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Mon, Feb 4 6:00am · Meet Chuanhe Yu, Ph.D.: searching for the genetic switches linked to disease

Chuanhe Yu, Ph.D.

Chuanhe Yu, Ph.D. has always had an interest in genetics – the thousands of genes that make each of us unique. His research focuses on the growing field of epigenetics, which aims to better understand how environmental and lifestyle factors cause chain reactions, flipping the switch on genes and the  instructions they provide to guide our body’s functions. It’s these changes that could be linked to the development of disease.

For Dr. Yu, the most exciting part of his work is the possibility that the mechanisms he observes could be reversed, and may lead to new therapies to treat diseases like cancer.

“We can’t change our genetic sequence, but we can potentially reverse epigenetic code that leads to disease. First, we must overcome the challenge that researchers have faced for years. We need to observe the biological and genetic process taking place as cells divide and grow in the body. We’ve recently developed a tool that provides a window into these processes, and we’re just beginning to analyze the significance of what we’ve uncovered,” says Dr. Yu.

Originally from China, Dr. Yu earned his Ph.D. in genetics from Iowa State University. Drawn by Mayo Clinic’s reputation for excellence in clinical care and research, he joined the Center for Individualized Medicine Epigenomics Program research team in 2012.

How an electric piano can help explain the importance of epigenetics

Piano keyboard with headphones for music

For a pianist, an electronic keyboard offers many different ways to play the same musical notes, without changing the keys. With the touch a button, players can shift the tempo of the music and the sound of each note, even combining effects to create a new interpretation of the original song.

Consider now that the genes in our bodies are like the keys on the piano. They can’t be changed, but how our genes guide our body’s functions can.

Our epigenome is similar to the different effects a pianist can use on the keyboard. It is made up of a multitude of chemical compounds and proteins that can attach to our DNA, changing how the genes (like the piano keys) perform in our bodies.

Just as a pianist can flip a switch on the keyboard, changes in our epigenome can switch on or off genes, leading to uncontrolled growth, a hallmark of cancer, or to a failure in our immune system’s ability to destroy tumors or other diseases.

As Dr. Yu explains, some of the changes in the epigenome are linked to our environments and our lifestyle choices, such as what we eat and whether we smoke or drink alcohol.

“Human cells can respond and adapt to environmental changes through different mechanisms, including epigenome response. But there are many factors that can interfere with these mechanisms. For example, sustained exposure to tobacco can cause epigenetic alterations that turn a normal cell within the lung into a cancer cell,” says Dr. Yu.

Memories of exposures past — a model to study how DNA-associated epigenetic information is reproduced as cells multiply

Our bodies are made of 50 trillion cells, many of which continue dividing over our lifetime. According to Dr. Yu, how DNA-associated epigenetic information is reproduced and the factors that can alter this process are critical to understanding how disease may be triggered.

He and his colleagues recently developed a method called eSPAN, which stands for Enrichment and Sequencing of Protein-Associated Nascent DNA, to examine the mechanisms taking place as new cells are created. They published their findings in the journal Science.

“Epigenetic information carried by DNA-associated proteins needs to be copied from parent to daughter cells for passing down traits that distinguish different cell types. The same mechanisms also propagate effects of environmental exposures that may cause disease. Using yeast models, we can apply this new tool and observe how the proteins that carry epigenetic information are transferred to newly produced DNA strands and how gene mutations can influence these processes,” says Dr. Yu.

Using this new method, Dr. Yu and his team have observed the DNA replication process in a number of genes, including a gene linked to certain types of breast and prostate cancers in humans.

“We’ve observed genetic changes in the proteins regulating epigenetic inheritance that have been detected in some malignancies. Our goal is to uncover whether these DNA changes are in fact the cause or the consequence of cancer development”, says Dr. Yu.

As a next step, Dr. Yu and his colleagues plan to test the eSPAN method using human cells, hoping to uncover even more evidence of factors that lead to the development of disease.

The opportunity to reverse mechanisms driving disease

Dr. Yu expects the importance of epigenomics to continue to grow as more underlying biological and chemical mechanisms driving human disease are uncovered.

“DNA alterations can have lifelong implications to our health. In addition, some epigenetic alterations can be passed down from one generation to the next.  If we can understand why epigenetic alterations are occurring, we may be able to develop therapies that can reverse diseases by targeting these underlying mechanisms”, says Dr. Yu.

Join the conversation

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.


Dec 31, 2018 · The growing role of genetic nurses: educating, empowering patients

As genetic sequencing has become faster and cheaper, more people are considering predictive genetic testing to identify their future risk for disease, with the goal of taking charge of their health. Yet many face the challenge of understanding which genetic testing option would fit their health goals.

While genetic counselors have traditionally helped patients through this journey, there is a shortage of these professionals as genomics moves into more areas of clinical care.

