Franklin Pugh

The Pugh lab aims to uncover fundamental molecular mechanisms of eukaryotic gene regulation. The lab studies how the transcription machinery assembles at promoters and the role that enhancers play in accelerating this assembly. Students use the latest biochemical, genetic, computational, and genomic technologies in yeast and human model systems. A heavy emphasis is placed on elucidating the precise genome-wide organization of regulatory proteins. This includes how sequence-specific transcription factors engage chromatin remodelers like SAGA, SWI/SNF, and Mediator to augment assembly of RNA polymerase II and general initiation factors like TFIID. In support of student projects and collaborations, the lab also conducts large-scale projects on mapping precisely where proteins interact with DNA along chromosomes. This provides a structural understanding of the protein-DNA architecture of chromosomes, and has necessitated the development of powerful computational approaches to analyze millions of ChIP-exo/seq and RNA-seq data values. Function is assessed through CRISPR/Cas9-engineered depletion of regulatory proteins, and through biochemical reconstitution of protein/DNA complexes on a genomic scale. One biomedical goal is to identify protein/DNA interactions that correlate with tissue disease and their treatment outcomes so as to develop improved medical diagnostics.

Recent Publications:

• John J, Jabbar J, Badjatia N, Rossi MJ, Lai WKM, Pugh BF. (2022). Genome-wide promoter assembly in E. coli measured at single-base resolution. Genome Res. 2022;32(5):878-92.
• Shao D, Kellogg GD, Nematbakhsh A, Kuntala PK, Mahony S, Pugh BF, Lai WKM. (2022). PEGR: a flexible management platform for reproducible epigenomic and genomic research. Genome Biol. 2022;23(1):99.
• Mittal C, Lang O, Lai WKM, Pugh BF. (2022). An integrated SAGA and TFIID PIC assembly pathway selective for poised and induced promoters. Genes Dev 36: 985-1001.
• Qi Sun , Ali Nematbakhsh , Prashant K. Kuntala, Gretta Kellogg, B. Franklin Pugh, William K. M. Lai (2022) STENCIL: A web templating engine for visualizing and sharing life science datasets. Computational Biology, in press.
• Zhao, T., Vvedenskaya, I.O., Lai, W.K., Basu, S., Pugh, B.F., Nickels, B.E., and Kaplan, C.D. (2021). Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae. Elife 10 :e71013
• Lai, W.K.M., Mariani, L., Rothschild, G., Smith, E.R., Venters, B.J., Blanda, T.R., Kuntala, P.K., Bocklund, K., Mairose, J., Dweikat, S.N., Mistretta, K., Rossi, M.J., James, D., Anderson, J.T., Phanor, S.K., Zhang, W., Shaw, A.P., Novitzky, K., McAnarney, E., Keogh, M.-C., Shilatifard, A., Basu, U., Bulyk, M.L., and Pugh, B.F. (2021). Screening of PCRP transcription factor antibodies in biochemical assays. Genome Res, 31, 1663-1679.
• Rossi, M.J., Kuntala, P.K., Lai, W.K.M., Yamada, N., Badjatia, N., Mittal, C., Kuzu, G., Bocklund, K., Farrell, N., Blanda, T.R., Mairose, J.D., Basting, A.V., Mistretta, K.S., Rocco, D.J., Perkinson, E.S., Kellogg, G.D., Mahony, S., and Pugh, B.F. (2021). A high-resolution protein architecture of the budding yeast genome. Nature, 592, 309-314.
• Badjatia, N., Rossi, M.J., Bataille, A.R., Mittal, C., Lai, W.K.M., and Pugh, B.F. (2021). Acute stress drives global repression through two independent RNA polymerase II stalling events in Saccharomyces. Cell Rep 34, 108640.
• Qiu C, Jin H, Vvedenskaya I, Llenas JA, Zhao T, Malik I, Visbisky AM, Schwartz SL, Cui P, Cabart P, Han KH, Lai WKM, Metz RP, Johnson CD, Sze SH, Pugh BF, Nickels BE, Kaplan CD. (2020). Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae. Genome Biol. 21, 132-.
• Shao, D., Kellogg, G.D., Lai, W.K.M., Mahony, S., and Pugh, B.F. (2020). PEGR: a management platform for ChIP-based next generation sequencing pipelines. In Practice and Experience in Advanced Research Computing (Portland, OR, USA, Association for Computing Machinery), pp. 285-292.
• Kumar, A., Zhong, Y., Albrecht, A., Sang, P.B., Maples, A., Liu, Z., Vinayachandran, V., Reja, R., Lee, C.F., Kumar, A., Chen, J., Xiao, J., Park, B., Shen, J., Liu, B., Person, M.D., Trybus, K.M., Zhang, K.Y.J., Pugh, B.F., Kamm, K.E., Milewicz, D.M., Shen, X., and Kapoor, P. (2020). Actin R256 Mono-methylation Is a Conserved Post-translational Modification Involved in Transcription. Cell Rep 32, 108172.
• Yamada N, Rossi MJ, Farrell N, Pugh BF, Mahony S. (2020) Alignment and quantification of ChIP-exo crosslinking patterns reveal the spatial organization of protein-DNA complexes. Nucleic Acids Res. 48, 11215-11226. PMC7672471
•  Qiu C, Jin H, Vvedenskaya I, Llenas JA, Zhao T, Malik I, Visbisky AM, Schwartz SL, Cui P, Čabart P, Han KH, Lai WKM, Metz RP, Johnson CD, Sze SH, Pugh BF, Nickels BE, Kaplan CD. (2020) Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae. Genome Biol. 21, 132. PMID: 32487207
• Yamada N, Kuntala PK, Pugh BF, Mahony S (2020) ChExMix: A Method for Identifying and Classifying Protein-DNA Interaction Subtypes. Comput Biol. 27, 429-435. PMID: 32023130
• Gallego LD, Schneider M, Mittal C, Polyansky AA, Romanauska A, Gudino-Carillo RM, Schubert T, Zagrovic B, Pugh, BF, Kohler, A. (2020) Liquid-liquid phase separation directs ubiquitination of gene body nucleosomes. Nature 579, 592-597. PMID: 3221424

• 1988-1991 Leukemia & Lymphoma Society Postdoctoral Fellow
• 1992-1995 Searle Scholar
• 1996-2001 Leukemia & Lymphoma Society Scholar
• 2004-2020 Director, Center for Eukaryotic Gene Regulation, Penn State
• 2007-2020 Verne M. Willaman Chair in Molecular Biology, Penn State
• 2008-2018 Editor, Molecular and Cellular Biology2014-2020Evan Pugh University Professor, Penn State
• 2014-present Fellow, AAAS
• 2020-present Greater Philadelphia Professor of Biological Sciences, Cornell University

Dr. Pugh specializes in teaching undergraduate and graduate courses in Molecular and Cellular Biology.