Charis Eng, MD, PhD

Professor and Vice Chair
Department of Genetics and Genome Sciences
School of Medicine
Department of Molecular Medicine
School of Medicine
Cancer Genomics and Epigenomics Program
Case Comprehensive Cancer Center

Charis Eng, MD, PhD is the Chair and founding Director of the Genomic Medicine Institute of the Cleveland Clinic, founding Director and attending clinical cancer geneticist of the institute's clinical component, the Center for Personalized Genetic Healthcare, and Professor and Vice Chairman of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine. She holds a joint appointment as Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine and is a member of Cleveland Clinic's Taussig Cancer Center and of the CASE Comprehensive Cancer Center. Dr. Eng was honored with the Sondra J. and Stephen R. Hardis Endowed Chair in Cancer Genomic Medicine in 2008 and the American Cancer Society Clinical Research Professorship in 2009. In 2010, she was elected to the National Academy of Medicine [then Institute of Medicine (IOM)] of the US National Academies. She continues to hold an honorary appointment at the University of Cambridge. Dr. Eng's research interests may be broadly characterized as clinical cancer genetics translational research. Her work on RET testing in multiple endocrine neoplasia type 2 and characterization of the widening clinical spectra of PTEN mutations have been acknowledged as the paradigm for the practice of clinical cancer genetics, and an important scientific basis for precision oncology. At the clinical interface, Dr. Eng is acknowledged as one of the rare "go to" people on what is and how to implement genetic- and -omics-informed personalized healthcare.

Dr. Eng grew up in Singapore and Bristol, UK and entered the University of Chicago at the age of 16. After completing an MD and PhD at its Pritzker School of Medicine, she specialized in internal medicine at Beth Israel Hospital, Boston and trained in medical oncology at Harvard's Dana-Farber Cancer Institute. She was formally trained in clinical cancer genetics at the University of Cambridge and the Royal Marsden NHS Trust, UK, and in laboratory-based human cancer genetics by Prof Sir Bruce Ponder. At the end of 1995, Dr. Eng returned to the Farber as Assistant Professor of Medicine, and in January, 1999 was recruited by The Ohio State University as Associate Professor of Medicine and Director of the Clinical Cancer Genetics Program. In 2001, she was honored with the conferment of the Davis Professorship and appointed Co-Director of the Division of Human Genetics in the Department of Internal Medicine. In 2002, she was promoted to Professor and Division Director, and was conferred the Klotz Endowed Chair. She was recruited to the Cleveland Clinic in Sept, 2005. Dr. Eng has published over 470 peer reviewed original papers in such journals as the New England Journal of Medicine, JAMA, Lancet, Nature Genetics, Nature, Cell and Molecular Cell. She has received numerous awards and honors including election to the American Society of Clinical Investigation, to the Association of American Physicians and as Fellow of AAAS, the Doris Duke Distinguished Clinical Scientist Award, and named a Local Legend from Ohio bestowed by the American Medical Women's Association in conjunction with the US Senate on women physicians who have demonstrated commitment, originality, innovation and/or creativity in their fields of medicine. Dr. Eng is the 2005 recipient of the ATA Van Meter Award at the 13th International Thyroid Conference, the 2006 Ernst Oppenheimer Award of The Endocrine Society, the 2006 American Cancer Society John Peter Minton, MD, PhD Hero of Hope Research Medal of Honor, the 2014 James Ewing Lecturership of the Society for Surgical Oncology, the 2014 AACR WICR-Charlotte Friend Memorial Lectureship, 2015 and 2017 University of Chicago Medical Alumni Distinguished Service Award and Alumni Professional Achievement Award. She serves as the Editor-in-Chief of Endocrine Related Cancer (2011-2020). She was the North American Editor of the Journal of Medical Genetics (1998-2005), Senior Editor of Cancer Research (2004-09), and Associate Editor of the Journal of Clinical Endocrinology and Metabolism (2005-09) and of the American Journal of Human Genetics (2007-09). Dr. Eng completed a 3-year term on the Board of Directors of the American Society of Human Genetics, has completed a 2-year term as Chair of the Clinical Science Committee of the Personalized Medicine Coalition and a 5-year term on the Board of Scientific Directors of the National Human Genome Research Institute. Dr. Eng was appointed by Kathleen Sebelius to the US Department of Health and Human Services' Secretary's Advisory Committee on Genetics, Health and Society (2009-11). She also served as co-chair of their Task Force to examine whole genome sequencing for clinical application.