That’s where Therese Hughes and Corinne Berg, genetic nurses in Mayo Clinic Center for Individualized Medicine,  step in, working with genetic counselors to educate and empower patients. Hughes and Berg are part of the care team for healthy patients in the Executive Health Program who are considering predictive genomic testing.

Teresa Kruisselbrink

“Over the last three years, we’ve added nurses to our team, developing a unique care model where they work together with genetic counselors to extend genomics education, and genetic testing when appropriate, to more patients. We’ve also shared our successful model with other institutions and professional organizations across the country,” says Teresa Kruisselbrink, genetic counselor and supervisor of genetic nurses in the Center.

Family trees – revealing clues about future health risks

As a first step in each appointment, Hughes and Berg map a patient’s family medical history.

Therese Hughes

“We’re looking for any clues that there may be a history of a medical condition that has a hereditary or genetic component – such as certain types of cancer, heart disease or neurological disorders, especially those experienced by family members before the age of 50. For example, if a family member died suddenly, it can be a sign of a hereditary heart disease or an increased risk for stroke,” says Hughes.

The nurses record medical histories for three or more generations of a patient’s family – that can include grandparents, parents, siblings and children.

Berg is inspired by her own personal story, which highlights the lifesaving information a family medical history can reveal.

“My aunt died at a young age from breast cancer. After learning about hereditary cancers in nursing school, I was tested and discovered I had the BRCA2 gene, which increases my risk for breast, ovarian and pancreatic cancer as well as melanoma. It turns out my mother and sister have the same gene. We all had mastectomies to prevent cancer from developing. My mother’s surgery revealed that she had an early stage breast cancer. Discovering I had the BRCA2 gene actually saved her life,” says Berg.

All three women continue to have regular cancer screening. “Knowing our family history and having genetic testing has enabled us to take charge of our health,” adds Berg.

Genetics 101 and testing options

Corinne Berg

Next, Hughes and Berg educate patients about the basics of genetics with materials they developed with staff in the Centers’ Education Program.

Patients learn about:

  • How genetic traits are passed down from one generation to the next
  • Genetic test options available, which range from genetic testing focused on genes known to have a link to disease risk to more comprehensive testing that assess a broader number of genetic characteristics

“We’re continually looking for ways to bridge the knowledge gap for patients. For example, we discovered that many male patients are unaware that BRCA1 or BRCA2 mutations could affect their own health or that of their family members. So we’ve developed materials to provide that information,” says Berg.

Spreading the word – educating nurses at the bedside about genomics

According to Hughes, the role of genetic nurses is likely to increase as genomics moves into more areas of health care. She and Berg attend monthly nursing practice meetings, spreading the word about the role of genomics in health and disease.

“By presenting and participating in these monthly meetings, we hope to inform nurses so they can understand the role genomics may play in their patients’ care. For example, nurses may be able to recognize when a patient has a family medical history or condition that warrants a consultation with a genetic counselor,” says Hughes.

The education will also help nurses understand pharmacogenomics information – how a person’s genetics may affect their response to medications. Mayo is at the forefront of moving this information into clinical practice.

“Pharmacogenomics data is being added to the electronic medical records of 10,000 Mayo patients participating in the RIGHT 10K study. Providers will receive an alert when prescribing a medication in which a patient’s genetics could cause serious side effects or require a dose adjustment. It is critical that both physicians and nurses carrying for these patients understand how pharmacogenomics can enhance individualized care,” explains Hughes.

To keep pace with the growing need for genetic nurses, both Berg and Hughes are pursuing additional training. Berg is earning a master’s in nursing education, and Hughes plans to become a nurse practitioner.

“We hope to play an even bigger role in guiding patients through their genomics journey,” explain Berg and Hughes.

Stay informed about individualized medicine

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Coverage from the 2018 Individualizing Medicine Conference:

Mayo Clinic Minute: What is the microbiome and how does it affect your weight?

Dec 3, 2018 · Meet Sanjay Bagaria, M.D.: new CIM associate director in Florida

Sanjay Bagaria, M.D.

Hindsight is 20/20.That saying rings true for surgical oncologist Sanjay Bagaria, M.D. As a premedical student at University of Michigan, he chose to major in Japanese studies, mastering thousands of characters and a new grammar structure to read the Japanese literature he loved. Looking back, that experience gave him the tools to view not only language, but eventually medicine, in new ways.

His research has focused on finding ways to boost the benefit that surgery provides patients with cancer. Now he’ll apply those lessons in his “dream job” as the new associate director, Center for Individualized Medicine(CIM), at Mayo Clinic’s campus in Florida.

“I am excited to join CIM and serve as a conduit for our talented clinicians and scientists in Florida, helping them turn ideas into discoveries that can improve individualized care. It’s an exciting time in precision medicine. We have the opportunity to bring together data from so many different areas to understand how genetic and biological processes drive disease. Our challenge is to harness this data to identify actionable steps to guide an individual’s medical care.” – Sanjay Bagaria, M.D.

