Program Director/Principal Investigator (Last, First, Middle

):

Farnham, Peggy, Jo

BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2.

Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME POSITION TITLE

Peggy J. Farnham
eRA COMMONS USER NAME (credential, e.g., agency login)

Professor of Biochemistry and Mol. Biology University of Southern California

PJFARNHAM
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)

INSTITUTION AND LOCATION

DEGREE (if applicable)

MM/YY

FIELD OF STUDY

Rice University, Houston, TX Yale University, New Haven, CT Stanford University, Stanford, CA A. Personal Statement

B.A. Ph.D. Postdoc

05/78 05/82 12/86

Biochemistry Mol.Biophys.&Biochem Molecular Biology

My laboratory has been a leader in the genome-wide study of mammalian transcription factors by developing technologies that combine chromatin immunoprecipitation with genomic microarray hybridization (ChIP-chip assays) and with high throughput sequencing (ChIP-seq). We were the first to develop ChIP protocols for mammalian cells (Boyd and Farnham, 1997; Boyd et al., 1998) and for the study of tumors from cancer patients (Kirmizis et al. 2003). In 2001, we demonstrated that ChIP samples could be cloned and sequenced as an unbiased method to identify novel binding sites for human transcription factors (Weinmann et al. 2001) and in 2002 we demonstrated that spotted arrays containing CpG islands can be used for mammalian ChIP-chip experiments (Weinmann et al. 2002). In addition to bench work, my lab has developed programs to assist in the analysis of genome-scale ChIP-chip and ChIP-seq data and to derive consensus motifs from experimentally identified binding sites (Blahnik et al. 2010, Jin et al. 2009). I am a member of the ENCODE Consortium, whose goal is to map all the functional elements in the human genome. In the Pilot phase of ENCODE, I collaborated with NimbleGen Systems Inc to develop highdensity oligonucleotide arrays, being the first to demonstrate that NimbleGen oligonucleotide arrays can be used for ChIP-chip analysis (Kirmizis et al. 2004). More recently, my lab has been a major contributor to the production of ChIP-seq datasets for site-specific factors, histone-modifying complexes, and modified histones, developing protocols that are widely used (O’Geen et al. 2006, Acevedo et al. 2007, O’Geen et al. 2010, O’Geen et al. 2011). I have been awarded an ENCODE Technology grant to develop genomic nuclease assays to study distal regulatory regions in the human genome. I am also a member of the NIH Roadmap UC Reference Epigenome Mapping Center, whose goal is to characterize DNA methylation and histone modifications in a variety of primary cell types. My contributions to technology development and genome-wide analyses have been recently recognized by the ASBMB Herbert A. Sober Award for outstanding biochemical and molecular biological research. B. Positions, Memberships, and Honors Positions 1982-83: Damon Runyon-Walter Winchell Postdoc. Fellow, Genetics Dept, Stanford Univ., Stanford, CA 1983-86: NIH Postdoctoral Fellow, Dept. of Biological Sciences, Stanford Univ., Stanford, CA 1987-92: Assistant Professor, McArdle Laboratory for Cancer Research, Univ. of Wisconsin, Madison, WI 1992-97: Associate Professor, McArdle Laboratory for Cancer Research, Univ. of Wisconsin, Madison, WI 1996-01: Chair, Graduate Program in Cellular and Molecular Biology, Univ. of Wisconsin, Madison, WI 1997-04: Professor, McArdle Laboratory for Cancer Research, Univ. of Wisconsin, Madison, WI 2004-10: Professor, Pharmacology, Univ. of California, Davis, CA 2005-10: Associate Director of Genomics, UC Davis Genome Center 2011-present: William Keck Professor of Biochemistry, USC/Norris Cancer Center 2013-present: Associate Dean of Graduate Affairs, Keck School of Medicine at USC
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Biographical Sketch Format Page

Program Director/Principal Investigator (Last, First, Middle):

