King Fahd Professor of Molecular Medicine,
BA, The Johns Hopkins University, 1973
Our laboratory is studying the epigenetic basis of disease, including cancer, autism, and psychiatric illness. Epigenetics involves changes in DNA and chromatin structure that are remembered by the cell when it divides, such as DNA methylation, genomic imprinting, and histone modification. Epigenetics is important because many of the differences between a germ cell and a somatic cell, or two different tissue types, or a cancer and a normal cell, involve epigenetic changes rather than mutation in the DNA sequence. Early work from our group involved the discovery of specific alterations in 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. This has led to a major cancer epigenetics translational study to introduce epigenetic testing for cancer risk into the general medical setting. We are also investigating the molecular basis of Beckwith Wiedemann syndrome (BWS), the paradigm of cancer-predisposing disorders caused by an epigenetic mechanism, uncovering the first antisense RNA associated with human disease. In addition, we found that BWS is linked to in vitro fertilization technology. Recently we have developed a mouse model of loss of imprinting in cancer, in which we have found that epigenetic alterations in stem cells increase the risk of malignancy, and suggest an epigenetic progenitor origin of human cancer.We are also pioneering genome-wide technolgy for epigenetics research. We have been awarded a Center of Excellence in Genome Sciences (CEGS) from the NIH, to develop novel tools for genome-wide epigenetic analysis, applicable to disease generally. Work in the CEGS is an interdisciplinary collaboration involving investigators in the Schools of Medicine and Public Health, as well as the Icelandic Heart Association. We are applying these tools to common diseases, including bipolar disorder and autism. We are developing tools to investigate methylation, allele-specific gene expression, and chromatin modification genome-wide, and we are developing new quantitative tools for epigenome analysis.
Feinberg AP. Methylation meets genomics. Nature Genet 27:9-10, 2001.
DeBaun MR, Niemitz EL, McNeil ED, Brandenburg SA, Lee MP, and Feinberg AP. Epigenetic alterations of H19 and LIT1 distinguish Beckwith Wiedemann syndrome with cancer and birth defects. Am J Hum Genet, 70:604-611, 2002.
Strichman-Almashanu LZ, Lee RS, Onyango PO, Perlman E, Folke F, Frieman MB, and Feinberg AP. A genome-wide screen for normally methylated human CpG islands that can identify novel imprinted genes. Genome Res, 12:543-554, 2002.
Onyango P, Jiang S, Uejima H, Shamblott MJ, Gearhart JD, Cui H, and Feinberg AP. Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages. Proc Natl Acad Sci USA, 99:10599-10604, 2002.
DeBaun MR, Niemitz EL, and Feinberg AP. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19, Am J Hum Genet, 72:156-160, 2003.
Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Powe NR, and Feinberg AP. Loss of IGF2 imprinting: A potential marker of colorectal cancer risk. Science, 299:1753-1755, 2003.
Feinberg AP and Tycko B. The history of human cancer epigenetics. Nature Reviews Cancer, 4:143-152, 2004.
Bjornsson H, Fallin D, Feinberg AP. An integrated epigenetic and genetic approach to common human disease. Trends in Genetics, 20:350 358, 2004.
Gius D, Cui H, Bradbury C, Cook J, Smart DK, Shuping Z, Young L, Brandenburg S, Hu Y, Bisht K, Ho AS, Mattson D, Sun L, Munson PJ, Chuang EY, Mitchell JB, and Feinberg AP. Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach, Cancer Cell, 6:361-371, 2004.
Niemitz EL, DeBaun MR, Fallon J, Murakami K, Kugoh H, Oshimura M, and Feinberg AP. Microdeletion of LIT1 in familial Beckwith-Wiedemann syndrome. Am J Hum Genet, 75:844-849, 2004.
Niemitz EL and Feinberg AP. Epigenetics and assisted reproductive technology: A call for investigation. Am J Hum Genet, 74:599-609,2004.
Feinberg AP. The epigenetics of cancer etiology. Seminars in Cancer Biology, 14:427-432, 2004.
Sakatani T, Kaneda A, Iacobuzio-Donahue CA, Carter MD, deBoom Witzel S, Okano H, Ko MSH, Ohlsson R, Longo DL, and Feinberg AP. Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science, 307:1976-1978, 2005.
Feinberg AP, Ohlsson R, and Henikoff S. The epigenetic progenitor origin of human cancer. Nature Reviews Genetics, 7:21-33, 2006.
Andrew Feinberg, MD, MPHJohns Hopkins University School of Medicine
Center for Epigenetics
855 North Wolfe Street
Baltimore, MD 21205
Sr. Administrative Manager
Sr. Administrative Coordinator