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Charis Eng, MD, PhD, FACP: Leading the Way in Genomic Medicine




Dr. Charis Eng knew that she wanted to spend her working life in two places — the research bench and the patient bedside — even before the term “translational 
medicine” existed.

“I knew that I wanted to be a doctor from the time I got my first chemistry set at the age of four,” says the Singapore-born chair and founding director of Cleveland Clinic’s Genomic Medicine Institute. “But I also knew that I wanted to be a scientist or more specifically a physician-scientist. When I came to the U.S., I realized you could do both.”

Today, Dr. Eng is one of only four formally trained clinical cancer geneticists in the country and has produced paradigm-shifting research that has changed the understanding of cancer. She has published more than 330 peer reviewed original papers in such journals as The New England Journal of Medicine, JAMA, The Lancet, Nature Genetics, Nature, Cell and Molecular Cell.

Since joining Cleveland Clinic in 2005, the woman whose research was once considered too “out there” to obtain NIH funding, has won more than 70 research grants and awards totaling over 
$20 million for her cutting edge studies of human cancer genomics, the complex interactions between genes and their impact on disease. She is a tenured professor and vice chair of the Department of Genetics at Case Western Reserve University School of Medicine, professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine, and the Sondra J. and Stephen R. Hardis Endowed Chair in Cancer Genomic Medicine at Cleveland Clinic.

In addition to being a scientist, 
Dr. Eng is also living her dream of being an active clinician and directing a team of clinically trained genetic counselors as founding director of The Center for Personalized Genetic Healthcare, the Genomic Medicine Institute’s clinical arm. As medical director of Cancer Genetics Services as well, she practices and leads what she has been uniquely trained in — clinical cancer genetics.

“I always tell my patients that genetic knowledge is power,” she says. “It is not about good news or bad news; it is about understanding the underlying cause of disease and using it to tailor a roadmap of prevention.”

Dr. Eng’s high impact patient-oriented cancer research and her skill as a mentor earned her an appointment as American Cancer Society Clinical Research Professor in 2009, a distinction held by only 15 clinical researchers at any one time. That same year, she was appointed to the U.S. Health and Human Services’ Secretary’s Advisory Committee on Genetics, Health and Society, and in 2010 she became one of 65 new members elected to the Institute of Medicine of the U.S. National Academies.

Among Dr. Eng’s other accomplishments are election to the American Society of Clinical Investigation and the Association of American Physicians, winning the Doris Duke Distinguished Clinical Scientist Award, and being recognized as a ‘Local Legend from Ohio’ by the American Medical Women’s Association.

A Serendipitous Childhood

Although she has worked hard for her many achievements, Dr. Eng cites many examples of what she calls ‘serendipity’ in her early years. Born and raised in Singapore, Dr. Eng was inspired by her three prominent uncles, including one who was professor of Medicine and personal physician to the Prime Minister. When she was in 7th grade, her family moved to Chicago where her father pursued a PhD in education. An only child, Dr. Eng was enrolled in the University of Chicago’s renowned Laboratory School where her dreams of being a physician scientist began to take shape.

“Our Advanced Biology teacher at the Lab School ... was very interested in genetics and thus infected us with the genetics ‘bug’,” Dr. Eng wrote in a 2005 profile article for Cancer Biology & Therapy. “In his off hours, he (the teacher) studied cancer education. These were the seeds which sparked my own quest to put genetics and cancer together, well before it was fashionable to do so.”

Serendipity struck again when 
Dr. Eng was just 16. Her father completed his PhD and was required to return to Singapore, but she did not want to leave her studies. Although she could not stay at the Lab School without her parents, 
Dr. Eng’s academic success made it possible for her to gain early admission to the University of Chicago and remain in the U.S., despite her status as a minor. That decision brought her in contact with 
Dr. Ed Garber, a plant fungal geneticist who became her lifelong mentor.

After completing her MD and PhD at the University of Chicago’s Pritzker School of Medicine, she studied internal medicine at Beth Israel Hospital in Boston and oncology at Harvard’s Dana-Farber Cancer Institute. “I moved to Boston because I did not want to be too parochial,” she says.

Once again serendipity came in to play when a fellowship opportunity arose in the emerging field of cancer genetics in Cambridge, England. For three years she was engaged in both clinical practice and research before returning to Dana-Farber Cancer Institute as an assistant professor of Medicine. In 1999, she was recruited by Ohio State University where she became professor and director of the Division of Human Genetics. Six years later, she joined Cleveland Clinic.

