Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.

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Mon, Feb 17 6:00am · AI system helps individualize treatment people diagnosed with depression

Dr. Athreya sitting on a ledge in front of a window with scientific writing on it, and Rochester, Minnesota, skyline visible through the window.

When searching for an exact diagnosis through a myriad of complex and serious factors spread across millions of data points, it helps to have a powerful magnifying glass — and another expert point of view.

Enter Arjun Athreya, Ph.D., an engineer by trade who has a knack for bringing together data science algorithms and computing technology to predict events relating to potential disasters lurking within mission-critical cybersecurity infrastructure.

Dr. Athreya is the inaugural doctoral graduate of the Mayo Clinic and University of Illinois Alliance for Technology-Based Healthcare Fellowship program. Now, as a new Mayo Clinic faculty and staff member within Molecular Pharmacology and Experimental Therapeutics, the electrical and computer engineer has his sights set on health care.

Dr. Athreya developed a system for Mayo Clinic that uses artificial intelligence approaches ranging from machine learning to probabilistic graphs to better indicate treatment prognoses in people diagnosed with depression — the leading cause of medical disability worldwide. The system works by identifying patterns within patient history and other relevant data to predict which treatment option is best for the patient’s condition.

“In working with physicians, I learned that finding a diagnosis or treatment prognosis for a complex condition using the huge volumes of data generated from each patient can be like searching for a needle in the haystack,” Dr. Athreya says. “I try to create a magnifying glass to narrow the possibilities down and support the physician’s medical expertise.”

How do AI and machine learning fit into health care?

Mathematical formulations of AI methodologies can discover patterns in a patient’s data — such as genome, microbiome and imaging data — that can explain unique characteristics of the specific patient, allowing for the right treatment to be chosen at the right time and right dose to achieve the therapeutic benefit.

“When people hear AI, they usually feel like they’re going to be replaced by machines,” he says. “First, no doctor will be replaced, as I argued in my doctoral dissertation. Instead, I want to show that AI-based tools serve as an interactive companion to the physician, a technological innovation that assists clinicians in their patient care delivery.”

environmental picture of Dr. Bobo

William Bobo, M.D., is one of the physicians who collaborates with Dr. Athreya as part of a research team that is looking to personalize the treatment of major depression. A variety of treatment methods exist, but because of the timeline required to monitor effects — sometimes spanning several years — patients often grow weary of the process.

“Precision is of utmost importance in medicine,” Dr. Bobo says. “We work to give patients a more accurate diagnosis earlier, to spare them the suffering of their symptoms and the frustration they have.”

By combining the two mutually exclusive fields of direct patient care and data analysis, the team is able to answer that need. Dr. Bobo thinks this unique spirit of collaboration at Mayo Clinic is what makes the approach successful.

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This story originally appeared in Mayo Clinic Magazine.

Read a related article.

Fri, Feb 14 9:44am · Filling hearts instead of test tubes

Merrick Ducharme sitting on the carpeted floor in a playroom with a young boy, playing with action figures.

Editor’s note: This story is not about Mayo Clinic research, but rather about a part of a researcher’s life that builds hope in little hearts, and gives him joy.

It’s 10 a.m. on a Thursday, and Merrick Ducharme is up to his elbows (OK, his wrists) in slime. The gooey, gluey mixture is not one Ducharme, a research assistant at Mayo Clinic, concocts in the pulmonary lab where he spends most of his day. Instead, he’s mixing up the medicine at Mayo Clinic Children’s Center, where he volunteers each Thursday morning. “I try to make the kids forget they’re in the hospital,” Ducharme tells us. “I try to make them smile.”

Ducharme prepared for his research position at Carleton College, where he majored in biology. But he prepared for his volunteer position at home, where giving back was part of the Ducharme family game plan. “Our parents taught us about giving,” he says. “They talked a lot about sharing your gifts.” The family even started a charity together — Thanksgiving in a Bag — after noticing that a food shelf where they volunteered was low on supplies around the holiday. After creating a flyer listing items needed for a Thanksgiving meal, they distributed the fliers and encouraged people to fill a bag with the items and donate them to a food shelf. “We handed them out at church, school and to our sports teams,” Ducharme says. More than 10 years after launching, Thanksgiving in a Bag is still going strong. “There have been thousands of pounds of food collected and distributed,” Ducharme says.

After Ducharme told a colleague about Thanksgiving in a Bag, she told him about her experiences as a volunteer in Mayo’s pediatric center. Then she encouraged him to volunteer there, too. It was an easy sell. Not only does Ducharme have a big heart, he tells us he’s a big kid at heart. “I’ve always loved little kids,” he says. “Playing with kids is an easy way to volunteer.”

Two women and Merrick Ducharme, all in columbia blue volunteer jackets, poised to distribute acrylic paints from a cart full of craft materials.
Merrick Ducharme and some fellow volunteers get ready for some messy fun.

