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Thu, Nov 15 6:00am · Meet Lisa Schimmenti: Searching for drug therapies to treat hearing loss

This article originally appeared on the Center for Individualized Medicine blog on Oct. 4, 2018

Article by Sharon Rosen


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:

Tue, Nov 6 6:00am · Mayo Clinic research combines genetics and psychiatry to seek biomarkers for precise alcohol abuse therapies

This article originally appeared on the Center for Individualized Medicine blog on Oct. 23, 2018.

Mayo Clinic research is bringing together knowledge of psychiatry, genetics, metabolomics, pharmacogenomics and artificial intelligence to seek biological markers associated with alcohol use disorder and treatment response. Finding the molecular drivers of alcohol use disorder commonly known as alcoholism, could help predict who is most likely to develop this disorder and who might respond to medications approved for treatment. It might also reveal insights into new medications when standard drugs don’t work and could guide health care providers to precise treatments.

Victor Karpyak, M.D., Ph.D.

“Alcohol use disorder is one of the most prominent mental health problems in the world, second only to depression in terms of burden of disease,” says Victor Karpyak, M.D., Ph.D., a Mayo Clinic psychiatrist, co-principal investigator and leader of the integrated study team. “Only about 10 percent of those with alcohol use disorder seek therapeutic help. We believe that’s because people don’t expect medications to be efficient and helpful in treatment, which is unfortunate and factually incorrect.”

The Food and Drug Administration has approved three medications for treatment of alcohol use disorder. However, they don’t work for everyone. There are no known biomarkers that reliably predict which patients would be good candidates for these therapies.

“Tragically, there are some people who have biological characteristics which make them more susceptible to  alcoholism. What we’d like to do is better understand the genetic and molecular underpinnings of this susceptibility, so we can understand drug response and take an individualized approach to helping these patients overcome alcohol use disorder,” says Richard Weinshilboum, M.D., one of the researchers involved in this project and co-director of the Mayo Clinic Center for Individualized Medicine Pharmacogenomics program.

In a team science approach, Mayo Clinic will launch a coordinated study in conjunction with and funded by two National Institute on Alcohol Abuse and Alcoholism grants. The study will focus on the search for genetic markers of response to the drug acamprosate, which has been shown to help alcoholics stay sober.

“For some of our patients, the medicine known as acamprosate is a remarkably effective supplement to the clinical therapy and peer support, helping to curb cravings during and after treatment,” says Marvin D. Seppala, M.D., chief medical officer of the Hazelden Betty Ford Foundation, which is collaborating on the study. “Unfortunately, we have no idea who it will work for and who it won’t, so we just provide it to patients and hope that it helps.”

The five-year study expands previous pharmacogenetic research completed by the Mayo Clinic Department of Psychiatry by scanning the entire genome and metabolome in search for biological markers — clues to disease cause and treatment.

“Knowledge of the biology of alcohol use disorder and response to medication may allow us to zero down on meaningful molecular targets and see how we can intervene with genetic manipulations or new medications to reduce a person’s vulnerability to this disease,” says Dr. Karpyak.

Applying pharmacogenetics for an individualized treatment approach on a large scale

Researchers will follow 800 people receiving care for alcohol use disorder through Mayo Clinic affiliates as well as at the Hazelden Betty Ford Ford Foundation’s residential treatment facility in Center City, Minnesota. Study participants will have genetic testing to identify variants to help predict their response to the use of acamprosate or placebo.

The study will then combine pharmacogenomics — how the body processes and responds to medication — and metabolomics — small molecules known as metabolites that interact in the body — to try to better understand why the drug works for some but not others.

Richard Weinshilboum, M.D.

“We will look at the metabolites in their blood and bring together metabolomics with genomics. We hope that using the drug as a molecular probe will help us determine if there are different genes that might affect how each individual responds to anti-alcohol therapy,” says Dr. Weinshilboum, co-principal investigator of this study. “When we have used this approach before for psychiatric diseases like depression, we identified genes that we had never heard of before that appeared to be related to drug response, and then we used artificial intelligence and machine learning techniques to incorporate that information into a predictive algorithm.”

