PEGGY FARNHAM, PH.D.

PROFESSOR OF MEDICAL PHARMACOLOGY AND TOXICOLOGY

ADDRESS: UC Davis Genome Center Genome and Biomedical Sciences Facility
451 East Health Sciences Drive
Davis, CA 95616-8816
pjfarnham@ucdavis.edu

FORMAL EDUCATION:
B.A. with Honors, Biochemistry, Rice University, Houston, Texas, 1978
Ph.D., Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, 1982.

POSITIONS HELD:
NIH Predoctoral Trainee, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, 1978-1982.
Damon Runyon-Walter Winchell Postdoctoral Fellow, Department of Genetics Stanford University, Stanford, California, 1982-1983.
NIH Postdoctoral Fellow, Department of Biological Sciences, Stanford University, Stanford, California, 1983-1986.
Assistant Professor of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin, 1987 to 1992.
Associate Professor of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin, 1992 to 1997.
Chair, Cellular and Molecular Biology Ph.D. Degree Program University of Wisconsin, Madison, Wisconsin, 1996 to 2002
Professor of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin, 1997 to 2004
Professor of Medical Pharmacology and Toxicology, University of California, Davis, California, 2004-present

AWARDS AND HONORS
NIH Predoctoral Trainee, 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.
Associate Editor, Journal of Biological Chemistry, 2001-present
Secretary, American Society of Biochemistry and Molecular Biology, 2004-present



RESEARCH STATEMENT

My laboratory has been a leader in developing the technique of chromatin immunoprecipitation (ChIP) to study the function of mammalian transcription factors, such as c-Myc, E2Fs, and Polycomb Group complexes. Recently, we have extended these studies to allow a high throughput, global analysis of transcription factor target genes by combining chromatin immunoprecipitation with CpG microarray hybridization (ChIP-chip assays). We are currently developing high density oligonucleotide microarrays which will allow a comprehensive analysis of transcription factor binding sites and chromatin modifications on a genome-wide scale. Current projects include the analysis of changes in chromatin structure as embryonic stem cells differentiate, changes in chromatin structure in normal vs tumor cells, the identification of target genes of transcription factors such as Oct4 (a key regulator of stem cell self renewal), SUZ12 (a Polycomb Group protein involved in development and tumor progression), the retinoblastoma tumor suppressor protein (a key cell cycle regulator) and E2F6 (a transcriptional repressor).