While Ducharme isn’t afraid to get his hands dirty (see: slime), he’s aware that his volunteer role is about more than fun and games. It’s about letting kids — and their parents — know they’re not alone, a way to demonstrate care and give hope. “Hope is my favorite thing about medicine, and there are all kinds of ways of giving hope at Mayo,” Ducharme says. “Surgeons give hope through what they do. Volunteers give hope by being positive and optimistic, and helping patients forget why they’re here.”

Ducharme tells us meeting patients and their families has altered his perspective on life. “I’ve met people who are going through otherworldly circumstances,” he says. “I met a teenager who’s had 60 operations. That would be a lot of operations even for someone at the end of a long life, and he’s just a kid. But he was still able to joke and laugh and be positive.” Ducharme says it was “a reminder of how many things we take for granted.”

Volunteering has also altered Ducharme’s thoughts on the future. He left college imagining a career in neurology or psychiatry. Now, he’s leaning toward pediatrics. “The kids have affected me more than I expected,” he tells us. “My heart just feels full when I leave there. I look forward to it every week. I feel like I’m doing what I’m supposed to be doing.”

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This story was originally published on In the Loop, a subscription-based newsletter and blog that gives a unique perspective on happenings at Mayo Clinic.

Tue, Feb 11 6:00am · Clinical Decision Support: Making It Easy to Do the Right Thing

According to the Office of the National Coordinator for Health Information Technology, clinical decision support provides clinicians, staff, patients or other individuals with knowledge and person-specific information, intelligently filtered or presented at appropriate times, to enhance health and health care.

Matthew Warner, M.D.

At Mayo Clinic there are a range of activities surrounding the development, optimization and implementation of clinical decision support tools.

In a new podcast from the Bow Tie Bandit and Mayo Clinic Laboratories, hear from Matthew Warner, M.D., a Mayo Clinic anesthesiologist. In the podcast you will learn what clinical decision support is, as well as some of the successes and pitfalls of implementation.

Dr. Warner will also talk about some of his experiences with clinical decision support, specifically with regards to patient blood management.


Justin Kreuter, M.D.

Clinical Decision Support: Making It Easy to Do the Right Thing is part of a series of podcasts hosted by Justin Kreuter, M.D., (aka the Bowtie Bandit), discussing various topics related to lab medicine.

Mayo Clinic Laboratories is a global reference laboratory that helps health care providers worldwide advance patient care, strengthen their practices, and broaden access to specialized testing.

Through partnerships with clinicians at Mayo Clinic and health care providers around the world, Mayo Clinic Laboratories is able to offer the most sophisticated test catalog in the world. It is because of these daily collaborations that the Labs’ subspecialized laboratories continue to be a critical component to patient care at Mayo Clinic.

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Related Resources:

Fri, Feb 7 6:00am · Toxic Protein, Linked to Alzheimer's and Other Neurodegenerative Diseases, Exposed in New Detail

By Zuckerman Institute Communications Staff

Alzheimer’s disease brain pathology is illustrated using thioflavin-S fluorescent microscopy, which reveals both neurofibrillary tangles (flame-shaped structures) and amyloid plaque pathology (rounded structures). Through the use of the amyloid brain scanning, we are able to visualize amyloid accumulation in the brains of living individuals – visualized with warmer colors. Read about a related discovery at Mayo Clinic.

The protein tau has long been implicated in Alzheimer’s and a host of other debilitating brain diseases. But scientists have struggled to understand exactly how tau converts from its normal, functional form into a misfolded, harmful one. Now, researchers at Columbia University’s Zuckerman Institute and Mayo Clinic in Florida have used cutting-edge technologies to see tau in unprecedented detail. By analyzing brain tissue from patients, this research team has revealed that modifications to the tau protein may influence the different ways it can misfold in a person’s brain cells. These differences are closely linked to the type of neurodegenerative disease that will develop — and how quickly that disease will spread throughout the brain.

The study, published today in Cell, employed two complementary techniques to map the structure of tau and decipher the effects of additional molecules, called post-translational modifications (PTMs), on its surface. These new structural insights could accelerate the fight against neurodegenerative diseases, by helping researchers identify new biomarkers that detect these disorders before symptoms arise and design new drugs that target specific PTMs, preventing the onset of disease before it wreaks havoc on the brain.

“Tau has long been a protein of significant interest due to its prevalence in disease,” said Anthony Fitzpatrick, PhD, a Principal Investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute who led the study. “In today’s publication, we lay out compelling evidence that PTMs play an important structural role in tauopathies, the collection of neurodegenerative diseases characterized by toxic buildup of misfolded tau.”

Collectively, these results suggest that PTMs may not only be serving as markers on the proteins’ surface, but are actually influencing the behavior of tau.

No two tauopathies are exactly alike, continued Dr. Fitzpatrick, who is also a member of Columbia’s Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. Each affects different parts of the brain — even different cell types — which can lead to different symptoms. Alzheimer’s, for example, arises in the hippocampus, and so affects memory. Chronic traumatic encephalopathy, a disorder most often seen in survivors of traumatic brain injury, can lead to problems with movement, memory or emotion, depending on which areas of the brain are affected.