“I am excited to join CIM and serve as a conduit for our talented clinicians and scientists in Florida, helping them turn ideas into discoveries that can improve individualized care,” says Dr. Bagaria. “It’s an exciting time in precision medicine. We have the opportunity to bring together data from so many different areas to understand how genetic and biological processes drive disease. Our challenge is to harness this data to identify actionable steps to guide an individual’s medical care.”

Boosting the benefit: surgery + chemotherapy in one procedure

Since joining Mayo Clinic in 2010, Dr. Bagaria has focused his clinical practice and research on a combined chemotherapy/surgical procedure called hyperthermic intraperitoneal chemotherapy (HIPEC) surgery, which is performed for select patients with late stage colon, ovarian and appendiceal cancer.

This individualized approach to cancer treatment involves surgically removing all visible cancer that has spread to the abdomen, and then, while in the operating room, bathing the abdominal cavity with heated chemotherapy for up to 90 minutes to kill any microscopic cancer cells that may remain. The type of chemotherapy given depends upon the patient’s cancer type.

According to Dr. Bagaria, the key advantage of this combined treatment is that a high dose of chemotherapy can be given to the area that needs it with minimal exposure to the rest of the body. This approach can often avoid the typical side effects of chemotherapy, such as hair loss, diarrhea and mouth sores.

While this therapy has helped some patients live longer, it doesn’t work for everyone. That’s why Dr. Bagaria has focused his research on ways to help more patients benefit from the treatment.

Dr. Bagaria is exploring:

  • Biomarkers, which are genetic variations that are already linked to certain cancer types , that may help predict whether a patient will respond to HIPEC therapy.
  • Other medications – such as immunotherapies that use the patient’s own immune cells to fight their cancer – that may be given either before or after HIPEC therapy to boost its effectiveness.

Early on – using research to improve surgical results    

“Throughout my career, I didn’t have a predetermined path. Instead, I followed my interests, letting each experience inform my next step,” says Dr. Bagaria.

After graduating from college, Dr. Bagaria worked for one year as an interpreter for government officials in Toga, a remote village near the Siberian coast of Japan. His job allowed him to travel  and welcome representatives from around the world.

Passing on a job as an interpreter at the 1998 Winter Olympics in Nagano, Japan, he attended Rutgers New Jersey Medical School and then completed a residency in surgery and post-doctoral training in genetic medicine at the Weill Cornell Medical College in New York.

“I chose surgery because it plays such a large role in curing diseases like cancer. During my surgical  fellowship at the John Wayne John Wayne Cancer Institute, I took a new approach to disease – looking at it from a medical viewpoint, not just a surgical one,” says Dr. Bagaria.

During his fellowship, Dr. Bagaria began work on developing a biomarker, which looked for a specific type of breast cancer known as basal-like breast cancer.

“We knew that basal-like breast cancer is highly aggressive and can respond to certain therapies.  We also knew that it is often confused with a type of breast cancer known as triple-negative breast cancer. The challenge was to discover a way to separate and easily identify basal-like breast cancer from triple-negative breast cancer,” he explains. Dr. Bagaria and his team identified a specific protein for basal-like breast cancer and developed a clinical test based on their findings.  He and three colleagues hold a patent for these discoveries.

“In my new role, I hope to pass along lessons I’ve learned in my own research and help investigators overcome obstacles, speeding the development of new predictive tools and therapies,” adds Dr. Bagaria.

A look into the future

So what does the future of precision medicine hold?

“Someday my own children will have their genetic and biological data used routinely to guide their medical care. CIM is uniquely poised to make this vision a reality – with research resources and experts across many disciplines, CIM has the ability to help Mayo Clinic physicians and scientists move ideas forward  that will improve prevention, diagnosis and treatment of disease,” says Dr. Bagaria.

Stay informed about individualized medicine

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Coverage from the 2018 Individualizing Medicine Conference:



Nov 5, 2018 · Pharmacogenomics: finding the right drug, dose for cancer therapy

Robert Diasio, M.D.

Each year, nearly 300,000 patients receive the lifesaving chemotherapy 5-fluorouracil (5-FU) to treat many types of cancer, including colorectal, breast, bowel, skin, pancreatic, and esophageal cancer. While it can be an effective treatment, it doesn’t work for everyone. In fact, up to 30 percent of those who receive the standard dose can have serious, life-threatening side effects.

Robert Diasio, M.D., director, Mayo Clinic Cancer Center, has uncovered genetic variations that cause some patients to experience these serious side effects. Now using pharmacogenomics testing, which looks at how a person’s genetic traits affect their medication response, and a new gene verifier model, Dr. Diasio and his colleagues are able to test and find a safe, alternative 5-FU dose, allowing these patients to get the benefit of treatment, without harmful side effects.

“While a standard dose of 5-FU can be very effective in treating many cancers, it is challenging to predict who will have serious side effects from the therapy. That’s because genetic testing prior to therapy is not mandatory. Therefore, we’re only able to identify these patients after they’ve had therapy and experienced severe complications,” says Dr. Diasio.

