The Genomic Medicine Institute (GMI) serves as the expert base for the principles and practice of genomic medicine, including genetics and genomics research, clinical care, and outreach and education directed at genomics-based personalized healthcare. Research conducted at GMI focuses on both translational and clinical human genetics and genomic science, meaning discoveries made in the laboratory will advance the field of precision medicine and, ultimately, improve the quality of patient care.
GMI, founded over a decade ago by Charis Eng, MD, PhD, Chairperson, is specifically designed with open laboratory space in order to enhance genomics research. Researchers work together with clinicians in the clinical arm of the Institute — the Center for Personalized Genetic Healthcare — as well as the Genomic Medicine Biorepository, which processes and stores thousands of patient samples and biological molecules linked to a relational database, and the Genomics Core facility, which utilizes cutting-edge genomics technology for multiple researchers within the Cleveland Clinic and externally.
The Institute offers a unique training program to young investigators who wish to apply genomics to their research or medical practice. GMI also coordinates genomic research and practice across many disease areas to enhance interdisciplinary research and healthcare.
At a special ceremony in Washington, D.C., on October 18, Charis Eng, MD, PhD, was awarded the American Cancer Society’s Medal of Honor, the organization’s highest level of recognition. It was a career-defining moment for the internationally renowned genetics researcher, who says she knew from childhood what she wanted to do in life.
“When I was a young girl playing with my chemistry set and stethoscope, I never imagined this,” says Dr. Eng, Founding Chair of Cleveland Clinic’s Genomic Medicine Institute. She also is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine and Director of Cleveland Clinic’s Center for Personalized Genetic Healthcare.
“I am honored and humbled to receive the American Cancer Society’s Medal of Honor for Clinical Research. To receive it on stage with the Honorable Joseph R. Biden Jr., Dr. Michael J. Thun, as well as Drs. Jennifer Doudna and Emmanuelle Charpentier, the co-discoverers of CRISP-CAS9 gene editing, was overwhelming.”
Dr. Eng notes that her entire career has been devoted to understanding the genes that play a role in heritable cancers and translating those findings into improved patient care. “For example, our research led to the discovery of the relationship between certain germline (occurring in every cell of the body) PTEN mutations and Cowden syndrome, which carries high risks of breast, thyroid and other cancers. These discoveries were rapidly translated into everyday medical practice.”
She continues, “We’ve since discovered other genes, as well, each of them bringing different cancer risks when mutated. Our work has characterized the age at cancer risk and the precise cancer risk associated with each gene over a lifetime, such that doctors can closely watch (enhanced surveillance) those who have gene mutations and catch the cancers early and when curable. Our work has broad implications for diagnosis, prognosis, therapy and prevention, forming the basis for precision oncology practice.”
In her award acceptance speech, Dr. Eng emphasized the importance of collaboration and teamwork through the years. “Like all such honors, it is not to an individual,” she said. “No, it is because of my research and clinical teams, past and present, and, might I say, future. It is because of my colleagues and collaborators. It is because of my mentors. It is equally to my parents, who supported me through thick and thin.”
She also thanked Cleveland Clinic and Serpil Erzurum, MD, Chair of the Lerner Research Institute, for providing “a wonderful work culture” that helped her achieve success. Recounting how the American Cancer Society funded her early in her career, she says, “They gave me a Research Scholar Grant, and so I’m very grateful. Without that grant, I would not be where I am today.”
Dr. Erzurum, who holds the Alfred Lerner Memorial Chair in Innovative Biomedical Research, praises Dr. Eng for significant contributions to her field.
“Charis is a true pioneer in cancer genomics, especially integrating the study of genetics into clinical care,” Dr. Erzurum says. “As a physician-scientist for over 20 years, she has dedicated her career to patient-oriented research in genetics and genomic medicine. She also has an unparalleled passion for mentoring the next generation of physician-scientists, PhDs, clinical researchers and healthcare leaders.”
Dennis Lal, PhD, is an investigator with Cleveland Clinic’s Genomic Medicine Institute. Dr. Lal uses genetic data from in-house and globally collected patient cohorts to discover genes related to epilepsy syndromes, to develop novel methods for interpreting missense variants and to characterize patient disease trajectories. Dr. Lal also has an appointment at Cleveland Clinic’s Epilepsy Center, and is a Visiting Scientists with Investigator status at the Broad Institute of Harvard and the Massachusetts Institute of Technology.
The Lal Research group at Cleveland Clinic studies large-scale genetic and clinical biomarkers from thousands of patients to improve our understanding of brain disorders and aims to subsequently translate the gained knowledge into clinical care.
In 2016, Dr. Lal began a weekly online series on neurodevelopmental disorders accessible freely to all interested individuals. This online journal club is hosted on YouTube, and there are more than 80 presentations available for public viewing, which have been accessed in more than 100 countries across the globe.