Abnormal tau protein (brown) in a sample of the brain in Alzheimer’s disease. Tau is deposited throughout the gray matter but not in the underlying white matter. The Mayo Clinic brain bank was the source of the tissues used in this research.

Scientists have used traditional imaging techniques to find clues to how tangles of tau, comprised of individual fibers, or filaments, are implicated in these diseases. But painting a complete picture has proven difficult.

“The brains of patients with neurodegenerative diseases are easy to identify: entire sections have been eaten away, replaced by large clumps and tangles of misfolded proteins like tau,” said Tamta Arakhamia, an undergraduate at Columbia’s School of General Studies, a research assistant in the Fitzpatrick lab and the paper’s co-first author. “However, tau filaments are 10,000 times thinner than the width of a human hair, making them extraordinarily difficult to study in detail.”

To address this challenge, Dr. Fitzpatrick recently pioneered the use of cryo-electron microscopy, or cryo-EM, to visualize individual tau filaments from diseased human brain tissue. Cryo-EM is a Nobel Prize-winning technology developed, in part, by researchers at Columbia University. Cryo-EM images samples using a beam of electrons and has proven indispensable for investigations into extremely small biological structures. Using cryo-EM, Dr. Fitzpatrick’s team has reconstructed the structures of tau filaments, providing new insights into how they form, grow, and spread throughout the brain.

For all its ability to provide highly detailed snapshots of proteins, cryo-EM has limits. To overcome these limits, Dr. Fitzpatrick and his team to paired it with a second technology: mass spectrometry.

“Cryo-EM does not provide a complete picture because it cannot fully recognize the microscopic PTMs on tau’s surface,” said Christina Lee, an undergraduate student at Columbia College, a research assistant in the Fitzpatrick lab and the paper’s co-first author. “But mass spectrometry can pinpoint the chemical composition of PTMs on the surface of tau.”

Working with co-corresponding author Leonard Petrucelli, PhD, Ralph B. and Ruth K. Abrams Professor of Neuroscience at Mayo Clinic in Florida, and Nicholas Seyfried, PhD, professor of biochemistry at Emory University School of Medicine, the researchers used cryo-EM and mass spectrometry to analyze the brain tissue from patients diagnosed with two tauopathies: Alzheimer’s disease and corticobasal degeneration, or CBD. CBD is a rare but extremely aggressive tauopathy, affecting only one in every 10,000 people. Unlike Alzheimer’s, which is thought to arise due to a number of factors including tau, CBD is primarily associated with misbehaving tau proteins.

“Studying a primary tauopathy like CBD helps us to figure out how tau becomes toxic to brain cells,” said Dr. Petrucelli. “We hope to extrapolate that knowledge to secondary tauopathies, such as Alzheimer’s disease.”

The scientists’ analysis of brain tissue samples revealed several key insights. Most notably, the researchers found that cross-talk between PTMs on the surface of tau influences the structure of the tau filaments, contributing to differences in tau filaments observed across the various tauopathies — and even variations from patient to patient.

“Collectively, these results suggest that PTMs may not only be serving as markers on the proteins’ surface, but are actually influencing the behavior of tau,” said Dr. Fitzpatrick, who is also an assistant professor of biochemistry and molecular biophysics at Columbia’s Vagelos College of Physicians and Surgeons.

Moving forward, Dr. Fitzpatrick and his team plan to expand this work to other tauopathies. Today’s findings on Alzheimer’s and CBD hold immense promise for the field, particularly in the development of new disease models — such as lab-grown organoids, or mini-brains — that may serve to accurately recapitulate what is actually happening in the brains of patients.

“Our findings will inspire new approaches for developing diagnostic tools and designing drugs, such as targeting PTM vulnerabilities to slow disease progression,” said Dr. Fitzpatrick. “Neurodegenerative diseases are among the most complex and distressing class of illnesses, but through our work and that of our colleagues and collaborators, we are building a roadmap toward successful diagnostics and therapeutics.”

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Editor’s Notes:

Thu, Feb 6 6:00am · Improving the quality of life for the aging population in Rochester and beyond

an elderly or senior man and woman driving in a car with a couple of friends in the back seat, laughing and smiling

By Adolfo Espitia Jr., public affairs intern

Diagnosed with pulmonary hypertension
some years ago, Elizabeth, now 65, was left with a debilitating condition that
prevented her from even light activities. She had to rely on her husband to
take care of their home. Finally, the medications she had taken for 10 years
stopped working, forcing her to undergo a heart-double lung transplant in late 2013.

Post-transplant was a rough experience,
as Elizabeth described it. After being hospitalized numerous times it
eventually left her so weak she had to use a wheelchair. Elizabeth started
cardio-pulmonary rehabilitation for 16 weeks to regain her walking ability. Now
a widow, she no longer lives in her house.