Researchers hope that if they find new genes linked to alcoholism treatment response, they might be able to identify new therapies compatible with a patient’s genetic fingerprint. That’s important in part because alcohol use disorder is linked to a number of other mental health conditions as well as conditions such as fetal alcohol spectrum disorders, hypertension, cardiovascular diseases, type 2 diabetes and liver cirrhosis.

This study  reflects many years of collaborative work and support between the Mayo Clinic Department of Psychiatry and Psychology, the Mayo Clinic Center for Individualized Medicine Pharmacogenomics Program, and the Samuel C. Johnson Genomics of Addiction Program.

Beside Dr. Karpyak and Dr. Weinshilboum, the study team includes:
Joanna Biernacka, Ph.D., co-principal investigator
Doo-Sup Choi, Ph.D., co-principal investigator
Mark Frye, M.D. chair, Mayo Clinic Department of Psychiatry and Psychology

The research team would like to give special recognition to the late David Mrazek, M.D., upon whose pioneering work this study builds.




If you’d like to learn more about pharmacogenomics and its broader applications, Dr. Weinshilboum will be a featured speaker at “Drugs & Genes: Pharmacogenomics for the Modern Health Care Team, Nov. 30 – Dec. 1, 2018 in Arizona. Sponsored by the Center for Individualized Medicine, “Drugs & Genes” will be held at the Scottsdale Marriott in Scottsdale, Arizona.




Join the conversation

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:

Wed, Oct 24 6:00am · Bringing pharmacogenomics to your medical practice

After decades of research, pharmacogenomics is “ready for prime time” so to speak. Mayo clinic is a leader in moving pharmacogenomics into clinical care with the goal of helping providers identify medications that are compatible with their patients’ genetic profiles. Drugs and Genes: Pharmacogenomics for the Modern Health Care Team 2018 is an opportunity to learn from the experts at Mayo Clinic. The two-day course, sponsored by Mayo Clinic Center for Individualized Medicine, will be held in Scottsdale, Arizona on Nov. 30 and Dec. 1. Drugs and Genes will provide an introduction to the basic science of pharmacogenomics and information on how you may integrate it into your daily practice.

Fadi Shamoun, M.D.

Mayo Clinic experts in pharmacogenomics will share knowledge, personal experience, and case studies. One of the presenters will be Fadi Shamoun, M.D., a consultant and assistant professor in the Department of Cardiovascular Diseases at Mayo Clinic’s campus in Arizona. Dr. Shamoun will speak about pharmacogenomics, not only from a clinician’s perspective, but also from that of a patient. He learned the personal value of pharmacogenomics when he went through pharmacogenomics testing himself. His test results turned him into a true believer in the value of pharmacogenomics drug-gene testing.

“I knew that pharmacogenomics tests were used to help physicians select the right drug and right dose for patients. But I was still skeptical. However, I had an ‘aha moment’ when I saw my own test results revealed a sensitivity to Warfarin, a blood thinning medication used for patients with heart disease. As a cardiologist, I deal with this drug every day but never knew how it might affect me. I learned if I ever take this drug, my dosage would need to be adjusted to avoid side effects such as severe bleeding. I am now a true believer in the importance of pharmacogenomics,” says Dr. Shamoun.

For a full list of presenters, and to register, visit the Drugs and Genes website.



Mon, Oct 22 6:00am · Personalized screening: finding and treating breast cancer sooner

This article originally appeared on the Center for Individualized Medicine blog on Oct. 15, 2018.

Article by Sharon Rosen

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:



Thu, Sep 20 6:00am · Gerstner awards boost research into hereditary cancer, Parkinson's disease

This article originally appeared on the Mayo Clinic Center for Individualized Medicine blog on August 27, 2018

Creating tools to detect cancer at an early stage and advancing research into the genetic links to Parkinson’s disease are focuses of the 2018 Gerstner Family Career Development Awards. This year’s winners are Niloy ‘Jewel’ Samadder, M.D., a gastroenterologist at Mayo’s Arizona campus whose research focuses on inherited cancer, and Fabienne Fiesel, Ph.D., a neurosciences investigator at Mayo’s Florida campus.

