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Andrew Paul Feinberg, M.D., M.P.H.
King Fahd Professor of Medicine, Oncology, Molecular Biology & Genetics, School of Medicine
Professor of Medicine
Languages: English, French
Expertise: Internal Medicine
Research Interests: Epigenetics in development and disease
Andrew Feinberg studied mathematics and humanities at Yale in the Directed Studies honors program, and he received his B.A. (1973) and M.D. (1976) from the accelerated medical program at Johns Hopkins University, as well as an M.P.H. from Johns Hopkins (1981).
He performed a postdoctoral fellowship in developmental biology at UCSD, clinical training in medicine at University of Pennsylvania, and genetics research and clinical training at Johns Hopkins.
Dr. Feinberg discovered epigenetic alterations in human cancer with Bert Vogelstein in 1983.
He was a Howard Hughes investigator at University of Michigan from 1986-1994, when he returned to Johns Hopkins as King Fahd Professor of Molecular Medicine in the Department of Medicine.
His work includes the discovery of human imprinted genes, loss of imprinting (LOI) in cancer, and the molecular basis of Beckwith Wiedemann syndrome (BWS), the paradigm of epigenetic cancer syndromes. His discovery of epigenetically altered progenitor cells has led to a paradigm shift in our understanding of carcinogenesis. More recently, he has pioneered studies of the epigenetic basis of disease generally, establishing the first epigenome center in the U.S. He is Director of the Center for Epigenetics in the Institute of Basic Biomedical Sciences at Johns Hopkins, King Fahd Professor of Medicine, Molecular Biology & Genetics and Oncology, as well as Biostatistics in the Bloomberg School of Public Health, member of the Johns Hopkins Kimmel Cancer Center, and he holds an Adjunct Professorship at the Karolinska Institute in Sweden.
His honors include election to the American Society for Clinical Investigation, the Association of American Physicians, the Institute of Medicine of the National Academy of Sciences, and the American Academy of Arts and Sciences, as well as membership on the ISI most cited authors list, a MERIT Award of the National Cancer Institute, a Doctor of Philosophy (Hon. Caus.) from Uppsala University, the President's Diversity Recognition Award of Johns Hopkins University, a Doctor of Philosophy (Hon. Caus.) from the Karolinska Institute, an Inaugural Gilman Scholar of Johns Hopkins University, and the Feodor Lynen Medal.
- King Fahd Professor of Medicine, Oncology, Molecular Biology & Genetics, School of Medicine
- Chief, Division of Molecular Medicine, Department of Medicine
- Director, Center for Epigenetics
- Gilman Scholar, Johns Hopkins University
- Professor of Medicine
- Joint Appointment in Molecular Biology and Genetics
- Joint Appointment in Psychiatry and Behavioral Sciences
- Professor of Oncology
Departments / Divisions
- MD, Johns Hopkins University School of Medicine (1976)
- Johns Hopkins University School of Medicine (1979)
- American Board of Internal Medicine / Internal Medicine (1984)
- American Board of Medical Genetics and Genomics / Clinical Genetics / MD (1987)
B.A., Johns Hopkins University
M.D., Johns Hopkins University, 1976
M.P.H., Johns Hopkins University, 1981
Residency, Johns Hopkins University School of Medicine (Baltimore MD ) (1976)
Research & Publications
Our laboratory is studying the epigenetic basis of normal development and disease, including cancer, aging, and neuropsychiatric illness. Early work from our group involved the discovery of altered DNA methylation in cancer, as well as common epigenetic (methylation and imprinting) variants in the population that may be responsible for a significant population-attributable risk of cancer. Over the last few years, our laboratory has pioneered the field of epigenomics, i.e. epigenetics at a genome-scale level, founding the first NIH-supported NIH epigenome center in the country, and developing many novel tools for molecular and statistical analysis. Several discoveries and avenues of research have arisen from our epigenome center: CpG islands "shores," that drive many of the gene expression differences that distinguish normal tissues from each other and from cancer; the first map of the methylome in normal hematopoietic development, as well as in induced pluripotent stem cell (iPSC) reprogramming, discovering that iPSC retain an epigenetic memory of their cell of origin. We are now determining the epigenetic limitations of complete reprogramming to an ES-cell like state, and how to circumvent these limitations. A major focus is on a chromatin-related finding that much of the genome is organized into large heterochromatin regions with specific posttranslational modifications of histones, extending to 1 megabase or more, and associated with the nuclear lamina. These "LOCKs", for Large Organized Chromatin K (lysine) modifications, expand during differentiation from stem cells. A huge surprise is that these LOCKs also correspond to large domains of hypomethylation that may characterize all cancers and lead to hypervariable gene expression. We are testing the idea that regulation of LOCKs helps mediate normal development and is disrupted in cancer. For example, dimethylation of H3K9Me2 appears necessary for epithelial-mesenchymal transition, a key step in stem cell development, differentiation, response to injury, and cancer invasion. Translational epigenetic projects include the first comprehensive study of the newborn epigenome, and its relationship to the genotype of the child and the parents, prenatal exposure to nutritional requirements such as folate, as well as toxins, and the outcome of epigenetic change in children at familial risk of autism. Another project addresses schizophrenia, a common, profoundly disabling disorder that is already subject of intensive genetic studies. Here we are applying novel tools developed in our epigenome center, to understand the epigenetic contribution in a large case-control study, and to relate epigenetic changes to underlying genetic variation, and to identify any heritable epigenetic change. We are also pursuing a novel model of genetically driven stochastic epigenetic plasticity in evolution and development, which may help to explain Lamarckian-like inheritance, reconciling epigenetics with Darwinism. Using the honeybee as a model to test these ideas, he has uncovered the first evidence for methylation-mediated reversible behavior in a whole organism, the honeybee. This same model has led to the recent discovery of genetic variants increasing methylation variability in autoimmune disease, which helps to explain the relationship between genetics, epigenetics, the environment and disease.