Her Mayo Clinic physician suggested continuing exercise after her rehabilitation finished, referring her to the senior center in Rochester, Minnesota (125 Live, now rebranded as a center for active adults of all ages). With her untiring determination, Elizabeth was finally able to stand with the support of a cane.

In ideal situations, it’s geriatricians
that serve aging adults like Elizabeth. These medical specialists focus on the
needs and conditions that face aging patients.

Geriatrics – an
expanding need with few providers

By 2050, 20% of the U.S. population will
be considered “elderly.” With a rising aging population, the demand for
geriatricians is increasing. The American Geriatrics Society predicts a 45%
increase in demand for geriatricians from 2013-2025.

However, as of 2017, there were only
7,000 certified geriatricians in the U.S. In Minnesota, there were only a total
of 144.

Geriatricians are trained in age-related
illnesses like osteoporosis, heart disease and neurological disorders like
Alzheimer’s and dementia, in contrast to general or family practitioners whose
training is much broader.

To bolster the capabilities of existing geriatricians, the Mayo Clinic Robert and Arlene Kogod Center on Aging conducts innovative research focused on improving the quality of life for seniors. Groundbreaking research marks new hope to alleviate age-related diseases. Meanwhile, community centers like 125 Live provide resources and encourage activity for more fulfillment in life’s final phase.

Lilia Ponton, M.D., a geriatrician at Olmsted Medical Center, just down the road from Mayo Clinic, is among those 144 Minnesota geriatricians. Her concerns involve all the unique challenges on treating elderly patients. For example, older adults experiencing delirium can lose independence, forcing them to rely on a caregiver. It could become dangerous for the patient, or the caregiver, if the caregiver isn’t aware of the older adult’s medical history.

Other illnesses and health conditions
also pose unique health and safety risks for older adults, the most common
being falls.  The U.S. Centers for
Disease Control and Prevention says that falls are the
leading cause of fatal injury among older adults
. Non-fatal
falls cost more than $50 billion dollars each year, and those costs continue to
rise.

Dr. Ponton says that improving quality
of life for older people could decrease falls and hospitalizations, potentially
improving health care costs.

However, there still is a concerning
shortage of geriatric care providers across the nation, she says.

Mayo Clinic hopes to change that, and is launching a plan to inspire a new generation of geriatricians and gerontology researchers.

A new geroscience training program to spark interest in elder care

Robert Pignolo, M.D., Ph.D., is a geriatrician at Mayo Clinic. He agrees that languishing class sizes in geriatric medicine could potentially cause a real problem. That’s why the Mayo Clinic Kogod Center on Aging, in collaboration with the Mayo Clinic Center for Clinical and Translational Science launched a new geroscience training program in mid-2019. (Read more.)

The program focuses on the areas of expertise
needed to conduct clinical trials: standard clinical research, geriatric
medicine, geriatric clinical research and geroscience. Research in this area
could ultimately benefit individuals by finding ways to slow or reverse the
cellular causes of aging as opposed to treating specific age-related diseases.

Currently Mayo Clinic’s geroscience program is advancing current research on cellular senescence. Senescent cells are believed to be the cause of aging-related illnesses like Alzheimer’s and osteoporosis. By removing these senescent cells, the quality of life may be improved for older adults.

Dr. Pignolo says by 2050, 20% of the
U.S. population will be considered elderly, urgently calling for renewed
interest in geroscience.

“Outside of geriatrics it will get
people interested, whatever their field is to look at aging in older patients
in a different way,” Dr. Pignolo says. “Just because someone is very old it
doesn’t mean they’re automatically excluded from possibly getting better.”

Even though the program is still in its
infancy, Dr. Pignolo is optimistic and hopes that new opportunities within the program
will attract geriatricians and non-geriatricians alike.

Healthy aging, from within

Mayo Clinic makes scientific breakthroughs with cellular senescence

As humans age, there is a greater likelihood of being diagnosed with an age-related illness. James Kirkland, M.D., Ph.D., director of the Mayo Clinic Kogod Center on Aging found that senescent cells prevent the creation of new cells, causing a build-up of old, damaged cells.

“The fundamental aging process is the
root cause and contributor of diseases and disabilities that accumulate with
aging,” he says.

Based on Mayo Clinic research from 2015 and 2016 studying mice with osteoporosis, Mayo Clinic partnered with the Wake Forest School of Medicine, Winston-Salem, North Carolina, and the University of Texas Health Sciences Center at San Antonio, to conduct the first human clinical trial, publishing their findings in early 2019.

The study treated patients with
pulmonary fibrosis and sought to determine whether senolytic drugs — agents
that remove senescent cells — could delay fundamental aging processes.

Dr. Kirkland says the study concluded
that the drugs alleviated some physical dysfunction and improved other physical
performances. After additional research, Dr. Kirkland hopes to perform a larger
clinical trial with patients who have several chronic conditions.