The Gerstner Family Career Development Awards in Individualized Medicine are given each year to early-stage investigators to advance individualized therapies. The award provides funding for research that furthers an individualized approach to predicting, preventing, treating and possibly someday curing disease. Another goal is to promote a specialized workforce capable of moving individualized medicine from discovery into patient care.

Niloy ‘Jewel’ Samadder, M.D.: Genetic testing as a screening tool

As a young physician-researcher, Dr. Samadder treated many young people with early onset cancers — the types that are passed down in families. These patients had a specific inherited gene that increased their chances of developing cancers throughout their body. People with inherited cancer genes often undergo an extensive battery of screening procedures every year including colonoscopy, endoscopy, ultrasounds and even preventative prophylactic surgeries. That inspired his current research to develop tools to non-invasively screen for multiple cancers for those at highest risk. Dr. Samadder envisions a tool similar to Cologuard®, a stool-based test developed at Mayo Clinic. His research will focus on designing a unique stool or blood test that could help detect a cancer at a very early stage anywhere in the body at a point when it is most curable.

Niloy “Jewel” Samadder, M.D.,

“Our goal is to develop a noninvasive, blood-based or stool-based tool that can be applied to hereditary cancers for patients who are at risk of multiple cancers,” says Dr. Samadder. “This is more likely to be accepted and completed by the patient. These tools could also make it easier for family members to be screened and learn who else is at a higher risk for hereditary cancer.”

Research shows that up to one in every five cases of cancer is linked to inherited mutations. As many as half of those cases are missed by current screening guidelines. Even after these patients are diagnosed with an inherited or genetic form of cancer, their screening can be complex and therefore, hard to follow. Additional tools may address that issue by providing new, less invasive screening options. For example, guidelines call for patients with Lynch syndrome, a genetic condition that comes with a high risk of colon, endometrial, ovary, stomach and other cancers – to have colonoscopies, and other time consuming screenings every year for the rest of their lives. Could a stool- or blood-based test to detect cancer be used as an alternative?

“It may not replace colonoscopy or other currently recommended tools completely in this high risk population, but instead of getting a colonoscopy every year, if this test is reasonably good, it could take the place of colonoscopy every other year,” says Dr. Samadder.

His research will focus on screening for inherited mutations in the following groups of cancers:

  • Colon
  • Uterine
  • Lynch syndrome
  • Breast/ovarian
  • BRCA syndrome
  • Duodenal

The Gerstner Award will allow him the time and opportunity to tap the expertise of others at Mayo Clinic in his research. This project has the potential to transform the care of patients with inherited forms of cancer and provide an individualized medicine approach to cancer prevention and early detection.

Fabienne Fiesel, Ph.D.: Seeking new therapies for Parkinson’s disease

Dr. Fiesel’s research seeks to discover new biomarkers — indicators of health and disease — with the ultimate goal of preventing, treating and curing Parkinson’s disease through precision medicine. Currently, there are approved therapies to treat the symptoms, but there is no known therapy or cure for the disease itself.

Her research centers on a fundamental cell biology pathway that links two genes involved in rare hereditary forms of Parkinson’s. Mutations in PINK1 and Parkin result in the accumulation of damaged mitochondria and lead to the death of the nerve cells, which causes loss of bodily function. Mitochondria are the powerhouse of a cell, acting like an energy source that keeps cells alive.

Fabienne Fiesel, Ph.D.

“There is evidence that mitochondrial damage is also linked to non-inherited forms of Parkinson’s and it is an early marker for several other (neurodegenerative) diseases,” says Dr. Fiesel. “A lot of research is being done to understand the biology of this pathway and to develop specific treatments to prevent mitochondrial damage.”

