which blends real-time feedback with advanced AI, has the potential to significantly improve surgical outcomes. "Imagine a world where AI helps clinicians provide a diagnosis within seconds during surgery," Dr. Boppart said, offering a glimpse into a future where precision medicine meets cutting-edge technology in real time. 

Understanding the microbiome to catch cancers early 

Marina Walther-Antonio, Ph.D., a Mayo Clinic microbiome researcher, shared new insights into the role of the microbiome in early cancer detection and prevention. Her team's work has identified specific microbiome signatures that could serve as biomarkers for early detection of gynecologic cancers, such as endometrial and ovarian cancers. "The microbiome is like an early warning system," Dr. Walther-Antonio explained. "Understanding these microbial communities could help us catch cancers before they develop." 

Rapidly evolving landscape of precision genomics 

Cherisse Marcou, Ph.D., a researcher at Mayo Clinic, shared a new approach to automating and standardizing genomic workflows using advanced AI tools that help clinicians interpret complex genetic data faster and more accurately. "The future of genomics isn’t just about more data, it's about smarter data and turning complex information into clear, actionable insights for clinicians," Dr. Marcou said. She pointed out that these actionable insights can enable quicker answers for patients. 

Stephen Murphy, Ph.D., interim director of the Mayo Clinic Genome Analysis Core, spoke on the rapidly evolving landscape of genomic sequencing technologies. He shared how these advancements are transforming both research and clinical practice in precision medicine. Dr. Murphy emphasized the ongoing shift from targeted gene panels to whole genome sequencing, highlighting how newer approaches like multi-omics, spatial genomics and single-cell technologies are reshaping patient care by offering a deeper and more comprehensive understanding of disease. "The future of genomics isn't just about generating more data—it's about generating the right data and making it actionable for each patient," he said. 

Transforming healthcare in a personalized, data-driven future

The overarching message of Mayo Clinic's 2024 Individualizing Medicine Conference was clear: the future of healthcare will be deeply personalized and data-driven, but this future must reach every patient, everywhere and in a timely and equitable manner. 

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Lewy body dementia (LBD) is a progressive neurodegenerative disease that shares traits with both Parkinson's disease and Alzheimer's disease but can be more difficult to diagnose. Symptoms can include hallucinations, movement disorders, cognitive issues, sleep problems and depression.

To better understand how the disease develops, Mayo Clinic scientists created mini brain models in a dish that closely match key features seen in the brains of patients with Lewy body dementia. Mini brains, also known as brain organoids, are lab-grown clusters of cells that mimic the human brain structure. The team also identified four potential drug compounds that may offer promising approaches to treating the disease. Their findings are published in Science Advances.

There is no cure for LBD, and scientists say there are few accurate preclinical models available to study it. A hallmark of the disease is a protein called alpha-synuclein, which is encoded by the SNCA gene. This protein is found in nerve cells of the brain and can build up into masses called Lewy bodies, which may contribute to symptoms of dementia.

To better understand the pathology of the disease, a Mayo Clinic research team led by neuroscientist and senior author Na Zhao, M.D., Ph.D., developed preclinical mini-brain models using stem cells from LBD patients who had extra copies of the SNCA gene, which may have caused their condition. The patients donated their skin cells upon diagnosis while they were still alive. Scientists then converted the skin cells to stem cells and used them for research.

Using advanced genomic techniques such as single-cell RNA sequencing, which examines genetic material in individual cells, the researchers showed that their mini-brain models mirrored changes seen in the human brains of LBD patients who had donated their brains to the Mayo Clinic Brain Bank, making the models valuable tools for studying how the disease develops.

The researchers used their novel model system to screen nearly 1,300 Food and Drug Administration-approved drugs, identifying four candidates that may help prevent the buildup of alpha-synuclein in neurons.

