Bernadett Papp, Ph.D
Department of Oral Biology
1395 Center Drive
Gainesville, FL 32610-0424
Phone: (352) 294-8752
- Ph.D., European Molecular Biology Laboratory (EMBL) & University of Heidelberg – Heidelberg, Germany (2006); MSc., University of Szeged – Szeged, Hungary (2002)
Papp Lab: Genome-wide Mechanisms of Cellular Identity in Health vs. Disease
The Papp laboratory focuses on discovering critical genome-wide molecular mechanisms that control the identity of cells. Cell identity changes naturally during development and during regeneration. However, deregulation of cellular identity can cause diseases such as developmental disorders and cancer. By defining the critical transcription factors, epigenetic regulators and signaling pathway circuits that control the cell fate changes, we may be able to pinpoint novel targets for therapies.
To this end, we apply state-of-the-art genomics approaches, single-cell imaging methods, functional genetics and biochemical approaches in various mouse and human cell types. Our approach is to (i) first perform an unbiased genome-wide study in order to (ii) identify key regulators of the complex process, (iii) which are then explored by functional studies leading to detailed mechanistic models. Our focus is on these key open questions:
- How is cellular identity maintained at the genome-wide level?
- What controls the establishment of novel cell fates at the genome-wide level?
- What genome-wide events drive cells towards disease development?
- How can cells adjust their functions during pathogen encounters?
- What mechanisms provide cells with flexibility to maintain their identities, while also giving them flexibility to react to new environments?
Signaling pathways governed genome-wide epigenetic mechanisms of reprogramming: Importantly, now we can also experimentally direct cell fate changes to our benefit. Generation of patient-specific cell types for therapeutic purposes is an important medical goal. This can be achieved by transcription factor-mediated reprogramming of somatic cells to embryonic stem cell-like induced pluripotent stem cells (iPSCs) or other differentiated cell types. My studies and others demonstrated that the reprogramming process is an excellent model system for characterizing the intricate links between cell identity and response to distinct signaling pathways from single-cell level to the global genomic level. Improper activation of signaling pathways during the reprogramming of somatic cells is a limiting factor for the generation of desired cell types. Thus, our ongoing efforts are to dissect the stage-specific functions of signaling regulators and cell type-specific transcriptional factors in reprogramming, which can lay the foundation for rational design of improved defined mediums to control cell fate changes, which is of high medical importance.
Genome-wide reprogramming of cellular identity during host-pathogen relations leading to disease: Cellular identity can be also altered due to environmental factors and pathogen encounters such as viral infections, which can also lead to various diseases including cancer. Currently, our main focus is to characterize governing principles maintaining cellular identity in the oral cavity, and to understand how oral cells respond to viral infections by adjusting their processes genome-wide. To this end, we have formed a synergistic collaboration with oncogenic virus experts of the laboratory of Dr. Zsolt Toth (Department of Oral Biology). My laboratory applies next-generation genomics approaches in order to understand how cells alter their functions genome-wide by adjusting their epigenetic and signaling pathways during viral infections. Recently, we have identified several novel players in viral infections, which are also involved in development and can be de-regulated in diseases such as cancer, but their functions as well as primary mechanisms triggering their de-regulations were unknown, which is an active area of investigation in my group.
Research Interest Keywords:
- Reprogramming mechanisms
- Cellular identity
- Signaling pathways and Epigenetic regulation of cell fate
- Host-Pathogen interactions
- Early events during Cancer development
Open positions in my lab:
Dr. Papp regularly mentor students at undergraduate to graduate level. She provides exciting research projects, direct mentorship with build-in flexibility to fit your curriculum, if you are a dedicated UF student with strong background in biology and interested in furthering your career towards future PhD – medical – dental research. Requirements: dedicate a rather substantial amount of time for laboratory work and commit long-term during your studies to my laboratory.
- Chronis C*, Fiziev* P, Papp B, Butz S, Bonora G, Sabri S, Ernst J, Plath K. (2017) Cooperative Binding of Transcription Factors Orchestrates Reprogramming. Cell, in press * co-first authorship
- Toth Z, Papp B, Brulois KF, Choi YJ, Gao SJ and Jung JU (2016) LANA-mediated recruitment of host Polycomb Repressive Complexes onto the KSHV genome during de novo infection. PLoS Pathogens, 12(9):e1005878. PMC5015872
- Pasque* V, Tchieu* J, Karnik R, Uyeda M, Dimashkie A, Case D, Papp B, Bonora G, Patel S, Ho R, Schmidt R, McKee R, Sado T, Tada T, Meissner A, and Plath (2014) X Chromosome Reactivation Dynamics Reveal Stages of Reprogramming to Pluripotency. Cell, 159:1681-1697. PMC4282187. * co-first authorship
- Papp B, Plath K (2013) Epigenetics of reprogramming to induced pluripotency. Cell, 152(6): 1324-43. PMC3602907. Review
- Ho* R, Papp* B, Hoffman J.A., Merill B.J., and Plath K. (2013) Stage-specific regulation of reprograming to iPSCs by Wnt signaling and Tcf proteins. Cell Reports, 3:2113-2126. PMC3700671 * co-first authorship
- Papp B, Plath K (2012) Pluripotency re-centered around Esrrb. The EMBO Journal, 31(22): 4255-7. PMC3501223
- Papp B, Plath K. (2011) Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape. Cell Research, 21(3):486-501. PMC3193418. Review
- Hiratani I, Ryba T, Itoh M, Rathjen J, Kulik M, Papp B, Fussner E, Bazett-Jones DP, Plath K, Dalton S, Rathjen PD, Gilbert DM. (2010) Genome-wide dynamics of replication timing revealed by in vitro models of mouse embryogenesis. Genome Research, 20(2):155-69. PMC2813472
- Gaytan A, Gutierrez L, Fritsch C, Papp B, Beuchle D, Müller, J (2007) A genetic screen identifies novel Polycomb group genes in Drosophila. Genetics, 2007 Aug; 176(4): 2099-108. PMC1950617
- Nekrasov M, Klymenko T, Fraterman S, Papp B, Oktaba K, Kocher T, Cohen A, Stunnenberg H, Wilm M, Müller, J (2007) Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes. The EMBO Journal, 2007 Sep 19:26(18):4078-88. PMC1964751
- Papp B. and Müller J. (2006). Histone tri-methylation and the maintenance of transcriptional ON and OFF states by PcG and trxG proteins. Genes & Development, 20(15):2041-54. PMC1536056
- Klymenko T, Papp B, Fischle W, Köcher T, Schelder M, Fritsch C, Wild B, Wilm M, Müller J. (2006) A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine binding activities. Genes & Development, 20(9): 1110-22. PMC1472471