Dr. Fiesel’s team will perform deep molecular analysis, comparing cells with genetic mutations to cells of healthy people. She hopes to find a biomarker that will help to identify mitochondrial problems in Parkinson’s disease patients. This biomarker will be useful to test whether a specialized diet and exercise to improve the health of mitochondria, can have therapeutic benefits and whether specific therapeutic agents can be identified to correct or slow advancement of the problem.

“Hopefully someday we will be able to identify mitochondrial damage before a person has Parkinson’s or any other disease and before there is nerve damage. Then, maybe we could intervene with treatment before there is death of neurons and disease,” says Dr. Fiesel, “but this is only the beginning of our research.”

Dr. Fiesel’s project seeks to identify which Parkinson’s disease patients might be prime candidates for mitochondrial therapies when they are ready to be studied in clinical trials.





Mon, Sep 17 3:01pm · CIMCON18 -- How genomics discovery is transforming individualized care and the path forward

This article originally appeared on the Center for Individualized Medicine blog on Sept. 17, 2018.

Article by Sharon Rosen

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.

Thu, Aug 23 8:00am · Using the body to recognize and attack cancer

This article originally appeared in the Center for Individualized Medicine blog on July 23, 2018

For as long as he can remember, Saad Kenderian, M.B., Ch.B., wanted to be a physician. Nothing could blunt his resolve –not even when improvised explosive devices, bombs and trappings of war put the medical school in his native Baghdad, Iraq, on a brief hiatus. It is with that same determination he leads Mayo Clinic’s research into chimeric antigen receptor (CAR) T-cell therapy, which unleashes the immune system to attack cancer.

Saad Kenderian, M.B., Ch.B.

“With CAR T, we are on the verge of discovering the potential of immune cells. The results that we are seeing are truly unprecedented, especially in B-cell leukemias and lymphomas. Some patients who really have no other hope are going into complete remission,” says Dr. Kenderian.

With support from the Mayo Clinic Center for Individualized Medicine, Dr. Kenderian’ s team is investigating ways to expand CAR T-cell therapy beyond blood cancers to solid tumors and to autoimmune diseases like colitis.

Fighting cancer with genetically engineering cells

CAR T-cell therapy seeks to harness the power of the immune system by genetically modifying cells, equipping them with power to kill cancer. These synthetic cells act like a living drug that uses the body’s defense system to fight disease.

“This is a prime example of individualized immune therapy. Immune system T-cells are taken from each patient and engineered with an artificial protein that supercharges them to recognize and attack cancer. A large number of these cells are then injected back into the body. It’s a therapy shaped to each patient,” Dr. Kenderian says.

CAR T-cell therapy may be used on lymphoma and leukemia patients whose cancer has returned twice and no longer responds to standard therapy. Studies are underway to investigate whether it would be beneficial to start CAR T-cell therapy earlier.

One focus of Dr. Kenderian’s research is the “next generation” of CAR T-cell therapy. The research is looking for treatment with fewer side effects, lower cost, and use on solid tumors.

“The first challenge with that is unlike blood cancers, there is no unique protein or marker on the cancer cells for the CAR T-cells to attack. The second challenge is that solid tumors have a unique environment that is able to shut down the CAR T-cells. We hope to advance our understanding about this within the next five years,” he said

Fascinated with the immune system

Part of Dr. Kenderian’s dream was to practice medicine in the United States. After completing his residency at Michigan State University McLaren Hospital, he came to Mayo Clinic for a fellowship in hematology and oncology. It was during that time he grew fascinated with the power of the immune system and the potential that a patient’s body could fight disease.

“Tapping the immune system is perhaps one of the only therapeutic strategies that we can talk about as a potential cure (for cancer),” he says.

As part of his fellowship, Dr. Kenderian studied under the pioneers of CAR T-cell therapy at the University of Pennsylvania. He returned in 2016 to help establish the CAR T therapy program at Mayo Clinic.

Mayo is a leader in CAR T-cell therapy

Mayo Clinic is now one of a select few medical centers in the United States to offer CAR T-cell therapy in a clinical setting.

“Mayo Clinic is unique in this setting, because we have the clinical infrastructure to deliver the CAR T-cell therapy. And we have a solid interdisciplinary collaboration between basic science, clinical sciences and translational approaches to bring these discoveries to the clinic,” he says.