"This study suggests that these mini-brain models can effectively mimic disease development, providing a potential platform for testing individualized treatments for patients," says Dr. Zhao. "The four identified drug candidates, which have the potential to inhibit alpha-synuclein and restore the energy production in neurons derived from LBD patients, could be further refined or modified to develop new treatments for LBD and associated dementias in the future."

Researchers say additional studies could introduce additional cell types to better mimic the complexity of the human brain. Researchers could then use these enhanced models to further investigate disease mechanisms, such as exploring how high-risk genes influence the development of LBD.

For a complete list of authors, funding and disclosures, see the paper.

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CAR-T cell therapy is a treatment that harnesses the power of a person's immune system to combat cancer cells. In this regenerative immunotherapy, a person's T cells, or white blood cells known as lymphocytes that are involved in the immune system response — are collected and genetically modified to produce chimeric antigen receptors or CARs. They are then infused back into the patient's blood stream, where they target and destroy cancer cells. Mayo Clinic researchers are advancing and improving CAR-T cell therapy to expand its capabilities to treat more conditions. Read more about the latest advances in CAR-T at Mayo Clinic. 

CAR-T cell researchers at Mayo Clinic optimistic about future of treating blood cancers 

While many CAR-T cell therapies use a patient's own cells, Mayo Clinic is also exploring the applications of allogeneic, or "off-the-shelf," CAR-T therapies. These are generated by healthy donors or gene-edited sources that have been genetically altered to reduce the possibility of rejection by the patient's immune system. 

"This can provide a faster turnaround time for manufacturing, expand patient access and allow patients to receive CAR-T cell therapy at the time of need," says Yi Lin, M.D., Ph.D., a hematologist and oncologist at Mayo Clinic Comprehensive Cancer Center. 

CAR-T cell therapy is usually offered as a later-stage therapy for various blood cancers, but recent research has shown it may be useful in some blood cancer cases earlier in a patient's treatment plan.

"CAR-T cell therapy in earlier lines of treatment has reported superior outcomes as compared to using it in later lines of therapy," says Rafael Fonseca, M.D., hematologist at Mayo Clinic Comprehensive Cancer Center. 

Unleashing CAR-T cell therapy to destroy solid tumors in thyroid cancer 

Mayo Clinic researchers are working to apply CAR-T cell therapy to solid tumors in thyroid cancer. CAR-T has shown promising results in blood cancers, and new research is focused on using this treatment on more types of malignancies.

"CAR-T cell therapy is unlike other therapeutics," says Saad Kenderian, M.B., Ch.B., a hematologist and cancer researcher. "Other therapies may slow down cancer. CAR-T cell therapy has shown great promise in stopping B-cell lymphomas and leukemias. Some of my patients have gone into complete remission that has lasted for years after just one treatment." 

Could CAR-T cell therapy improve kidney transplants? 

CAR-T cell therapy could provide a revolutionary approach to organ transplantation for "sensitized patients" who are hard to match and susceptible to rejection, Mayo Clinic researchers discovered. 

Their pioneering research focuses on using CAR-T cells derived from the patient's own immune system to prevent rejection of donated organs. Sensitized patients are those who have high levels of antibodies that cause their immune systems to react negatively to potential donor organs. These patients often face extended waiting periods for a transplant. 
 
Research from this proof-of-concept study is published in Kidney International. 
 
"This research is one of the first steps toward applying CAR-T cells in the field of transplantation to try to make more donor organs available for transplant and reduce the wait for patients who need a new kidney," says Tambi Jarmi, M.D., first author on the study and a transplant nephrologist at Mayo Clinic in Florida. 

Mayo Clinic scientists pioneer immunotherapy technique for autoimmune diseases

Mayo Clinic scientists have developed an immunotherapy strategy that potentially lays the groundwork for treating a spectrum of autoimmune diseases.

The new technique, detailed in a preclinical study published in Nature Biomedical Engineering, involves combining chimeric antigen receptors (CARs) with mesenchymal stromal cells (MSCs), which are found in various tissues in the body and are known for calming down the immune system, controlling inflammation and promoting immune tolerance to prevent the body's own tissues from being attacked. 