A tool to identify a safe, alternative dose  

Through his laboratory research, Dr. Diasio has uncovered genetic variations in the DPYD gene that help drive how a patient processes the 5-FU therapy.

His gene verifier tool has already helped redirect care and individualize therapy for a patient with rectal cancer.

Only 5 days after starting 5-FU therapy to shrink his tumor before surgery, the patient experienced extreme fatigue, severe diarrhea and a skin rash. He was hospitalized and had to stop treatment.

Pharmacogenomics testing revealed that he had one common DPYD variant known to cause complications, along with a rare genetic mutation that may also be interfering with how he processed the medication.

Using the new model, Dr. Diasio and his colleagues were able to understand how both the common and rare variant caused the patient to process 5-FU more slowly, causing debilitating side effects.

“For this patient, the standard 5-FU dose caused an overdose of medication that was not only fighting his cancer cells, but also damaging the normal cells in his bone marrow and nervous system. Based on our model, we calculated that his dose should be reduced by 75 percent – this is a dose that physicians would never have considered without pharmacogenomics and genetic analysis,” says Dr. Diasio.

The adjusted dose allowed the patient to receive the therapy he needed after surgery to prevent the cancer from returning, with fewer side effects. Dr. Diasio and his colleagues recently published these results here.

Pharmacogenomics – helping target therapies for patients

This is just one example of how pharmacogenomics helps individualize cancer therapy for patients. It can also help physicians select from among many different therapies to target the unique genetic characteristics of a patient’s cancer.

“Our pharmacogenomics research has shown that many factors contribute to medication response and one of those is genetics. We’ve also identified how differences among ethnic groups affect response to medications like 5-FU. For example, 3 to 5 percent of Caucasians carry one DPYD gene variant that causes serious side effects, while those from African descent carry a different variant with the same risk for complications,” says Dr. Diasio.

“As new genetic variants linked to cancer and medication responses are discovered, we’ll continue to refine our individualized treatments directed at each patient’s disease.”

Learn more about pharmacogenomics

Join Center for Individualized Medicine for Drugs and Genes: Pharmacogenomics for the Modern Health Care Team 2018 on Nov. 30-Dec. 1 in Scottsdale, Arizona. The course is designed for physicians, pharmacists, nurses and genetic counselors to provide an overview of how pharmacogenomics is being used to help individualize patient care.

Read about how Mayo Clinic is moving pharmacogenomics into every day clinical care with Mayo Clinic RIGHT 10K study. 

Stay informed about individualized medicine

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Coverage from the 2018 Individualizing Medicine Conference:

Oct 15, 2018 · Personalized screening: finding and treating breast cancer sooner

Deborah Rhodes, M.D.

October is Breast Cancer Awareness Month, a time to reflect on new, individualized approaches to detecting and treating a cancer that affects 1 in 8 American women. Deborah Rhodes, M.D. and her Mayo Clinic colleagues are working to identify the best targeted screening tools and guidelines for women with a higher risk of developing breast cancer – those with dense breast tissue and those with an inherited genetic variation linked to the disease.

With support from the Center for Individualized Medicine, Dr. Rhodes and her colleagues have developed research to find the best way to screen for breast cancer in these populations, with the goal of detecting and treating the disease sooner.

“It’s critical to detect breast cancer early because survival is linked to tumor size at the time a patient is diagnosed. If we discover a tumor when it is less than one centimeter, that patient has over a 90 percent chance of surviving. That’s why we are evaluating how to use new imaging techniques and genetic tests to provide the best care for patients who are at higher risk of developing breast cancer.” – Deborah Rhodes, M.D.

“It’s critical to detect breast cancer early because survival is linked to tumor size at the time a patient is diagnosed. If we discover a tumor when it is less than one centimeter, that patient has over a 90 percent chance of surviving,” says Dr. Rhodes, a Mayo Clinic Breast Clinic physician. “That’s why we are evaluating how to use new imaging techniques and genetic tests to provide the best care for patients who are at higher risk of developing breast cancer.”

Evaluating screening tools for women with dense breast tissue

According to Dr. Rhodes, the 27.6 million women in the U.S. who have dense breast tissue may not be effectively screened with mammography alone. Many states have laws that require physicians to notify women if they have high breast density and how this affects breast cancer detection and risk.

As Dr. Rhodes explains, “We want to build awareness so that women understand that high breast density is the primary reason for missed or delayed breast cancer detection. Dense breast tissue can mask cancer tumors on mammography. Since high breast density increases a woman’s risk of developing breast cancer, it’s important that we find effective screening methods to identify the cancer early, when it is most treatable,” says Dr. Rhodes.

Since there are no consensus guidelines on how best to screen these patients, Dr. Rhodes and her colleagues are conducting a comprehensive evaluation of two screening approaches – 3-D mammograms and molecular breast imaging (MBI).