For Dr. Kirkland, the goal of the
research is not to extend the lifespan, but to improve one’s health span.

“We want to improve health later in
life, we don’t want to prescribe better wheelchairs or walkers,” Dr. Kirkland
says. “It would be ideal if we had people who were 80 or 90 feel like they were
40.”

One example he cites is cardiovascular
disease. Although fewer individuals are dying from heart attacks, survivors may
not completely recover. This, Dr. Kirkland says, is where senolytic drugs could
improve physical recovery and could also give back a sense of dignity for older
adults who otherwise couldn’t perform daily tasks like standing or getting
dressed.

Meanwhile, on a community level, older adults are beginning to take their quality of life into their own hands. They beg for terms like “senior” and “senile” to be tossed.

The aging population no longer accepts the traditional aging lifestyle.

Which brings us back to Elizabeth, one
of those aging community members.

Beyond graduating from a wheelchair to
standing with a cane, Elizabeth’s devotion to exercise and improving strength paid
off. She was finally able to stand, exercise and swim independently. Her
physicians praise her for her devotion to physical activity.

Community centers like 125 Live have
given older adults like Elizabeth a second chance.

At 125 Live, the mission is to place activity
back in control of the older adult. Sylwia Bujak-Oliver, 125 Live’s executive
director, emphasizes that age should not determine one’s capabilities.

“People are generally going away from
the word ‘senior’ because there’s a conception that the individual is senile,
or needs help,” Bujak says. “You are an independent individual and you have
your own free will. We will modify and adjust to your abilities, but we will
not be telling you that you can’t do something.”

Older adults visit 125 Live for other
resources in addition to physical activity. Part of aging is the loss of
friends and family and declining health. To lessen isolation, Bujak-Oliver says
125 Live offers support groups on topics ranging from grief to neurogenerative
disorders.

One of these groups helped Dan, 71, who
sought companionship and social interaction after his wife passed away in 2012.

Bujak says members regularly approach
her to relay how 125 Live has improved their health and quality of life.

Lucinda, 78, is another example how
activity could benefit older adults.

After being diagnosed in late 2018 with
ovarian cancer, Lucinda’s prognosis was “not good.” Because of her age, many
surgeons would have hesitated, unsure if she would be able to tolerate abdominal
surgery. However, because of Lucinda’s diligence in staying active, her doctors
felt safe to operate. The surgery was successful and now Lucinda continues physical
activity.

“I believe joining this center and participating in activities they have here is what really got me through it (ovarian cancer),” Lucinda says. “They (doctors) keep telling me it really is a miracle that I am as strong as I am and able to do what I do with that terrible phrase, ‘at your age.’

“I’m proud of my age,” she says.

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Wed, Feb 5 6:00am · "I Just Didn't Understand": On a Mission to Cure ALS

By Barbara J. Toman

For Veronique Belzil, Ph.D., the fight against amyotrophic lateral sclerosis (ALS) is personal. In 2000, while working as a psychologist in Canada, she watched her husband’s uncle succumb to the disease. “The progression was so fast and his condition was so sad,” she says. “I just didn’t understand how this could happen.”

That’s a common experience for people who lose loved ones to ALS, a devastating neurodegenerative disease with no cure. But Dr. Belzil’s next step was uncommon: Returning to school to pursue a doctorate in neuroscience, with a focus on ALS. “I decided to take this experience as a mission to find a treatment for this terrible disease,” she says.

Now, as an epigenomics researcher for the Center for Individualized Medicine at Mayo Clinic’s campus in Florida, Dr. Belzil is paving the way for improved diagnosis and treatment of ALS. “We’ve made tremendous progress in terms of understanding the biology behind the disease,” she says. “There is great hope for these patients.”

Often known as Lou Gehrig’s disease, ALS affects nerve cells in the brain and spinal cord, causing loss of muscle control. About 5,000 people in the United States are diagnosed with ALS each year. Diagnosis occurs around age 60, and average survival is three years. Although ALS can be inherited (“familial ALS”), most people with ALS don’t have a family history of the disease (“sporadic ALS”).

“We’ve made tremendous progress in terms of understanding the biology behind the disease. There is great hope for these patients.”

Veronique Belzil, Ph.D.

Finding treatments for ALS requires first understanding how the disease develops so researchers know what to target. About 30 genetic mutations have been identified as playing a role, including a mutation known as C9orf72, which was discovered at Mayo Clinic’s campus in Florida. The most common mutation associated with ALS, the C9orf72 variation explains a large proportion of familial ALS and a small proportion of sporadic cases.

However, in more than 80% of people with ALS, the disease has no known genetic cause. What’s more, people with the same genetic mutation can have very different disease characteristics. “That indicates there must be something else that triggers the disease,” Dr. Belzil says.

The answer may well lie in the epigenome — the factors such as environmental triggers and gene regulators that influence how a gene is expressed. Early in her research career, Dr. Belzil decided to investigate epigenetic changes in people with ALS.