A Global Approach to Genomics

Dr. Eng founded and directs the Genomic Medicine Institute as a single platform for research, academic clinical activities, and education in genomic medicine as it enables healthcare. She defines genomics as the study of the entire genetic environment, including the interplay and communication between the 30,000 genes in a human cell and their influence on susceptibility to cancer and other diseases.

“A human is not just one gene. You have to look at the whole environment,” says Dr. Eng. “Genomic medicine should take into account the sum total of gene-gene interactions and gene-environment interactions.”

Dr. Eng has identified four of the ten genes that raise the risk of breast cancer. She and her team are currently working to identify and characterize the genes that cause two heritable cancer syndromes: Cowden syndrome which increases the risk of breast, thyroid and endometrial cancers, and multiple endocrine neoplasia type 2 (MEN 2) which is characterized in part by medullary thyroid cancer and pheochromocytoma (cancer in the adrenal gland). Her discovery of the RET genotype for MEN2 has led to a test for the gene that is now considered to be standard practice. In co-leading an ongoing multinational study, Dr. Eng and her team have also recently determined that 25% of sporadic pheochromocytoma cases are caused by mutations on one of four genes.

Known as “Queen of Cowden,” Dr. Eng found a second significant cancer predisposition gene for Cowden syndrome which was previously known only to be associated with master gene PTEN. Publishing last winter in JAMA, the Eng lab found that epimutation in KLLN which lies next to PTEN also predisposes to multiple cancers and to a higher degree than PTEN. This summer, the Eng laboratory at Cleveland Clinic published in JAMA its finding on the genetic mutation underlying Barrett’s esophagus and/or the cancer esophageal adenocarcinoma. Additional research studies on the role of genomics in sporadic breast and prostate carcinomas and head and neck cancers are ongoing.

“So, our work may have broad implications not only for examining the pathogenesis of common cancers, but may reveal novel targets and novel compartments germane for diagnosis, prognosis, therapy and prevention,” Dr. Eng has written of her research. Indeed, she is proud to say her work on the genes predisposing to Cowden syndrome and to various endocrine cancers have rapidly been translated into practice and codified in professional practice guidelines as useful molecular diagnostic and risk assessment tools to personalize genetic counseling and risk management.

From Bench to Bedside

As a translational researcher, Dr. Eng believes the greatest value for research is in its application in human patients. (“I don’t care about mice,” she quips.) She has worked to integrate genetic services and genetic counselors throughout the Cleveland Clinic system.

In fact, genetic counselors now serve in approximately 20 clinical locations associated with 9 different specialties both on and off the main campus. Last year, 3,000 outpatients saw genetic counselors and geneticists, up from 600 in past years.

“Cleveland Clinic serves 3.8 million people a year. In the past, it could take many months for a patient to get genetic services. We are turning that around by standardizing the practice of genetic testing and counseling and embedding genetic clinical services into non-genetic clinics,” Dr. Eng explains. Her ultimate goal is to streamline and integrate genomic medicine processes into every clinical subspecialty in Cleveland Clinic.

Towards that goal, in early 2008 Dr. Eng began to work on a web-based patient-entered tool that would be compatible with electronic medical records. It included a series of point-of-care clinical decision-support tools including one focusing on family history taking (called MyFamilyHealthHistory) for interrogating risk of cancers and the PTEN Cleveland Clinic Score Risk Calculator. Because of the successful utilization of these tools, Cleveland Clinic is funding a scalable family health history software program for the whole enterprise.

As the field of genomics plays a growing role in clinical practice, at Cleveland Clinic and beyond, more physician scientists are needed. To meet the demand, Dr. Eng founded and directs the Cancer Genomic Medicine Fellowship Training Program at Cleveland Clinic’s Genomic Medicine Institute. Her goal is to bring top minds into a field that she believes represents the future of healthcare.

“Right now, most clinicians practice by the law of averages,” she explains. “We prescribe drugs and see that 15 percent of people respond to it, but what about the other 85 percent? Genomic medicine will allow us to personalize the choice of medications as well.”

Dr. Eng says she is proud to have led Cleveland Clinic into this new era, and she looks forward to a future in which translational researchers, who are also physicians like her, will play an increasingly critical role.

“Anyone can do research,” she says. “But we need translational investigators to translate that into something meaningful for the patient.”

 


 

MD News November/December 2011, Cleveland/Akron/Canton


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