3-D mammograms have replaced 2-D mammograms as the standard screening tool in many centers. Research has shown that the main benefit of a 3-D mammogram is that it reduces the chance that a patient will be recalled for additional testing because of findings that are false positives and not due to cancer.

“MBI has been shown to more clearly distinguish between dense breast tissue and tumors. In a Mayo Clinic study, MBI detected more than three times the number of cancers compared to 2-D mammograms. We’re exploring whether MBI provides this same advantage over 3-D mammograms,” says Dr. Rhodes.

In addition to comparing cancer detection rates, the Mayo MBI research team is also analyzing the costs associated with each screening method.

Carrie Hruska, Ph.D.

“One of the advantages of MBI is that it can be performed at a relatively low cost, comparable to the cost of a mammogram, and many insurance carriers are starting to cover MBI for screening,”says Carrie Hruska, Ph.D., a Mayo Clinic physicist. “In current trials, researchers are tracking the costs of MBI screening as well as costs of downstream testing generated by findings on MBI and 3-D mammograms in order to compare their cost-effectiveness.”

The team is also addressing a common concern about the higher radiation dose used in MBI, compared to 3-D mammograms. Dr. Hruska and physicist Michael O’Connor, Ph.D. have made several modifications to the MBI system to permit the exam to be performed at a low radiation dose that is safe for routine screening.

The researchers are aiming to lower the radiation dose even further to the same level as a mammogram by applying an image processing algorithm to reduce “noise” in the MBI images. In preliminary studies, using this mathematical model allowed radiation dose to be cut in half, yet the ability to detect breast cancers was preserved.

“We’re carefully evaluating both screening tests and hope to have substantial data to support cancer screening recommendations for patients with dense breast tissue – recommendations that are needed to save lives through earlier detection and treatment,” says Dr. Rhodes.

Hereditary breast cancer – guidelines for a lifetime of care

Mayo researchers and physicians are also collaborating to streamline care for patients whose breast cancer is linked to inherited genetic mutations. A finding of hereditary cancer could lead to changes in treatment, and it could alert other family members that they may also be at a higher risk of developing breast cancer.

Along with Myra Wick, M.D., Ph.D., Dr. Rhodes is co-chair of the Mayo Clinic Familial Cancer Cross Disciplinary Disease Group. The group brings together experts from many specialties –radiology, genetics, surgery, gynecology, oncology, endocrinology, laboratory medicine, pathology and primary care. Their goal is to identify the best care guidelines for patients who either have or are suspected to have a genetic variant linked to hereditary cancer.

“Whether these patients have already been diagnosed with hereditary breast cancer or have a family history suggesting they may have a hereditary breast and ovarian cancer syndrome, we want to identify the best care pathway for them. We’re mapping each patient scenario to determine how to guide their medical care over a lifetime,” says Dr. Rhodes.

Learn more about individualized medicine

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

See highlights from Individualizing Medicine: Advancing Care Through Genomics, which was held Sept. 12-13 in Rochester, Minnesota:



Oct 4, 2018 · Meet Lisa Schimmenti: Searching for drug therapies to treat hearing loss

Lisa Schimmenti, M.D.

Lisa Schimmenti, M.D. has always been fascinated with Helen Keller and all she accomplished, in spite of being blind and deaf from a very young age. As the newly appointed chair of Mayo Clinic’s Department of Clinical Genomics and a medical geneticist, Dr. Schimmenti cares for patients with similar conditions.

In her clinical practice, she sees children and adults with Usher syndrome, a rare genetic condition that causes deafness or profound hearing loss at birth and blindness by the time a child turns five. With support from the Center for Individualized Medicine and the Department of Otorhinolaryngology, Dr. Schimmenti is using zebrafish to search for drug therapies that could help restore hearing for these patients.

During her career, she’s seen how genomic discoveries have uncovered the causes of many rare diseases and led to the development of new targeted treatments for many more common diseases like cancer and heart disease. Now in her new role overseeing the Department of Clinical Genomics, Dr. Schimmenti is working to extend genomics medicine across all specialties at Mayo Clinic.

“Our clinical geneticists and genetic counselors are collaborating with all departments to facilitate the use of the latest genomic testing technologies to help improve care for all patients.” – Lisa Schimmenti, M.D.

“Our clinical geneticists and genetic counselors are collaborating with all departments to facilitate the use of the latest genomic testing technologies to help improve care for all patients,” says Dr. Schimmenti.

Here’s a closer look at how she’s using the latest genomics tools in her own research to uncover a treatment for hearing loss.

Restoring hearing to boost language development

For newborns diagnosed with Usher syndrome, the only current treatments available for hearing loss are devices such as hearing aids or cochlear implants. However, cochlear implants cannot be implanted until an infant is 12 months old and many infants do not benefit from a hearing aid alone.

“If we can identify a drug to improve hearing, we can help newborns hear sooner, at a time when language development is so critical. They may then be able to use a hearing aid while awaiting a cochlear implant,” says Dr. Schimmenti.