“This was a new direction that wasn’t being explored a lot at the time,” she says. “The epigenome is very dynamic. But if we can understand these dynamics, then therapeutic strategies can be developed to target the regulators of these actions. The goal is to reverse the epigenetic changes that lead to neurodegeneration.”

“The epigenome is very dynamic. But if we can understand these dynamics, then therapeutic strategies can be developed to target the regulators of these actions. The goal is to reverse the epigenetic changes that lead to neurodegeneration.”

Solving the ALS riddle will take time. But Dr. Belzil and her colleagues have already learned a lot. In one recent study, the researchers identified numerous occurrences of an epigenetic mechanism known as DNA methylation in people with ALS compared to people without the disease. That study was the first to find that methylation changes in familial and sporadic ALS are generally distinct, although people within each group shared thousands of these aberrations.

“Our results are particularly important for sporadic ALS cases, as there is currently no known common cause,” Dr. Belzil says. “Aberrant methylation may be key to understanding the disease and developing treatments.”

Other epigenetic changes under investigation include histone modifications and small RNA regulation. All of this work can potentially lead to the discovery of an ALS biomarker — a measurable indicator that the disease is present. Right now, ALS is difficult to diagnose early because it can mimic other neurological diseases.

“Clinically relevant biomarkers would facilitate early diagnosis of ALS and predict prognosis,” Dr. Belzil says.

Biomarkers are also important for clinical trials of new treatments. “There is a lot of variation in how ALS manifests in patients,” Dr. Belzil says. “A biomarker can group patients appropriately to determine if a new therapy is having an effect within that group.”

Outside of the laboratory, Dr. Belzil is active in the ALS Association, a patient advocacy group. Her efforts include speaking to patients and caregivers about ALS as well as participating in sponsored walks and other fundraisers.

“Awareness of ALS has grown, and more researchers are working on it now,” Dr. Belzil says. “It is a devastating disease not only for patients but also for caregivers and family members. Understanding ALS and developing therapies will have a major impact on all people affected by the disease.”

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This story was originally published on the Center for Individualized Medicine blog.

Mon, Feb 3 6:00pm · Merging minds to accelerate research discovery

Mayo Clinic and Arizona State University formed the Mayo Clinic and Arizona State University Alliance for Health Care in 2010 to merge minds and accelerate research discoveries, improve patient care through innovation and transform medical education to enhance health outcomes. Highlights of two of the joint research efforts follow.

Identifying a blood-based biomarker for early-stage Parkinson’s disease

Charles Adler, M.D., Ph.D.

Researchers know that patients with Parkinson’s disease and other neurodegenerative disorders have abnormal accumulations of different proteins in the brain. In Parkinson’s disease this is mainly the protein alpha synuclein. There also may be small soluble aggregates of these proteins that result in a distinct protein variant biomarker profile.

Michael Sierks, Ph.D.

The Mayo-ASU team plans to analyze blood samples from early and advanced Parkinson’s patients to see if the protein patterns change as the disease progresses. There also are plans to study individuals who may be at risk for developing Parkinson’s disease to determine if the protein patterns could predict who will develop the disease. The team hopes to obtain biological samples from individuals who have donated their bodies to science and were found upon autopsy to have indicators that they may have developed Parkinson’s if they had lived longer.

These samples will help researchers identify the precise abnormal form of synuclein that indicates early-stage Parkinson’s disease so physicians potentially can begin testing for it.

Dr. Sierks has had success identifying biomarkers that have been used to diagnose Alzheimer’s disease as early as five to 10 years before an initial diagnosis of mild cognitive impairment. He believes the same is possible for Parkinson’s.

Fighting disease-causing bacteria in wounds

Robin Patel, M.D.

Researchers have identified that a type of clay can kill bacteria, including many drug-resistant pathogens, and diminish populations of bacterial biofilms that make the bacteria relatively resistant to antibiotics. These biofilms appear in two-thirds of infections seen by health care providers.

Lynda Williams, Ph.D.

Under laboratory conditions, one concentration of Oregon blue clay suspension killed bacteria including Escherichia coli and Staphylococcus aureus and strains such as carbapenem-resistant Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA).

These results support efforts to design new antibacterial drugs using natural clays.



Fri, Jan 31 6:00am · How a love for learning inspired an investment in physicians of the future

Jay Alix grew up surrounded by an unlikely team of experts. That, and a supportive community, gave him a push that turned him into a world-class business leader. Now a member of the Mayo Clinic Board of Trustees, he’s sharing his legendary business acumen to help Mayo Clinic educate the next generation of physician-scientists and to transform medicine.

To understand Jay Alix’s desire to give back to education, it’s important to go back to the unlikely time and place where he began his own learning experience — at his family’s Shell service station nestled in Waterbury, Connecticut.