FARNHAM PUBLICATIONS FROM 2000-PRESENT

Mac, S.M. and Farnham, P.J. Cad, a c-Myc target gene, is not deregulated in Burkitt’s lymphomas, Molecular Carcinogenesis 27: 84-96, 2000.
Lee, T.A. and Farnham, P.J. Exogenous E2F1 is growth inhibitory before, during, and after neoplastic transformation, Oncogene. 19:2257-2268, 2000.
Wells, J., Boyd, K.E., Fry, C.J., Bartley, S.M., and Farnham, P.J. Target gene specificity of E2F and pocket protein family members in living cells. Mol. Cell Biol. 20: 5987-5807, 2000.
Mac, S.M., D’Cunha, C., and Farnham, P.J. Direct recruitment of N-Myc to target gene promoters. Molecular Carcinogenesis 29:76-86, 2000.
Eberhardy, S.R. and Farnham, P.J. Direct examination of histone acetylation of c-Myc target genes using chromatin immunoprecipitation. J. Biol. Chem. 275: 33798-33805, 2000.
Graveel, C.R., Jatkoe, T., Madore, S., Holt, A.L., and Farnham, P.J. Expression profiling and identification of novel genes in hepatocellular carcinomas. Oncogene 20: 2704-2712-2001.
Kel, A.E., Kel-Margoulis, O.V., Bartley, S.M., Farnham, P.J., Wingender, E.,and Zhang, M.Q.. Computer-assisted identification of cell cycle-related genes - new targets for E2F transcription factors. J. Mol. Biol. 309: 99-120, 2001.
Albert, T., Wells, J., Funk, J.-O., Pullner, A., Raschke, E.-E., Stelzer, G., Meisterernst, M., Farnham, P.J., and Eick, D. Chromatin remodeling and acetylation of the dual c-myc promoters P1/P2 is regulated by separate elements. J. Biol. Chem. 276: 20482-20490, 2001.
Maser, R.S., Mirzoeva, O., Wells, J., Olivares, H., Williams, B., Zinkel, R., Farnham, P.J., and Petrini, J.H.J. The MRE11 complex: diverse roles in S phase progression. Mol. Cell. Biol. 21: 6006-6016, 2001.
Weinmann, A.S., Bartley, S.M., Zhang, M.Q., Zhang, T., and Farnham, P.J. The use of chromatin immunoprecipitation to clone novel E2F target promoters. Mol. Cell. Biol. 21: 6820-6832, 2001.
Eberhardy, S.R. and Farnham, P.J. c-Myc mediates activation of the cad promoter via a post-RNA polymerase II recruitment mechanism. J. Biol. Chem. 276:48562-48571, 2001.
Weinmann, A.S., Yan, P.S., Oberley, M.J., Huang, H.-M.T., and Farnham, P.J. Isolating human transcription factor targets by combining chromatin immunoprecipitation and CpG microarray analysis. Genes & Devel. 16:235-244, 2002
Wells, J., Graveel, C.R., Bartley, S.M., and Farnham, P.J. The identification of E2F1-specific target genes. Proc. Natl. Acad. Sci. USA, 99:3890-3895,2002.
Weinmann, A.S. and Farnham, P.J. Identification of unknown target genes of human transcription factors using chromatin immunoprecipitation. Methods 26:37-47, 2002.
Wells, J. and Farnham, P.J. Characterizing transcription factor binding sites using formaldehyde crosslinking and immunoprecipitation. Methods 26:48-56, 2002.
Eberhardy, S.R. and Farnham, P.J. Myc recruits P-TEFb to mediate the final step in the transcriptional activation of the cad promoter. J. Biol. Chem, 277: 40156-40162, 2002.
Kirmizis, A, Bartley, S.M., and Farnham, P.J. Identification of the Polycomb Group protein SU(Z)12 as a new _-catenin target gene which is upregulated in colon tumors. Mol. Cancer Therapeutics, 2:113-121, 2003.
Wells, J., Yan, P.S., Cechvala, M., Huang, H.-M.T, and Farnham, P.J. Identification of novel pRb binding sites using CpG microarrays suggests that E2F recruits pRb to specific genomic sites during S phase. Oncogene 22:1445-1460, 2003
Graveel, C.R., Harkins-Perry, S.R., Acevedo, L.G., and Farnham, P. J. Identification and characterization of CRG-L2, a new marker for liver tumor development. Oncogene 22:1730-1736, 2003.
Oberley, M.J. and Farnham, P. J. Probing chromatin immunoprecipitates with CpG island microarrays to identify genomic sites occupied by DNA-binding proteins. Methods in Enzymology 371:577-596, 2003.
Oberley, M.J., Tsao, J., Yau, P., and Farnham, P. J. High-throughput screening of chromatin immunoprecipitates using CpG-island microarrays. Methods in Enzymology 376: 315-333 2004.
Mao, D.Y. L., Watson, J.D., Yan, P.S., Barsyte-Lovejoy, D., Khosravi, F., Wong, W.W.-L., Farnham, P. J., Huang, T.H.-M., Penn, L.Z. Analysis of Myc bound loci identified by CpG island arrays shows that Max is essential for Myc-dependent repression. Current Biology 13;1-20, 2003.
Oberley, M.J., Inman, D.R., and Farnham, P.J. E2F6 negatively regulates BRCA1 in human cancer cells without methylation of histone H3 on lysine 9. Journal of Biological Chem. 278:42466-42476-2003.
Oberley MJ, Farnham PJ. Identification of mammalian E2F regulatory networks using DNA microarray hybridization analyses. In: Shannon MF, Rao S, eds. Microarrays and Transcription Networks. Georgetown: Landes Bioscience/Eurekah.com, 2004: In press.
Kirmizis, A., Bartley, S. M., Kuzmichev, A., Margueron R., Reinberg. R., Green, R., and Farnham, P. J. Silencing of human polycomb target genes is associated with methylation of histone H3 lysine 27. Genes & Devel. in press, 2004
Townsend, M. J., Weinmann, A. S., Matsuda, J., Saloman, R., Farnham, P., Biron, C. A., Gapin, L.,and Glimcher, L. H. T-bet regulates the terminal maturation and homeostasis of NK and V_14i NKT cells. Immunity, 20: 477-494.2004
Kirmizis, A. and Farnham, PJ. Genomic approaches that aid in the identification of transcription factor target genes. Proceedings Experimental Biology and Medicine, 2004: In press.
Farnham, PJ. New insights into transcriptional regulation by RB: One size no longer fits all. In: Fanciulli, M. ed. Rb Regulation of Oncogenesis, Georgetown: Landes Bioscience/Eurekah.com, 2004: In press.
Lavrrar, J.L. and Farnham, P. J. The use of transient chromatin immunoprecipitation assays to test models for E2F1-specific transcriptional activation. submitted



POSTDOCTORAL POSITIONS AVAILABLE
The National Human Genome Research Institute (NHGRI) recently initiated the Encyclopedia of DNA Elements (ENCODE) Project, the goal of which is to comprehensively identify sequence-based functional elements in the human genome. To begin, NHGRI has chosen 1% (30 Mb) of the human genome as a focus for analysis. The details of regions selected can be found at http://www.genome.gov/10005107. In collaboration with NimbleGen Systems Inc, the Farnham lab has been awarded a grant from the NHGRI to study the ENCODE region. The goals of our project are to use the NimbleGen maskless array technology to create oligonucleotide-based microarrays to be used for the discovery of in vivo genomic transcription factor binding sites. In brief, our experiments are based on using chromatin immunoprecipitation (ChIP) to selectively enrich for all the binding sites in the human genome of a particular transcription factor. After immunoprecipitation, the fragments are labeled and used to probe a genomic microarray (i.e. a ChIP-chip assay). Our initial results are quite promising (see below) and we are currently using the ChIP-chip assay: a) for gene and first exon discovery, b) to study chromatin modifications on a genome-wide scale, and c) to identify binding sites for transcription factors critical for proliferation of normal and cancer cells (e.g. E2F family members, components of Polycomb Repression Complexes, and Oct4). Our data will also be used to develop consensus sequences for transcription factor binding sites and to understand common promoter architectures. There are postdoctoral position openings in both the experimental and bioinformatics aspects of this, and related, projects.