Zebrafish – the perfect model for drug discovery

Dr. Schimmenti and her team are using zebrafish, a type of freshwater fish, to test drug compounds to improve hearing.

“We are able to use zebrafish to model the conditions that we see in the clinic because they share 70 percent of their genes with humans. The same gene that causes Usher syndrome in humans also causes the syndrome in zebrafish,” says Dr. Schimmenti.

The research team tests different therapies by putting the medication into the water. They then measure changes in the hair cells on the zebrafish, which are an important link in the sensory process for hearing, to identify any changes.

The team’s early research results are promising. The next step is to test therapies that have been shown to improve hearing in mouse models.

“While we are early in the research process, the prospect of finding a drug to bypass some of the genetic defects in the sensory process that are causing deafness is very exciting. It’s possible that these therapies could also be applied to treat hearing loss caused by other conditions. For example, some cancer treatments can cause nerve damage and hearing loss. The implications of these discoveries could eventually be far reaching.” – Dr. Schimmenti

“While we are early in the research process, the prospect of finding a drug to bypass some of the genetic defects in the sensory process that are causing deafness is very exciting. It’s possible that these therapies could also be applied to treat hearing loss caused by other conditions. For example, some cancer treatments can cause nerve damage and hearing loss. The implications of these discoveries could eventually be far reaching,” says Dr. Schimmenti.

A passion for genetics

Dr. Schimmenti became interested in genetics early in her medical training. However, she chose a different path before returning to genetics as the focus of her career.

“During my pediatrics training at Harbor-UCLA Medical Center, I saw many young patients with severe hearing loss and was surrounded by outstanding mentors who were working to uncover the genetic causes of these conditions. But at the time, the Human Genome Project, the first mapping of an entire human genome, had not been completed. Genomic discovery was in the early stages, so I chose to pursue a fellowship in critical care at Yale University rather than continue in genetics,” says Dr. Schimmenti.

As progress in genomic discovery continued and genetic variants linked to hearing loss were identified. Dr. Schimmenti decided to return to her true passion – working in the lab to uncover new therapies for the patients with rare genetic diseases that she cared for in the clinic.

She returned to University of Minnesota to complete her genetics fellowship and begin her work using zebrafish to better understand the genetic and molecular processes driving hearing loss.

And she’s never looked back.

“It’s exciting to use genomics to search for a drug that could treat hearing loss and make a real difference for patients. At the same time, I am excited to collaborate with all medical specialties across Mayo Clinic to see how we can extend genomics services to all patients and enhance individualized care for many conditions,” says Dr. Schimmenti.

Learn more about individualized medicine

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

See highlights from Individualizing Medicine: Advancing Care Through Genomics, which was held Sept. 12-13 in Rochester, Minnesota:

Sep 17, 2018 · CIMCON18 -- how genomics discovery is transforming individualized care and the path forward

Moderator Cathy Wurzer and Keith Stewart, M.B., Ch. B.

Mining information deeper than genomics, understanding factors linked to disease, analyzing big data, and addressing the challenges of bringing all this information together to advance patient care – these were some of the themes featured at the Individualizing Medicine Conference: Advancing Care through Genomics held in Rochester, Minnesota, Sept. 12-13, and sponsored by the Mayo Clinic Center for Individualized Medicine.

Keith Stewart, M.B., Ch.B., the Carlson and Nelson endowed director, Mayo Clinic Center for Individualized Medicine, opened the conference by explaining genomics discovery is moving rapidly and the conference gives a glimpse of the exciting research taking place along with how it is already improving patient care.

Here are some of the highlights from this year’s plenary speakers, all bringing their expertise to drive precision medicine forward.

The genomics landscape – from the Human Genome Project to next steps for future discovery

Eric Green, M.D., Ph.D.

Eric Green, M.D., Ph.D., director, National Human Genome Research Institute  at the National Institutes of Health (NIH) traced the advances of genomic testing since it was discovered three decades ago. Chief among them is the landmark completion of the Human Genome Project in 2003, which sequenced the first human genome. Since then, Dr. Green says, the cost of genomic sequencing has dropped by 1 million fold, and it can be done in weeks or days in some labs He also spotlighted key advancements:

  • Uncovering genetic links to cancer
  • Understanding drug-gene interactions through pharmacogenomics
  • Using genomic testing to identify more than 4,000 rare genetic diseases
  • Advancing prenatal care so the health of the baby can be assessed through genetic testing from the mother’s blood, rather than with invasive tests like amniocentesis

Now genomic testing is moving from the research setting into clinical practice. Dr. Green and his team forecast that by 2022, more than 80 percent of genetic testing will take place in the health care system. This trend is one of many factors Dr. Green and his team are considering as they develop a 2020 strategic plan for advancing genomics, gathering input from the broad scientific, health care and patient communities.

