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Dr. Andrew Feinberg

M.D., M.P.H.
Andrew Feinberg
Titles

King Fahd Professor of Medicine, Molecular Biology and Genetics, and Oncology

Schools\Degrees

MD, The Johns Hopkins University MPH, The Johns Hopkins University

Training

Intern, Medicine, Hospital of the University of Pennsylvania
Research Fellow, Neurosciences, University of California, San Diego
Clinical and Research Fellow, Medicine (Medical Genetics) and Oncology (Cancer Genetics), Johns Hopkins University School of Medicine

Certifications

Internal Medicine, Medical Genetics, and National Board of Medical Examiners

Research Summary

Our laboratory is exploring the epigenetic mechanism of human disease. 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 most of the differences between a germ cell and a somatic cell, or two different tissue types, or a cancer and a normal cell do not involve the DNA sequence but epigenetic changes. Part of our work is on the epigenetics of cancer. We earlier discovered 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 fraction of colorectal cancer. We have recently developed an animal model for epigenetic effects on cancer risk, and we have found a link between cancer risk and stem cell development. We have also identified the molecular basis of Beckwith-Wiedemann syndrome (BWS), a childhood disorder of birth defects and cancer that is caused by epigenetic alterations in two genes (IGF2, LIT1) and mutations in a third (p57/KIP2). We have found a link between in vitro fertilization and BWS, and we are developing animal models for the epigenetic basis of birth defects. We are also exploring a novel hypothesis of common human disease, in which the age-dependent stability of epigenetic marks contributes to complex traits involved in late onset diseases, such as diabetes, autism and bipolar disease. This work is based in a Genome Center awarded by the NIH, and we are developing new genome-level epigenetic (epigenomic) technology, new statistical measures of population-based epigenetics, and the application of these tools to human populations, including an outstanding epidemiological resource in Iceland. Trainees in the Center will perform multidisciplinary research and work closely with our collaborators in determining the epigenetic mechanism of common human disease.

 

Journal Citations

Bjornsson, H.T.; Brown, L.J.; Fallin, M.D.; Rongione, M.A.; Bibikova, M.; Wickham, E.; Fan, J.B.; Feinberg, A.P. Epigenetic specificity of loss of imprinting of the IGF2 gene in Wilms tumors. J Natl Cancer Inst. 2007 Aug 15;99(16):1270-1273.

Cianfrocca, M.; Wolff, A.C. Optimizing endocrine therapy for premenopausal and postmenopausal women with breast cancer. Oncology (Williston Park). 2007 Jan;21(1):63-69; discussion 69, 72, 75 passim.

Feinberg, A.P. Phenotypic plasticity and the epigenetics of human disease. Nature. 2007 May 24;447(7143):433-440.

Feinberg, A.P. An epigenetic approach to cancer etiology. Cancer J. 2007 Jan-Feb;13(1):70-74.

Kaneda, A.; Wang, C.J.; Cheong, R.; Timp, W.; Onyango, P.; Wen, B.; Iacobuzio-Donahue, C.A.; Ohlsson, R.; Andraos, R.; Pearson, M.A.; Sharov, A.A.; Longo, D.L.; Ko, M.S.; Levchenko, A.; Feinberg, A.P. Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20926-20931.

Ladd-Acosta, C.; Pevsner, J.; Sabunciyan, S.; Yolken, R.H.; Webster, M.J.; Dinkins, T.; Callinan, P.A.; Fan, J.B.; Potash, J.B.; Feinberg, A.P. DNA methylation signatures within the human brain. Am J Hum Genet. 2007 Dec;81(6):1304-1315.

Bjornsson, H.T.; Albert, T.J.; Ladd-Acosta, C.M.; Green, R.D.; Rongione, M.A.; Middle, C.M.; Irizarry, R.A.; Broman, K.W.; Feinberg, A.P. SNP-specific array-based allele-specific expression analysis. Genome Res. 2008 May;18(5):771-779.

Bjornsson, H.T.; Sigurdsson, M.I.; Fallin, M.D.; Irizarry, R.A.; Aspelund, T.; Cui, H.; Yu, W.; Rongione, M.A.; Ekstrom, T.J.; Harris, T.B.; Launer, L.J.; Eiriksdottir, G.; Leppert, M.F.; Sapienza, C.; Gudnason, V.; Feinberg, A.P. Intra-individual change over time in DNA methylation with familial clustering. Jama. 2008 Jun 25;299(24):2877-2883.

Feinberg, A.P. Epigenetics at the epicenter of modern medicine. Jama. 2008 Mar 19;299(11):1345-1350.

Irizarry, R.A.; Ladd-Acosta, C.; Carvalho, B.; Wu, H.; Brandenburg, S.A.; Jeddeloh, J.A.; Wen, B.; Feinberg, A.P. Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res. 2008 May;18(5):780-790.

Potash, J.B.; Buervenich, S.; Cox, N.J.; Zandi, P.P.; Akula, N.; Steele, J.; Rathe, J.A.; Avramopoulos, D.; Detera-Wadleigh, S.D.; Gershon, E.S.; DePaulo, J.R., Jr.; Feinberg, A.P.; McMahon, F.J. Gene-based SNP mapping of a psychotic bipolar affective disorder linkage region on 22q12.3: association with HMG2L1 and TOM1. Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):59-67.

Schreiner, B.; Bailey, S.L.; Shin, T.; Chen, L.; Miller, S.D. PD-1 ligands expressed on myeloid-derived APC in the CNS regulate T-cell responses in EAE. Eur J Immunol. 2008 Oct;38(10):2706-2717.