"The pioneering approach shows potential in targeting inflammatory disease sites more precisely and improving immunosuppression and healing outcomes," says Dr. Kenderian. "We're planning to study interventions that minimize the need for long-term medications for autoimmune diseases." 

Unleashing viruses aimed at killing cancer 

Mayo Clinic cancer researcher Richard Vile, Ph.D., is leading research into genetically engineered viruses aimed at unleashing a two-pronged attack on cancer. One part of this technology, known as an oncolytic virus, is designed to infect, break open and destroy cancer cells while sparing healthy tissue. Dr. Vile's preclinical studies have shown that oncolytic viruses replicated in cancer cells and cascaded to kill other diseased cells. That, in turn, triggered an immune response in which the patient's own T cells, stimulated by the virus, recognized and targeted metastasized tumors for a second wave of cancer destruction.

"Oncolytic viruses are a way to alert the immune system and mobilize it to kill cells infected with cancer," says Dr. Vile. "There's the direct killing of cancer cells with the virus, and then there's the major effect of immune activation. The immune system is incredibly well evolved to recognize infection, clear infection and kill all the cells around it that could be harboring infection." 

Dr. Vile's team is combining oncolytic viruses with CAR-T cell therapy to target solid tumors from liver cancer. This experimental approach of loading CAR-T cells with oncolytic virus is a new way to expand CAR-T cell therapy beyond treatment for blood cancers into treatment for solid tumors. 

Preparing to biomanufacture a new CAR-T cell therapy for B-cell cancers 

Mayo Clinic research has developed a new type of CAR-T cell therapy aimed at killing B-cell blood cancers that have returned and are no longer responding to treatment. This pioneering technology, designed and developed in the lab of Hong Qin, M.D., Ph.D., killed B-cell tumors grown in the laboratory and tumors implanted in mouse models. The preclinical findings are published in Cancer Immunology, Immunotherapy. 

"This study shows our experimental CAR-T cell therapy targets several blood cancers, specifically chronic lymphocytic leukemia," says Dr. Qin. "Currently there are six different CAR-T cell therapies approved for treatment of relapsed blood cancers. While the results are impressive, not everyone responds to this treatment. Our goal is to provide novel cell therapies shaped to each patient's individual need."

Dr Qin's team developed a cell therapy to target a protein known as B-cell activating factor receptor (BAFF-R) found in patients with B-cell cancers, particularly those with chronic lymphocytic leukemia. The BAFF-R protein is linked to tumor growth. The cell therapy under investigation allows the immune system to quash cancer and target tumors that have returned or have resisted available CAR-T cell therapies. 

Using a molecular scissors to improve CAR-T cell therapy 

Mayo Clinic researchers who mined the molecular foundations of cancer have uncovered a new reason CAR-T cell therapy fails in some patients. This discovery has fueled new strategies that incorporate antibodies and gene editing to improve the outcome of this breakthrough treatment.  

"This is a very exciting discovery that offers new hope of overcoming challenges of CAR-T cell therapy that many cancer patients experience," says Dr. Kenderian, a hematologist and senior author on this research, published in Nature Communications. 

"We describe for the first time a mechanism causing the resistance and failure of CAR-T cells, which lies within a protein routinely made by the engineered cells. This research puts us on a new path for improving the longevity of CAR-T cell therapy." 

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Mayo Clinic’s Center for Individualized Medicine will play a key role in groundbreaking research funded by an award from the Advanced Research Projects Agency for Health (ARPA-H), part of the U.S. Department of Health and Human Services. The research will explore how environmental exposures interact with genetics to affect people's responses to medications — a field known as pharmacoexposomics. 

The five-year award, called IndiPHARM, aspires to develop and execute a state-of-the-art high-resolution, precision monitoring system that aims to evaluate how a large group of people varies in response to drugs for metabolic diseases. The prime research site will be Columbia University, with support from Mayo Clinic, Emory University, Harvard University, Brown University and the Jackson Laboratory in Connecticut.  