Farnham, Peggy, Jo

Other Experience and Professional Memberships Member: AAAS, ASM, ASBMB, and AACR Secretary, American Society of Biochemistry and Molecular Biology, 2004-2006 Member, Editorial Board, Journal of Biological Chemistry, 1996-2001 Associate Editor of Journal of Biological Chemistry, 2001-2006 Member, Editorial Board, Molecular and Cellular Biology, 1998-2006 Member, Editorial Board, Genome Research, 2008-present Member, Molecular Cytology Study Section, NIH, 1994-1998 Ad hoc reviewer, Molecular Biology Study Section, NIH, ongoing 2004-present: Member of NHGRI-sponsored ENCODE Consortium 2008-present: Member of NIH Roadmap Reference Epigenome Mapping Centers Honors NIH Predoctoral Fellow, 1978-1982. Damon Runyon-Walter Winchell Postdoctoral Fellow, 1982-1983. NIH Postdoctoral Fellow, 1983-1986. Outstanding Mentor in the U.W. Medical School, 1997, 1998 Vilas Associates Award, 1999-2000 Elected as AAAS Fellow in 2010 Appointed William M Keck Endowed Professor in 2011 ASBMB Herbert A. Sober Award in 2012; for outstanding biochemical and molecular biological research, with particular emphasis on development of methods and techniques to aid in research. Patents United States Patent 7,129,328 10/31/06 United States Patent 7,220,844 05/22/07 C. Selected publications (from 155 total publications) 1. Weinmann AS, Yan PS, Oberley MJ, Huang HMT, Farnham PJ. Isolating human transcription factor targets by combining chromatin immunoprecipitation and CpG microarray analysis. Genes & Dev. 16:235244,2002. PMC155318 Using CpG island microarrays, this manuscript provides the first demonstration that ChIP-chip can be used with human cells; given a “must read” ranking at Faculty of 1000: F1000.com/11799066. 2. Kirmizis A., Bartley SM, Kuzmichev A, Margueron R, Reinberg R, Green R, Farnham PJ. Silencing of human polycomb target genes is associated with methylation of histone H3 lysine 27. Genes & Devel. 18:1592-1605, 2004. PMC443521 This manuscript describes the first use of NimbleGen arrays for ChIP-chip and provides the first identification of human promoters epigenetically silenced by PRC2. 3. Bieda M, Xu S, Singer M, Green R, Farnham PJ. Unbiased Location Analysis of E2F1 Binding Sites Suggests a Widespread Role for E2F1 in the Human Genome. Genome Research, 16: 595-605, 2006. PMC145704 Using genome-scale ChIP-chip, this manuscript documents that E2F binding sites are dictated by proximity to RNAPII binding sites, rather than by the presence of a canonical motif; given a “must read” ranking at Faculty of 1000: F1000.com /1029798/. 4. Squazzo SL, Komashko VM, O’Geen H, Krig S, Jin VX, Jang S-W, Green R, Margueron R, Reinberg D, Farnham PJ. Suz12 silences large regions of the genome in a cell type-specific manner. Genome Research 16:890-900, 2006. PMC1484456 Using ChIP-chip, this manuscript demonstrates cell type-specificity of Suz12 target genes and provides the first evidence that PRC2 complexes can spread through large regions of mammalian genomes. 5. O’Geen H, Squazzo SL, Iyengar S, Blahnik K, Rinn JL, Chang HY, Green R, Farnham PJ. Genome-wide Analysis of KAP1 Binding Suggests an Auto-regulation of KRAB-ZNFs. PLOS Genetics 3, e89 doi:10.1371/journal.pgen.0030089, 2007. PMC1885280
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Program Director/Principal Investigator (Last, First, Middle):