Dr. Green also highlighted the National Institutes of Health All of Us Research Program, an unprecedented national research  program that kicked off in May.  All of Us  is enrolling a million people into a research cohort to advance an individualized approach to managing health and disease. Mayo Clinic is home of the biobank that will store biospecimens for the All of Us Research Program.  As of August 2018, Mayo had stored nearly 1.7 million samples from more than 57,000 participants.

Moving pharmacogenomics into daily clinical care

Richard Weinshilboum, M.D.

According to Richard Weinshilboum, M.D., pharmacogenomics is the first area of precision medicine that will be integrated into patient care daily, and predicts that it will, eventually touch every patient everywhere.

Dr. Weinshilboum is co-director of the Mayo Clinic Center for Individualized Medicine Pharmacogenomics Program and a pioneer in the field of pharmacogenomics, which explores how a person’s genetic characteristics affect their response to medications.

At the conference, Dr. Weinshilboum shared the promise and challenges of implementing pharmacogenomics into daily clinical practice. He highlighted Mayo’s RIGHT 10K study, which will add preemptive pharmacogenomics test results for 10,000 Mayo Clinic Biobank patients into their electronic health record.

The goal is to understand how  having this genetic information available at the point of care may help improve care.  The idea is that this information will guide health care providers to identify medications and/or make dose adjustments that are compatible with a patient’s genetic makeup, maximizing the therapy benefit and reducing harmful side effects.

Uncovering the mechanisms driving disease

Manolis Kellis, Ph.D.

Manolis Kellis, Ph.D. is going beyond genomics to understand the processes driving disease. Dr. Kellis, a computational biologist at Massachusetts Institute of Technology (MIT) and the Broad Institute, and his team have developed maps to understand how genetic variations and other biological and molecular processes contribute to many diseases, including heart disease, Alzheimer’s, cancer and obesity.

This groundbreaking approach has uncovered some surprising results. For example, Dr. Kellis and his team found that the strongest genetic association with obesity acts via a master switch controlling energy storage and expenditure, rather than through the control of appetite in the brain. This finding suggests that there is more to controlling weight than watching your diet and getting regular exercise.

Mining biobank and electronic health record data to uncover genetic links to common diseases

Nancy Cox, Ph.D.

While it is exciting to have additional information about patients – their genomic test results, biological data and health history, how can researchers interpret that information so that it can improve a patient’s care?

Nancy Cox, Ph.D. and her team are addressing this challenge with computer models. Dr. Cox, director, Vanderbilt University Genetics Institute and Division of Genetic Medicine, is using these tools to analyze genetic test results from biobank participants, along with data from their electronic health records to better understand a patient’s risk for disease.

As Cox explained, the advantage of this approach is it allows researchers to look across all of the diagnoses associated with a specific gene at the same time, rather than the traditional approach of focusing on one disease. This uncovers conditions or symptoms that may help predict disease, prompting earlier screening and treatment. They’ve developed a publically available catalog of these associations, which include not only genomic but other biological and environmental factors that can help predict disease.

Imaging biomarkers to predict disease

Gabriel Krestin, M.D., Ph.D.

Gabriel Krestin, M.D., Ph.D. is also developing models to predict disease and has been a leader in combining imaging methods with genomic, biological and environmental data to identify subtle changes linked to disease risk.

Using artificial intelligence to analyze data from large-scale population studies of healthy individuals, he and his team have identified imaging biomarkers to predict complex diseases such as dementia and Alzheimer’s.

Their findings are being used to help detect and treat disease sooner.

Dr. Krestin is chairman, Department of Radiology and Nuclear Medicine at Erasmus MC, University Medical Center Rotterdam, in the Netherlands.

Michael Berger, Ph.D.

MSK-IMPACT – large scale genomic testing to guide cancer care

Michael Berger, Ph.D. has made great strides in expanding the search for genetic links to cancer. Dr. Berger, a geneticist at Memorial Sloan Kettering (MSK), and his team developed MSK-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a genetic test that looks across 468 genes associated with both rare and common cancers.

By using MSK-IMPACT to screen more than 20,000 MSK patients with advanced cancer, Dr. Berger has created the largest gene panel database.

Berger highlighted how this testing has changed the course of treatment for patients. For example, MSK-IMPACT testing revealed that a woman previously thought to have metastatic breast cancer actually had cancer that originated in her lungs. As a result, her treatment was changed from hormone therapy to the appropriate chemotherapy.

Test results are also helping direct patients to clinical trials based on the genetic characteristics of a patient’s tumor, rather than where the tumor originated.

CAR T-cell therapy – reengineering immune cells to fight cancer

Yi Lin, M.D., Ph.D.

Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is a new immunotherapy that reengineers a patient’s own immune cells to create a  living drug that recognizes and fights a patient’s cancer. The therapy is currently approved to treat patients with B-cell non-Hodgkin’s lymphoma and B-cell acute lymphocytic leukemia (ALL) who have not responded to standard therapy.