Dr. Lal received his BS and PhD from the University of Cologne, Germany, where he served as a group leader in large-scale genetic studies of epilepsies. He then completed a post-doctoral fellowship at the Broad Institute of Harvard and the Massachusetts Institute of Technology, investigating method development for statistical analysis of neurodevelopmental disorders.
David B Flannery, MD, is the Director of Telegenetics and Digital Genetics, as well as a Staff Physician in Cleveland Clinic’s Genomic Medicine Institute. He sees patients on Main Campus and via telegenetics technology.
Dr. Flannery is certified by the American Board of Pediatrics and the American Board of Medical Genetics. Dr. Flannery completed his bachelor’s degree in psychology from Columbia University, and received his medical degree from Emory University. He completed his pediatrics residencies at the Emory University Affiliated Hospitals and the University of Virginia, and his fellowship in human genetics at the Medical College of Virginia. Dr. Flannery also earned a post-graduate certificate in Health Services Research and Health Economics from the Medical College of Georgia. He is board-certified in both Clinical Genetics and Pediatrics.
A physician leader with a national reputation for shaping the policy and practice of medical genetics, Dr. Flannery has been a key figure in driving the adoption of telegenetics solutions. He has also been active internationally, representing the American Academy of Pediatrics on the World Health Organization’s Topic Advisory Group for the development of ICD-11 codes for genetics, as well as on the Pediatric Task Team of the Global Alliance for Genomics and Health. Dr. Flannery also served as an accreditation site visitor for the American Board of Genetic Counseling, and holds leadership positions with the American Medical Association.
Dr. Flannery has nearly 40 years of clinical experience, including appointments at the University of Virginia’s School of Medicine and the Medical College of Georgia at Augusta University, and has published extensively in clinical genetics, telemedicine and dysmorphology, and is a frequent presenter at national meetings. Most recently, Dr. Flannery served as Medical Director of the American College of Medical Genetics and Genomics, the National Coordinating Center for Regional Genetics Collaboratives, and the Newborn Screening Translational Research Network.
His specialty interests include general genetics, pediatric genetics, prenatal genetics, cardiovascular genetics, cancer genetics, telemedicine, and telegenetics.
Pharmacogenomics: An Emerging Clinical Tool
Inter-patient variability in response to medications is an ongoing concern in the medical field. Despite adjustments for age, weight, concomitant medications, and renal or hepatic function, certain patients respond well, some experience severe adverse effects while others do not respond to the same drug therapy. Numerous studies, spanning several decades, have demonstrated that genetic polymorphisms are one of the main factors that influence medication response.
Pharmacogenomics, the study of how an individual’s genetic variations impact the response to drugs, has emerged as an essential tool to optimize therapy and minimize the risk of adverse effects. In general, genetic polymorphisms result in alterations of pharmacokinetic and/or pharmacodynamics properties which are then reflected in therapy outcomes that range from potentially life-threatening adverse effects to inadequate therapeutic response. The goal of pre-emptive pharmacogenomics testing is to take into account the impact of each individual’s genetic variants when selecting therapy thus providing personalized medicine. The benefits of incorporating pharmacogenomics can be exemplified in patients who are diagnosed with major depressive disorder. The majority of patients will need 6 to 12 weeks on a steady antidepressant dose to experience sufficient symptom relief. However, some patients will experience adverse effects or insufficient improvement necessitating changes in therapy and extending the time to remission of symptoms. This results in frustration for the patient along with potential for poor outcomes and higher treatment costs. Pharmacogenomic testing may help identify subsets of the population who carry genetic variants that may alter psychotropic response to specific antidepressants. With this information, clinicians can minimize the need to trial various antidepressants and the time to a positive therapeutic outcome.
Many commercial laboratories offer pharmacogenomics testing but testing is not standardized,
thus results and interpretations may differ between laboratories. This can lead to confusion and can make clinical application of pharmacogenomic results difficult. To address this concern, Molecular Pathology and Pharmacy are collaborating to develop an in-house pharmacogenomics testing process to provide an additional clinical tool to strengthen the ability to provide quality patient care. Until then to assist with testing and interpretation, the Center for Personalized Genetic Healthcare (CPGH), the clinical arm of the Genomic Medicine Institute (GMI), offers a Pharmacogenomic Clinic that welcomes referrals. This clinic is interdisciplinary and currently staffed by our clinical geneticist, Angelika Erwin, MD and our pharmacogenomics clinical specialist, Jennifer Hockings, PharmD, PhD. Although pharmacogenomics has great potential for clinical utility when used accordingly, many third party payers, including Medicare, may only cover testing for certain disease diagnoses and usually after therapy failure. It is important that patients are aware they may have out-of-pocket costs associated with pharmacogenomics testing.