Selected PublicationsView all on Pubmed
Feinberg AP, Irizarry RA, Fradin D, Aryee MJ, Murakami P, Aspelund T, Eiriksdottir G, Harris TB, Launer L, Gudnason V, Fallin MD. Personalized epigenomic signatures that are stable over time and covary with body mass index. Science Translational Medicine 15:49ra67, 2010.
Ji H, Ehrlich LIR, Seita J, Murakami P, Doi A, Lindau P, Lee H, Aryee MJ, Kim K, Rossi DJ, Inlay MA, Serwold T, Karsunky H, Ho L, Daley GQ, Weissman IL, Feinberg AP. A comprehensive methylome map of lineage commitment from hematopoietic progenitors. Nature 467:285-290, 2010.
Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, Daley GQ. Epigenetic memory in induced pluripotent stem cells. Nature 467:338-342, 2010.
McDonald OG, Wu H, Timp W, Doi A, Feinberg AP. Genome-scale epigenetic reprogramming during epithelial to mesenchymal transition. Nature Structural & Molecular Biology 18:867-874, 2011.
Hansen, KD Timp W, Corrada Bravo H, Sabunciyan S, Langmead B, McDonald OG, Wen B, Wu H, Liu Y, Diep D, Briem E, Zhang K, Irizarry RA, Feinberg AP. Increased variation in epigenetic domains across cancer types. Nature Genetics 43:768-775, 2011.
Herb B, Wolschin F, Aryee M, Langmead B, Amdam G, Feinberg AP. Reversible switching between epigenetic states in honeybee behavioral subcasts. Nature Neuroscience 15:1371-1373, 2012.
Liu Y, Aryee JM, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, Reinius L, Acevedo N, Taub M, Ronninger M, Shchetynsky K, Scheynius A, Kere J, Alfredsson L, Klareskog L, Ekstrom TJ, Feinberg AP. Epigenome-wide association data implicates DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nature Biotechnology 31:142-147, 2013.
Academic Affiliations & Courses
Graduate Program AffiliationPreceptor, Predoctoral Training Program in Human Genetics Preceptor, Predoctoral Program in Cellular and Molecular Medicine Preceptor, Predoctoral Program in Biochemistry, Cellular and Molecular Biology Director, BCMB Course in Epigenetics
Activities & Honors
- Elected Fellow, American Academy of Arts and Sciences, 2009
- Elected Fellow, American Association for the Advancement of Science, 2011
- Elected Member, Institute of Medicine of the National Academy of Sciences, 2007
- General Honors, Johns Hopkins University, 1973
- President's Diversity Recognition Award, Johns Hopkins University, 2007
- Doctor of Medicine (Honoris Causa), Karolinska Institutet, 2010
- ISI, Most Cited Authors List (Top 0.1%), 2001
- MERIT Award, National Cancer Institute, 2001
- Delta Omega, National Public Health Honorary Society, 1981
- Jacob and Marcus Wallenberg Fellow, Royal Swedish Academy of Sciences, 2009
- Baruch Spinoza Chair, University of Amsterdam, 2012 - 2013
- Doctor of Philosophy (Honoris Causa), Uppsala University, 2007
- Research Award, Johns Hopkins Medical Society, 1976
- Award for Postdoctoral Investigation, Johns Hopkins University School of Medicine, 1983
- John A. and George L. Hartford Fellowship, 1984 - 1986
- American Society for Clinical Investigation, 1990
- Association of American Physicians, 1995
- Feodor Lynen Medal, 2011
- Inaugural Daniel Coit Gilman Scholar of Johns Hopkins University, 2011
- NIH Director's Pioneer Award, 2011
- Associate Editor, Cancer Research, 1996
- Associate Editor, American Journal of Human Genetics, 1997
- Co-Chair, NCI Workshop on Defining the Epigenome, 2005
- Co-Chair, Keystone Symposium on Cancer Genomics and Epigenomics, 2007
- Co-Chair, Wellcome Trust Symposia on Epigenomics of Common Human Disease, 2010
- College of CSR Reviewers (senior trans-NIH grant review board), NIH, 2009
- Editorial Board, Cancer Cell, 2005
- Editorial Board, Genome Research, 2005
- Grants Review Working Group, California Institute for Regenerative Medicine, 2005
- Editorial Board, Epigenetics and Chromatin, 2008
- Charter Member, NIH Pathology B Study Section, 1993
- Charter Member, NIH Cancer Genetics Study Section, 2003
Videos & Media
Dr. Feinberg on epigenetics and epigenetic maps.