Wen, B.; Wu, H.; Bjornsson, H.; Green, R.D.; Irizarry, R.; Feinberg, A.P. Overlapping euchromatin/heterochromatin- associated marks are enriched in imprinted gene regions and predict allele-specific modification. Genome Res. 2008 Nov;18(11):1806-1813.

Yu, W.; Gius, D.; Onyango, P.; Muldoon-Jacobs, K.; Karp, J.; Feinberg, A.P.; Cui, H. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. 2008 Jan 10;451(7175):202-206.

Cruz-Correa, M.; Zhao, R.; Oviedo, M.; Bernabe, R.D.; Lacourt, M.; Cardona, A.; Lopez-Enriquez, R.; Wexner, S.; Cuffari, C.; Hylind, L.; Platz, E.; Cui, H.; Feinberg, A.P.; Giardiello, F.M. Temporal stability and age-related prevalence of loss of imprinting of the insulin-like growth factor-2 gene. Epigenetics. 2009 Feb;4(2):114-118.

Doi, A.; Park, I.H.; Wen, B.; Murakami, P.; Aryee, M.J.; Irizarry, R.; Herb, B.; Ladd-Acosta, C.; Rho, J.; Loewer, S.; Miller, J.; Schlaeger, T.; Daley, G.Q.; Feinberg, A.P. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat Genet. 2009 Dec;41(12):1350-1353.

Feinberg, A.P. Genome-scale approaches to the epigenetics of common human disease. Virchows Arch. 2009 Oct 21.

Irizarry, R.A.; Ladd-Acosta, C.; Wen, B.; Wu, Z.; Montano, C.; Onyango, P.; Cui, H.; Gabo, K.; Rongione, M.; Webster, M.; Ji, H.; Potash, J.B.; Sabunciyan, S.; Feinberg, A.P. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009 Feb;41(2):178-186.

Irizarry, R.A.; Wu, H.; Feinberg, A.P. A species-generalized probabilistic model-based definition of CpG islands. Mamm Genome. 2009 Sep 24.

Timp, W.; Levchenko, A.; Feinberg, A.P. A new link between epigenetic progenitor lesions in cancer and the dynamics of signal transduction. Cell Cycle. 2009 Feb 1;8(3):383-390.

Wen, B.; Wu, H.; Shinkai, Y.; Irizarry, R.A.; Feinberg, A.P. Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet. 2009 Feb;41(2):246-250.

Feinberg, A.P. Genome-scale approaches to the epigenetics of common human disease. Virchows Arch. 2010 Jan;456(1):13-21.

Feinberg, A.P. Epigenomics reveals a functional genome anatomy and a new approach to common disease. Nat Biotechnol. 2010 Oct;28(10):1049-1052.

Feinberg, A.P.; Irizarry, R.A.; Fradin, D.; Aryee, M.J.; Murakami, P.; Aspelund, T.; Eiriksdottir, G.; Harris, T.B.; Launer, L.; Gudnason, V.; Fallin, M.D. Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med. 2010 Sep 15;2(49):49ra67

Ji, H.; Ehrlich, L.I.; Seita, J.; Murakami, P.; Doi, A.; Lindau, P.; Lee, H.; Aryee, M.J.; Irizarry, R.A.; Kim, K.; Rossi, D.J.; Inlay, M.A.; Serwold, T.; Karsunky, H.; Ho, L.; Daley, G.Q.; Weissman, I.L.; Feinberg, A.P. Comprehensive methylome map of lineage commitment from haematopoietic progenitors. Nature. 2010 Sep 16;467(7313):338-342.

Kim, K.; Doi, A.; Wen, B.; Ng, K.; Zhao, R.; Cahan, P.; Kim, J.; Aryee, M.J.; Ji, H.; Ehrlich, L.I.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K.C.; Hongguang, H.; McKinney-Freeman, S.; Naveiras, O.; Yoon, T.J.; Irizarry, R.A.; Jung, N.; Seita, J.; Hanna, J.; Murakami, P.; Jaenisch, R.; Weissleder, R.; Orkin, S.H.; Weissman, I.L.; Feinberg, A.P.; Daley, G.Q. Epigenetic memory in induced pluripotent stem cells. Nature. 2010 Sep 16;467(7313):285-290.

Ladd-Acosta, C.; Aryee, M.J.; Ordway, J.M.; Feinberg, A.P. Comprehensive high-throughput arrays for relative methylation (CHARM). Curr Protoc Hum Genet. 2010 Apr;Chapter 20:Unit 20 21 21-19.

Lennerz, J.K.; Timmerman, R.J.; Grange, D.K.; DeBaun, M.R.; Feinberg, A.P.; Zehnbauer, B.A. Addition of H19 'loss of methylation testing' for Beckwith-Wiedemann syndrome (BWS) increases the diagnostic yield. J Mol Diagn. 2010 Sep;12(5):576-588.

Wu, H.; Caffo, B.; Jaffee, H.A.; Irizarry, R.A.; Feinberg, A.P. Redefining CpG islands using hidden Markov models. Biostatistics. 2010 Jul;11(3):499-514.

Cianfrocca, M.; Lee, S.; Von Roenn, J.; Rudek, M.A.; Dezube, B.J.; Krown, S.E.; Sparano, J.A. Pilot study evaluating the interaction between paclitaxel and protease inhibitors in patients with human immunodeficiency virus-associated Kaposi's sarcoma: an Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium (AMC) trial. Cancer Chemother Pharmacol. 2011 Jan 5.

 

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