If you have any questions, please contact the pharmacogenomics clinical specialist, Jennifer
Hockings (email@example.com; 216-442-5535).
Charis Eng, MD, PhD, was awarded a computational grant (110,000 resource units) from Ohio Supercomputer Center, Columbus, for a project titled: “Insight into Structure and Dynamics from Computational Modeling and Simulation: The Effects of Germline PTEN Mutations in Autism Spectrum Disorder and Cancer.” The project is aimed at understanding the dynamics and structure of PTEN in Autism Spectrum Disorder (ASD) vs. cancer-associated mutations in context of the lipid membrane as well as its lipid substrate phosphatidylinositol 3,4,5 triphosphate (PIP3) and adenosine triphosphate (ATP). “Understanding the functional impact that ASD- vs. cancer-associated germline PTEN missense mutations have on the structure of PTEN will aid in a better clinical-molecular classification and prediction of associated phenotypes,” says postdoctoral fellow Iris N Smith, PhD, who is working on the project. “This will potentially allow for translation into new diagnostic and therapeutic approaches.
We are thrilled to announce that GMI's Genetic Counselor Brandie Leach, MS, LGC has been elected to the Board of Directors for the Lynch Syndrome Screening Network! The Lynch Syndrome Screening Network promotes universal tumor screening of individuals with newly diagnosed colorectal and endometrial cancers. Its goal is to reduce the cancer burden associated with Lynch syndrome for patients and their families.
CPGH received an enterprise Excellence Award for teamwork, recognizing the team for its commitment to delivering quality patient care when the department was short-staffed. CPGH’s genetic counselors, part-time physicians, and support staff worked around the clock to ensure that patients received comprehensive clinical genetics services based on their levels of acuity. They had a significant impact on both patient care and business operations, even slightly increasing the number of patients served compared to 2016 when the group was fully staffed.
On November 8, 2017, GMI student Lamis Yehia successfully defended her PhD thesis titled, Novel Role of SEC23B as a Cancer Susceptibility Gene in Cowden Syndrome and Apparently Sporadic Thyroid Cancer. Dr. Yehia (!) completed her doctoral studies in the Cancer Biology Training Program within Case Western Reserve University’s Department of Pathology, where she was mentored by GMI Chair Dr. Charis Eng.
In an interview with Cleveland Clinic's Chief of Staff Dr. Brian Donley, Dr. Eng explains why the topic of genomics and precision medicine is so important right now and shares her own story as a patient.
CPGH genetic counselor Allison Schreiber, MS, LGC, discusses genetic testing for patients with autism with long-time GMI friend and Chief Science Officer of Autism Speaks Tom Frazier II, PhD, during his keynote address at MIS2017. (Allison joins Dr. Fraizer at 15:10.)
10/27/17 - Charis Eng, MD, PhD, founding Chair of Cleveland Clinic’s Genomic Medicine Institute and founding Director of the institute’s clinical component, the Center for Personalized Genetic Healthcare, was honored with a Professional Achievement Award from the University of Chicago Alumni Association. Click here for the full press release.
10/26/17 - More than 2,500 people gathered in downtown Cleveland on October 23-25 for the 15th annual Medical Innovation Summit hosted by Cleveland Clinic Innovations. This year’s theme was Genomics & Precision Medicine. GMI played a major role in planning the event, and GMI Chair Charis Eng, MD, PhD, spoke on multiple panels. Memorably, Dr. Eng shared her own cancer journey in a conversation with Cleveland Clinic’s Chief of Staff, Brian Donley, MD, to open the Summit.
Pictured above from left to right: Sirena Meade, Dr. Charis Eng, Lamis Yehia, Dr. Sara Akhavanfard
Dr. Eng participated in the following panel discussions:
Pictured above from left to right: Meg Tirrell, Cindy Collins, Christine Cournoyer, Dr. Charis Eng, Alexander Ford.
Wednesday’s keynote speaker was long-time GMI colleague Tom Frazier, PhD, Chief Scientific Officer of Autism Speaks. As part of his keynote address, Dr. Frazier interviewed GMI genetic counselor Allison Schreiber, MS, LGC, who played an important role in helping to identify a genetic component of his son’s autism diagnosis.
Pictured above: Dr. Tom Frazier and Allison Schreiber
Thanks to Cleveland Clinic Innovations and all who worked to make this summit a successful learning and networking opportunity!
10/6/17 - Charis Eng, MD, PhD, along with co-senior author Stephen Grobmyer, MD, uncovered differences in the bacterial composition of breast tissue in healthy women compared to that of women with breast cancer. The findings were recently published in the journal Oncotarget. According to Dr. Eng, this study of the breast tissue, oral and urinary microbiomes in breast cancer is the first to examine both breast tissue and distant sites for bacterial differences in breast cancer.