Research Information

Research Interests

We use multidisciplinary approaches to identify and characterize genes which cause susceptibility to inherited cancer syndromes, to determine their role in sporadic carcinogenesis and to perform molecular epidemiologic analyses as they relate to clinical applications. Upon this framework, we are using PTEN hamartoma tumor syndrome (PHTS) as our model. PHTS is defined as any individual carrying germline PTEN mutations, irrespective of clinical diagnosis (eg, no phenotype, Cowden syndrome, BRRS, etc). PHTS is an autosomal dominant disorder characterized by a high risk of breast, thyroid, endometrial, renal and colon cancers, and the seemingly unrelated autism spectrum disorder (ASD). Interestingly, PTEN is now considered among the most common monogenic causes of ASD. Our focus is to take a multidisciplinary approach, namely, genomic modifiers, metabolomic, structural/proteomic, microbiomic, immune, etc, to get at the question of who amongst those with PHTS will develop cancer versus ASD, both or no signs at all. Hence, we are looking for gene-gene interactions and gene-en(in)vironment interactions that will result in these seemingly dichotomous phenotypes. In searching for dichotomizing modifiers, we also seek to understand non-traditional mechanisms of PTEN inactivation in this context. For example, we are utilizing murine models and iPSC models to interrogate such non-canonical loss-of-function as an aetiology of PTEN-ASD, chief of which involves nuclear-cytoplasmic trafficking., This fundamental research is aimed at not only mechanism resolution but also hopes to identify novel targets for therapy and prevention. As such, we continue to enroll and follow our large cohort of persons with PHTS and to analyze cancer risks in a longitudinal manner. We first characterized cancer risks in PHTS in 2012 and it is this week that has seeded national practice guidelines for high risk management of these persons. We have just completed a re-analysis after another 10 years of cancer risks in PHTS individuals.

Research Projects

The major focus of my lab is to dissect the PTEN "Switch" of developing cancer versus ASD: Why and how germline mutation in a single gene PTEN results in such disparate phenotypes as cancer and autism remains a conundrum. A major thrust of my lab is to determine the mechanistic "switch(s)" which differentiates the two clinical outcomes. Because of the complexity of our overall goal, we are pursuing an in parallel multidisciplinary approach. One important group of projects are utilizing genomic (WGS based), transcriptomic and metabolomic (singly and integratively) approaches leveraging our collection of well-phenotyped and annotated patient materials. Another set of projects utilizes iPSC cells with engineered patient PTEN mutations in proximity but with cancer and ASD, respectively. By differentiating them into the relevant organoids (brain versus eg thyroid for thyroid cancer), characterization and functional interrogation should yield the mechanism for dichotomizing the cancer vs ASD phenotypes.

In order to understand the PTEN "switch," it is important to characterize our Pten mouse model of inappropriate Pten subcellular localization, and with autism-like phenotypes. One model is a first mouse model of inappropriate Pten cytoplasmic predominance with high-functioning autism as phenotype. We subsequently made a nuclear predominant Pten, and are comparing the two models at the cellular and organismal levels. So far, we have shown for the first time a major role of microglia in the genesis of autism-like behaviors in these mice.

Another project looks at whether microbiome differences could be responsible for cancer vs ASD outcomes in PHTS patients. The microbiome comprises microbial organisms, such as bacteria and fungi, that are found in and on human bodies. Emerging data have shown the microbiome affecting obesity, diabetes and inflammatory bowel disease as well as responses to immune modulation in cancer treatment. This project therefore addresses our overarching hypothesis that the microbiome transduces signals from the environment to our genes. We are studying the microbiome from gut, urine and oral wash as a modifier of cancer and ASD risk in individuals with PHTS, and in those with and without PHTS. In parallel, we are analyzing the microbiome from tumor and non-tumor tissue as well as gut in sporadic solid tumors that are component to PHTS, namely, breast and thyroid cancers.

External Appointments

Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine
Cleveland Clinic
Lerner Eminent Scholar and Director of Global Genomics Research Strategy
Cleveland Clinic
Chairwoman, Genomic Medicine Institute
Lerner Research Institute, Cleveland Clinic
Chairwoman, Center for Personalized Genetic Healthcare
Medical Specialties Institute, Cleveland Clinic

Additional Information