Farnham, Peggy, Jo

A genome-scale ChIP-chip comparison of two epigenetic modifications in human cells revealed that zinc finger genes are bound by H3me3K9 and KAP1 and homeobox genes are bound by H3me3K27; given a “Recommended” ranking at Faculty of 1000: F1000.com /1087864/. 6. Rinn JL, Kertesz M, Wang J. Squazzo SL, Xu X, Brugmann S, Goodnough H, Helms JA, Farnham PJ, Segal E, Chang HY. Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Non-Coding RNAs. Cell 129, 1311-1323, 2007. PMC2084369 Dr. Farnham’s laboratory performed the epigenetic analyses of chromatin structure that helped to demonstrate a novel role for a non-coding RNA in regulating the human transcriptome; given an “Exceptional” ranking at Faculty of 1000: F1000.com/1088778. 7. Komashko VM, Acevedo LG, Squazzo SL, Iyengar SS, Rabinovich A, O’Geen H, Green R, Farnham PJ. Using ChIP-chip technology to reveal common principles of transcriptional repression in normal and cancer cells. Genome Research 18:521-532, 2008. PMC2279240 This study analyzes H3me3K27, H3me3K9, and DNA methylation in 12 different mammalian cell populations, demonstrating that, genes are generally silenced only by one type of epigenetic regulation. 8. Frietze S, O’Geen H, Blahnik KR, Jin VX, Farnham PJ. ZNF274 recruits the histone methyltransferase SETDB1 to the human genome. PLOS One, 5:e15082, 2010. PMID: 2117033. PMC2999557 This manuscript identifies the first KRAB-ZNF shown to recruit the SETDB1 epigenetic complex to specific sites in the human genome. 9. Iyengar S, Ivanov AV, Jin VX, Rauscher FJ III, Farnham, PJ. Functional analysis of KAP1 genomic recruitment. Molecular and Cellular Biology. 31:833-1847, 2011. PMID: 21343339 (PubMed-In process) This manuscript provides in vivo support for the model that KRAB-ZNFs recruit KAP1 to the genome via the N terminal RBCC domain. 10. Gerstein, !49 authors!, Farnham, Myers, Weissman, Snyder. Architecture of the human regulatory network derived from ENCODE data. Nature, 489:91-100, 2012. PMID:22955619 Dr. Farnham is a Consortium PI and her lab contributed ChIP-seq datasets used in this study. 11. Landt!41 authors! Farnham, Lieb, Wold, and Snyder. ChIP-seq guidelines and practices used by the ENCODE and modENCODE consortia. Genome Research, 22:1813-31, 2012. PMID:22955991 Dr. Farnham is a corresponding author on this manuscript and was instrumental in developing these guidelines. 12. Frietze S, Wang R, Tak YG, Gaddis M, Witt H, Farnham PJ, Jin VX. Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3. Genome Biology, 13:R52, 2012. PMID:22951069 Dr. Farnham is the corresponding author on this manuscript, which identifies TCF7L2 binding sites in 6 different types of human cancer cells and demonstrates that TCF7L2 marks the majority of enhancers in these cells. 13. Lan X, Witt H, Katsumura K, Ye Z, Wang Q, Bresnick EH, Farnham PJ*, Jin VX*. Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages. Nucleic Acids Res, 40:7690-7704, 2012. PMID:22675074 This manuscript describes a new method to integrate 3-dimensional chromosomal looping data with epigenomic marks and transcription factor binding sites. 14. THE ENCODE CONSORTIUM. An Integrated Encyclopedia of DNA Elements in the Human Genome. Nature, 489:57-74, 2012. PMID:22955616 This manuscript is an integrative analysis of data collected over the last 5 years by the ENCODE consortium. Dr. Farnham is a Consortium PI. 15. Blattler A, Yao L, Wang Y, Ye Z, Jin VX, Farnham PJ. ZBTB33 binds unmethylated regions of the genome associated with actively expressed genes. Epigenetics and Chromatin, 6:13, 2013 This manuscript shows that, contrary to prediction from in vitro studies, ZBTB33 does not bind to methylated DNA in vivo and does not contribute to gene silencing; rather it associates with active promoters.

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