From the time his mother stitched Jay his very own service station uniform at age 4, Jay received business lessons that laid the foundation for everything that would come in his career — and eventually his transformational gift to Mayo Clinic that the organization recognizes by naming the medical school Mayo Clinic Alix School of Medicine.

The Shell service station was more than just pumps — it was a hub of activity harkening back to an earlier time when stations provided full services, from repair to towing, and worked hard to cultivate a regular clientele by solving the customers’ problems.

One of the ways his parents encouraged him to work harder in grammar school was by rewarding Jay with additional hours at the station. He learned all manner of business and life lessons from his father, the mechanics and car dealers, the customers and their families, and more who came through the doors weekly, for years.

At 18, Jay became the youngest person in the Shell dealer training organization to be certified as a Shell dealer. It was a result of what he’d learned: developing expertise, putting customers’ needs first and relying on a team of employees with specialized skills. Jay and his father took pride in Shell’s motto — “Service Is Our Business.”

But one thing Jay wasn’t sure about was what was next in his life. He loved the service station. His vision revolved around a regional network of stations — maybe bigger. He went to the local junior college for an associate degree in marketing and management to further those goals.

“I was happy. I wasn’t sure I wanted to go to a university, but my dad said, ‘Why don’t you try it? You can always come back if it doesn’t work out,’” Jay says. “There were two parts to his advice — first, there were no expectations. Second, I could always come back to what I knew and loved. It was encouragement without expectation.”

Still, that didn’t mean Jay was primed or successful in everything that came next. It was perseverance and unwavering values that drove him to eventually become an innovator so visionary that a whole industry sprang up from his work of solving corporate problems and turning around distressed companies.

An Ideal Model

Jay’s parents and the community of regular customers who watched him grow up encouraged him to broaden his horizon. Jay entered the only school he applied to at the time — the Wharton School of the University of Pennsylvania. He went on to Rutgers University, where he earned an MBA and then passed the CPA exam. At the age of 25, just a few years out of college, he founded his own business, Jay Alix, CPA PC, a corporate turnaround firm.

Success followed. The firm evolved into Jay Alix & Associates, and at 31, he turned around Phoenix Steel Corp., the oldest steel company in the country. Soon more national and international brands came calling — Unisys, National Car Rental, Zenith, DirecTV, Ryder Trucks and countless others. His firm eventually became AlixPartners in 2002, and Jay retired as the largest shareholder in 2006.

While growing his own business over 25 years, Jay always sought out mentorship from entrepreneurs, business leaders and academics. In particular, he took a strong interest in and studied Mayo Clinic and other organizations started by a single person or family that later grew into top-flight businesses in different fields, such as finance, law, health care and more.

“I became fascinated in my continuing business education with Mayo Clinic’s model of care, which had thrived for more than 150 years,” Jay says. “It was impactful for me to see the health care analogies and metaphors as I built the architecture of my ‘corporate health care’ businesses.”

Studying Mayo Clinic and modeling parts of his company after it in the 1980s, Jay became even more interested in Mayo Clinic’s success following his first patient care experience in the 1990s.

“In 1994, I went to Mayo Clinic for my first executive physical. I was so impressed and so taken by it,” Jay says. “Now, I go many times a year, not because of a health issue, but because of the people.”

A Mayo-Minded Focus

Watching Mayo Clinic, and searching for his main philanthropic mission, Jay saw an opportunity to make a significant impact at Mayo through conversations with former President and CEO John Noseworthy, M.D.

Jay’s advising role and gifts grew over many years, supporting the Mayo Clinic Model of Care, which features unhurried exams and focuses on the highest-quality patient care with comprehensive and efficient evaluation, assessment and treatment. But there was another need — addressing the prohibitive costs young people must bear to receive a medical education.

“We need to ensure more people can choose to go to medical school. We need to make a medical education more affordable for people,” Jay says. “We must lower the cost burden to enter the profession so the best and brightest will choose to become doctors.”

To do so, Jay made a transformational gift to Mayo Clinic of $200 million. He also deepened his time commitment to Mayo Clinic to ensure its long-term success by joining the Board of Trustees. In recognition of the gift, Mayo Clinic named its medical school Mayo Clinic Alix School of Medicine and recognizes Jay as a Philanthropic Partner.

“It couldn’t be a more satisfying, gratifying, enriching part of my life,” Jay says.

“Mayo Clinic’s unique approach to medical care, education and research changes the outcome for patients and provides hope. This was the inspiration for my own successful business model, and if I can pay that forward and help Mayo Clinic by using my time, abilities and resources, that’s my way to impact millions of lives as part of the Mayo team.”

Jay Alix

And that’s a big part of what drew him to supporting education — solving a pressing problem and the need for more doctors by providing a large-scale solution to help educate the next generation of physicians.

Mayo Clinic Alix School of Medicine is a top 10-ranked national medical school, currently growing to graduate 100 doctors each year by 2021. About one-third of those graduates go on to join Mayo Clinic’s staff, while the rest use the knowledge received through training at Mayo Clinic to enhance other medical practices.