This collaboration aims to address why medicines for some metabolic diseases, such as obesity, work for some people and not others and will look at the role environmental exposures — such as chemicals, pollution, diet and lifestyle — may play in people's genetic response. 

Mayo Clinic will use its expertise in genomic research, a large exome dataset of more than 100,000 adult patients that includes all protein-coding genes, and comprehensive longitudinal phenotypes from electronic health records to identify unique patient populations and improve understanding of drug responses. Mayo will oversee the enrollment of study participants as well as the collection and processing of biospecimens to ensure the data meets high-quality standards for analysis.  

Importantly, Mayo investigators will interpret the metabolism of the chosen medications based on available exome sequencing testing of 4,000 participants with metabolic disease and how these observations relate to drug side effects and disease outcomes.  

Shared vision to transform medicine 

Mayo's role in the research will be important in uncovering the missing links in personalized medicine. 

"We've dedicated decades to studying the human genome and mapping its every twist and turn to understand health and disease, but it's only half the story," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for Mayo Clinic's Center for Individualized Medicine. "This ARPA-H award propels us into an uncharted frontier of medical science to explore the other half — the environmental exposures that interconnect with our genetics to drive therapeutic outcomes. Our goal is simple yet profound: to redefine medicine by creating truly personalized treatments that reflect the full picture of each person's health." 

The vision of IndiPHARM is inspired in part by shared goals of Dr. Lazaridis and Gary Miller, Ph.D., Vice Dean for Research Strategy and Innovation and Professor of Environmental Health Sciences at Columbia University Mailman School of Public Health.  

“Medications have the potential to reduce suffering, alleviate symptoms, prevent serious events and help people live longer and healthier lives. Unfortunately, there is a gap between what drugs are predicted to do and what they actually do in the real world,” says Dr. Miller, a globally recognized authority on the exposome. “IndiPHARM is marshaling the technology to bridge this gap.” 

For more on this research, read Columbia University’s news release. 

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Pharmacoexposomics is an emerging field of research focused on understanding how environmental exposures influence a person's response to medication. This new "omics" technology lies at the intersection of pharmacology, exposure science and personalized medicine.

Pharmacology is the study of drugs and their effects, while exposomics is the study of the exposures and other variable factors a person encounters over a lifetime, including chemical exposures, pollutants, diet and lifestyle. The combination of the two disciplines—pharmacoexposomics—explores external factors, including non-medical factors called social determinants of health, affecting how drugs work in people.

"It is an enhancement to pharmacogenomics, which only examines how genetic variation affects responses to medicines," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for Mayo Clinic's Center for Individualized Medicine. "Genes and the environment are two sides of the same coin, and together they hold valuable information for optimizing drug therapy."

For example, variation in a gene called CYP2D6 can influence whether a person is a slow or a fast metabolizer of drugs like antidepressants and opioids. Similarly, exposure to high levels of pollutants such as per- and polyfluoroalkyl substances (PFAS) can affect liver function, altering a person's ability to process certain drugs. Even dietary habits like drinking grapefruit juice can block enzymes that metabolize certain drugs, increasing the risk of adverse effects and modifying their therapeutic effect.

"But these factors do not act in isolation," says Dr. Lazaridis. "We are exposed to millions of naturally occurring and man-made substances that could have a positive or negative impact on our biology. Ultimately, we hope to understand how all these environmental exposures interact with our genomic profiles to influence drug responses." 

Dr. Lazaridis and other researchers are using various "omics" technologies to look for unique signatures of environmental exposures in biospecimens such as blood, urine and saliva that could help to guide therapy. For example, they can look for changes in gene expression from air pollution or measure levels of metabolites that result from the metabolism of specific drugs. By considering environmental factors alongside genetic data, pharmacoexposomics seeks to enhance personalized medicine, tailoring treatment for every patient.

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