CAR T-cell therapy will be showcased at this year’s Individualizing Medicine Conference.

Sponsored by the Mayo Clinic Center for Individualized Medicine, the conference will be held on Sept. 12-13 at the Mayo Civic Center in Rochester.  You can register to attend here.

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


Thu, Aug 9 6:00am · Using CSI-type technology to unravel the source of bacteria

This article originally appeared on the Center for Individualized Medicine blog on May 28, 2018.

Mayo Clinic laboratory workers have a new tool to perform high tech genetic sleuthing for the source of stubborn, sometimes life-threatening bacteria. Bacterial whole genome sequencing can trace individual isolates of bacteria such as Staphylococcus aureus, also known as Staph aureus, to determine if an outbreak is occurring. This common bacterium that has plagued health care facilities, nursing homes, neonatal intensive care units and sports teams can lead to serious infections and can be resistant to some available antibiotics.

Robin Patel, M.D.

“If we have two or more people infected with the same type of bacterium, the question sometimes arises as to whether they got the organisms from one another or a shared source. The answer to this question can shape an approach to limit further spread,” says Robin Patel, M.D., a clinical microbiologist with Mayo Clinic Department of Laboratory Medicine and Pathology. “Or, a patient might have a bacterial infection and later a second infection with the same type of bacterium. Whole genome sequencing can determine whether the patient picked up a new ‘version’ of the bacterium or if the old one never went away. This can matter for management of that patient.”

Staph aureus bacteria are a leading cause of skin and underlying infections, such as boils, abscesses and cellulitis. Often this type of infection is not serious. However, the same organism-type can cause more serious infections, such as bone or joint infections. Sometimes Staph aureus can spread to the bloodstream and become life threatening.

In the past, getting to the source of outbreaks and transmission was tricky. Prior to bacterial whole genome sequencing, lab workers had to rely on a type of molecular testing, called pulsed-field gel electrophoresis, that was tedious, difficult to analyze and produced only a fraction of the information that DNA sequencing does.

Nicholas Chia, Ph.D.

“It is important to develop tests that can distinguish how individual bacteria are related to one another and to understand and control the spread of bacterial infections,” says Nicholas Chia, Ph.D., assistant director of the Center for Individualized Medicine Microbiome Program.

Mayo Clinic Center for Individualized Medicine is working with the Mayo Clinic Department of Laboratory Medicine and Pathology to bring to the medical practice new testing methods that look at the entire genomes of human pathogenic bacteria.

“With microbial whole genome sequencing, we can discover all there is to possibly know about an organism. It is cutting edge technology that’s a little like CSI (crime scene investigation) in a way. We are providing information to assess relatedness, which will in turn direct interventions to interrupt transmission,” says Dr. Patel.

Research has shown that whole genome sequencing can help track the source of the stubborn superbugs such as methicillin-resistant Staphylococcus aureus, or MRSA, outbreaks that have been reported in high school, college and professional sports teams, in addition to in health care facilities. Many times, MRSA infection is spread via turf, locker room towels or personal contact between athletes. Whole genome sequencing can confirm the presence of an outbreak.

“Examining the entire bacterial genome, we will, in the near future, be able to identify resistance genes and mutations, therefore defining which antibiotics are going to be active. Our early research indicates that we can use whole genome sequencing to inform drug selection and therefore how that patient should be treated. It is so new, we’ve elected to look at this application separately from the strain relatedness testing approach we are currently performing,” says Dr. Patel.

Mayo Clinic is one of the first medical centers in the United States to routinely perform whole genome sequencing of Staph aureus bacteria in its clinical labs. The tests for this and other bacteria are available to other health care facilities through Mayo Medical Laboratories.

Additional research can be found here.

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For more information on the Mayo Clinic Center for Individualized Medicine, and how it is transforming care through the discovery, translation and application of precision medicine research, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Save the date for this year’s Individualizing Medicine Conference. It will be held Sept. 12-13, 2018 in Rochester, Minnesota.

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