“The next generation of Mayo Clinic’s leaders is being trained now,” Jay says. “They will perpetuate the Mayo Clinic Model of Care and will fulfill the mission to meet the needs of patients first.”

Impacting Millions, One at a Time

Jay’s philosophy is refreshingly simple.

“I’ve become convinced that the nature and quality of our lives will be determined by the nature and the quality of our relationships,” Jay says. “So, if we form positive, productive relationships with high-quality, high-integrity people, really good human beings, we will likely have a high-quality positive life and we, too, will help them improve the quality of their lives.”

That’s what he sees in the eyes of all the students he meets at Mayo Clinic Alix School of Medicine. Jay mentions that one of his greatest joys and a source of inspiration is to hear the students’ own stories of overcoming adversity, because it reminds him of the vital role education played in his own life.

“One of the lessons I’ve learned — the pursuit of happiness isn’t a job; it isn’t climbing a career ladder,” Jay says. “It’s about being productive, intellectually honest and doing things for the greater good. That gives us a stronger sense of self-esteem and self-worth, and purpose, and that’s where we find real satisfaction and ultimate happiness.”

And, when people of integrity have the time and space to think clearly and logically as well as humanistically about issues at hand, Jay believes that’s when even the biggest problems can be solved.

A System of Success

candid photo of Jay Alix holding notecards and pencil, and animatedly discussing something

For Jay, it starts with a No. 2 pencil and 3-by-5 notecards and a time management system he learned from an early mentor about 40 years ago.

“The cards are my priority-setting and time management system. It helps clear my mind. The idea is, people make a big effort around a to-do list, but you can only do one thing, one task at a time. Most important achievements are made up of big, complex projects and solving major problems. But if you break complex things down to one item at a time on an index card, it focuses all your attention, and in a physical way it can be accomplished or solved quickly.

“Life is lived in the present, from moment to moment, from task to task. The past is gone, the future is not yet here. By being as present as possible, you can listen carefully and become a positive influence for solving problems.”

Opportunity Abounds

Jay’s list of people he admires at Mayo Clinic runs so long that he’s afraid of missing someone, but he acknowledges his friendship with Dr. Noseworthy and Gianrico Farrugia, M.D., Mayo Clinic president and CEO, as well as Mayo Clinic’s internal leadership board and department chairs.

In appreciation, he wanted to do something beyond his $200 million gift that would be innovative for Mayo Clinic’s future leaders. He worked with Dr. Noseworthy, who was president and CEO from 2009 through 2018 — a period of unprecedented growth as well as challenges — to create an endowment.

“One of the things I witnessed in the clinic from leadership is that there are always more great ideas than there are funds for,” Jay says. “By creating an endowed position supporting the CEO this year, it’ll produce a source of funding so President and CEO Gianrico Farrugia, M.D., and all future CEOs can bring about bright ideas that will advance Mayo Clinic as a global institution.”

No matter what the future holds, Jay believes Mayo Clinic’s mission will remain paramount because of the personal commitment and individual dedication of Mayo Clinic’s staff.

“It’s a joy to collaboratively work with Mayo people. They are dedicated, smart, hardworking people; they have personal missions to help heal and cure the world,” Jay says. “When I see people at Mayo Clinic working together, collaborating to discover a solution to a patient’s problem because they’re sick or hurting and they’re healed and they feel better, that’s very inspiring.”

And it’s one thing that won’t ever change.

“Mayo Clinic keeps its eye on what makes it special — patient encounters. Each individual episode of care makes Mayo Clinic the exceptional place it is every day,” Jay says.

“The world is changing rapidly, and that won’t stop. Mayo Clinic will continue to evolve and lead the charge of the change in health care. Mayo Clinic will continue to influence the practice of medicine through doctors, scientists, researchers, students, staff.”

Jay Alix

A Joyful Time

There are opportunities for milestones ahead in Jay’s own life, including several he’s looking forward to with his partner, Una Jackman. He’s taking it all in stride, one day at a time.

“It brings me joy to think that I’ll be a grandparent,” he says, smiling.

Is one of Jay’s or Una’s six children between them expecting a baby?

“Well, not yet,” he chuckles. “But our kids will definitely be reading this.”

Still smiling, he thinks about their impact in his own life.

“Watching them as young adults as they take on life’s challenges makes me so proud. It’s joyful to see their lives continue to unfold as they grow and prosper.”

And with that, Jay reflects on all of his experiences, and how bright the future is to come.

“It’s meaningful and purposeful to see my own life in context, with the abilities and opportunities I was given, and to be able to fulfill the legacy of sacrifices my parents and grandparents made, by making a gift to help students work for the greatest good and help Mayo Clinic,” Jay says.

“And now I see it continuing far into my family’s future because in the end, it’s about how we help each other, and how we help humankind — in all ways.”

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This story was originally published in Mayo Clinic Magazine.

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