Yi Lin, M.D., Ph.D., a hematologist at Mayo Clinic’s campus in Rochester, Minnesota, and chair of the Cellular Therapeutics Cross-Disciplinary Group in the Mayo Clinic Cancer Center, shared promising clinical trial results where the majority of patients responded to this new, individualized treatment. She also explained that it is most appropriate for patients whose disease has stabilized and who can handle the range of side effects that may come with this treatment.

Next steps – expand collaboration, build evidence and boost genomic literacy

Heidi Rehm, Ph.D.

Heidi Rehm, Ph.D., wrapped up the conference  with a presentation on collaboration and data standards that are keys to improving the rate of diagnosing rare, genetic diseases. Dr. Rehm has championed many efforts to discover and share disease-related variants in order to move genomics into clinical care.

Dr. Rehm is a geneticist and genomic medicine researcher at the Broad Institute Chief Genomics Officer at Massachusetts’s General Hospital and Professor of Pathology and Harvard Medical School.

Timothy Curry, M.D., Ph.D. and Cathy Wurzer

So what are the next steps in genomics?

“We need to expand these collaborations to build the critical evidence needed to translate genomics into better prevention, screening and treatment for patients. We’re also working to boost genomic literacy so that physicians and patients understand how genomics,  along with other clinical information, can enhance patient care ,” says Timothy Curry, M.D., Ph.D., director, Mayo Clinic Center for Individualized Medicine Education Program.

More conference highlights

Up next – pharmacogenomics for the modern health care team

Mark your calendar and plan to join us at Drugs and Genes: Pharmacogenomics for the Modern Health Care Team 2018 in Scottsdale, Arizona from Nov. 30 to Dec. 1, 2018.

Keep the conversations going

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.



Sep 4, 2018 · Preemptive genetic testing: could it help you take charge of your health?

Konstantinos Lazaridis, M.D.

A blood pressure check, an immunization and a cholesterol test – these are all parts of your routine medical care. Someday, a genetic test to identify your risk for developing disease may also be added to the list. In fact, researchers believe that day is fast approaching thanks to the rapid advances in genomic medicine.

That’s why Konstantinos Lazaridis, M.D. and his research team are exploring how healthy people may benefit from preemptive genetic testing. The goal of their research is to learn more about how using whole genome sequencing (WGS), a type of genetic test, with healthy individuals may:

  • Affect health outcomes
  • Impact healthcare use
  • Affect behaviors and feelings of those who undergo WGS testing

“There are approximately 60 known genetic mutations linked to an increased risk of developing specific diseases. This number will most likely grow as precision medicine research advances. Yet there is very little research on the benefit that preemptive WGS testing may offer healthy individuals, who have no known signs or symptoms of disease. With a one-time WGS test, patients may learn information that could help them take charge of their health and help physicians guide their medical care over a lifetime,” says Dr. Lazaridis, associate director, Mayo Clinic Center for Individualized Medicine.

Who will benefit most?

Dr. Lazaridis and his team want to study WGS testing results from 500 people, all participants in the Mayo Clinic Biobank. He and his team are hoping to describe the frequency that healthy individuals bear disease causing genetic variants and identify whether certain groups have higher rates of genetic variants linked to disease risk.

“Our research results may help us detect those healthy individuals who would benefit most from preemptive genetic testing. For example, we may find that those participants with a family history of a specific disease have a higher likelihood of having a relevant genetic mutation that puts them at risk for developing the same condition,” says Dr. Lazaridis.

The ripple effect – how will genetic information impact patients, their families?

According to Dr. Lazaridis, his team is also exploring the psychological and social implications that genetic test results may have on patients and their families.

“We may have participants who learn they have a genetic mutation such as BRCA1 or BRCA2, both associated with an increased risk for breast and ovarian cancer. As part of our research, we plan to conduct periodic surveys to assess how this information impacts these individuals’ future decisions about screening and treatment. We also want to learn how this new knowledge affects the decisions of their family members. For example, did other family members choose to have genetic testing?” says Dr. Lazaridis.

Knowledge is the key – for patients and providers 

How can we better understand and act on the preemptive WGS test results as patients and health care providers? That’s a question that Dr. Lazaridis and his team are answering through genomics education for participants and the physicians who care for them.

“We’re working closely with primary care providers to educate them on how to interpret and apply WGS test results, along with other clinical results, to guide patient care,” explains Dr. Lazaridis.

The team has developed educational materials for patients that explain how genomic testing works and how test results may be used to direct their medical care now and in the future.

“The test results of each study participant will become part of their electronic health record and subjects with medically actionable findings will have proper follow up and clinical care. As new genomics discoveries are made in the future, these genetic results may even become more impactful in managing care over their lifetime,” says Dr. Lazaridis.

Join the conversation

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Register to attend this year’s Individualizing Medicine Conference. It will be held in Rochester, Minnesota, on Sept. 12-13, 2018.

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