“Our hope,” said Dr. Eng, “is to find a biomarker that would help us diagnose breast cancer quickly and easily. In our wildest dreams, we hope we can use microbiomics right before breast cancer forms, and then prevent cancer with probiotics or antibiotics.”
Breast cancer is the second most common cancer in women (after skin cancer) in the United States, where 1 in 8 women will develop the disease in their lifetimes.
To read the full press release, click here.
9/29/17 - The Genomic Medicine Institute’s (GMI) 5th annual Genetics Education Symposium entitled, “Genetics & Genomics: A Focus on Women’s Health” was held on Thursday, September 9th at the InterContinental Hotel and Conference Center in Cleveland, Ohio. This day-long symposium was attended by more than 200 healthcare professionals and students from a variety of organizations.
The presentations focused on advances in the diagnosis, management, and treatment of genetic conditions in diseases affecting women. Presentations included: Genetics Primer & Clinical Updates by Linford Williams, MS, LGC; Genetics and Women’s Health: Seeing and Foreseeing the Ethical Challenges Ahead by Ruth Farrell, MD, MA; Preimplantation Genetic Screening and Diagnosis: What You Need to Know by Marissa Coleridge, MS, LGC; Evolution of Prenatal Genetic Screening and Testing: NIPT and Beyond by Jeff Chapa, MD, MBA; Promises and Pitfalls of Prenatal Whole Exome Sequencing by Amanda Kalan, MD; Fertility Preservation and Cancer: Survivors, Previvors, and the Newly Diagnosed by Rebecca Flyckt, MD; Improving Access to Cancer Genetics via Telegenetics by Ryan Noss, MS, LGC; Breast Cancer: Management of Moderate Penetrance Predisposition Genes by Holly Pederson, MD; Use of Hormonal and Non-hormonal Therapies in Breast Cancer Survivors and Women at High Risk for Breast/Gyn Cancers by Holly Thacker, MD; Addressing Commonly Asked Patient Questions about Genetics by Rebekah Moore, MS, LGC, Christina Rigelsky, MS, LGC and Allison Schreiber, MS, LGC; and a panel discussion on Genetic Testing Reimbursement featuring Bruce Rogen, MD, MPH and John Yao, MD, MBA, MPH, which was moderated by Daniel Sullivan, MD. Charis Eng, MD, PhD, course director, founding Chair of the GMI and Director of the Center for Personalized Genetic Healthcare, concluded the day with her presentation Your Genes, Your Wine, Your Health, followed by a wine reception.
Pictured above from left to right: Dr. Daniel Sullivan, Dr. Bruce Rogen, Dr. John Yao
Pictured above: Marissa Coleridge
This year’s symposium also showcased GMI trainees who gave “lightning talks,” or quick summaries, of GMI research and poster presentations displayed throughout the day.
Keep updated on all GMI events, seminars, and next year’s symposium by subscribing to our newsletter. To subscribe, email Jenn Lonzer, GMI’s Communication and Education Coordinator at firstname.lastname@example.org.
Pictured above from left to right: Dr. Holly Pederson, Dr. Holly Thacker, Dr. Charis Eng
4/21/17 - Charis Eng, MD, PhD and her research team including first author Ying Ni, PhD, postdoctoral fellow, at the Cleveland Clinic’s Genomic Medicine Institute have discovered that a faulty, rarely studied gene called USF3 may predispose individuals to thyroid cancer.This exciting research was recently published in Human Molecular Genetics.
The discovery of this cancer predisposition gene will facilitate predictive genetic testing, risk assessment, genetic counseling and clinical management of the disease.
Featured in over 13 media outlets, including:
American Association for the Advancement of Science - EurekAlert
Cleveland Clinic - ConsultQD
Full journal publication here:
Human Molecular Genetics
1/19/17 - Since her discovery of the PTEN gene in 1997, cancer geneticist and Cleveland Clinic Genomic Medicine Institute Chair, Charis Eng, MD, PhD has collaborated with physicians and scientists across the nation to determine the impact of a PTEN gene mutation. Their research determined that this gene, in some cases, can cause both cancer and autism. This subtype of autism has been named PTEN-ASD and is estimated to affect up to 2% of individuals with autism.
That was the story of a boy in Tulsa, Oklahoma, Charlie Ryan, one of Dr. Eng’s patients at Cleveland Clinic’s Center for Personalized Genetic Healthcare. After her son developed autism and a benign tumor - Charlie’s mother was determined to find out what could cause such seemingly polar diseases. Her research led Charlie to Cleveland Clinic to be treated by Dr. Eng and autism expert, Thomas Frazier, PhD. In a story by Spectrum, an autism news site, Charlie’s parents tell their story. The article also includes how PTEN was discovered, the impact of a PTEN gene mutation, and finally, the treatment options for Charlie and others like him. Read the whole story on Spectrum’s website here.