Papp Lab: Genome-Wide Switch Mechanisms in Health vs. Disease
The Papp laboratory focuses on discovering critical genome-wide molecular mechanisms that control cellular functions. Cell identity changes naturally during development and during regeneration. However, deregulation of cellular identity can cause diseases such as developmental disorders and cancer. Cellular identity can be also altered due to environmental factors and pathogen encounters such as viral infections, which can also lead to diseases. We characterize governing principles maintaining cellular identity in various context, including the oral cavity. We aim to find out how cells respond to viral infections genome-wide, and what mechanisms control outcome of viral infections. By defining the critical transcription factors, epigenetic regulators and signaling pathway circuits that control cell fate changes and host-pathogen interactions, we may be able to pinpoint novel targets for therapies. To this end, we apply state-of-the-art genomics approaches, imaging methods, functional genetics and biochemical approaches. 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?
- What controls the establishment of novel cellular functions?
- What master regulators (transcription factors, epigenetic factors and signaling pathways) determine outcome of viral infections?
- What functions are altered during pathogen encounters and how?
- What events drive cells towards disease development, such as cancer?
Research Interest Keywords
- Reprogramming mechanisms
- Cell identity
- Host-Pathogen interactions
- Viral infections
- Mechanisms of oncogenesis
# indicates corresponding author
- Atyeo N*, Rodriguez MD*, Papp B# and Toth Z# (2021) Clinical Manifestations and Epigenetic Regulation of Oral Herpesvirus Infections. Viruses, 2021 Apr 15; 13(4): 681 *contributed equally
- Pandya-Jones A, Markaki Y, Serizay J, Chitiashvili T, Walter M, Damianov A, Chronis K, Papp B, Chen CK, McKee R, Wang XJ, Chau A, Leonhardt H, Zheng Sika, Guttman M, Black DL, Plath K (2020) An Xist-dependent protein assembly mediates Xist localization and gene silencing. Nature, 587, 145-151
- Naik NG*, Nguyen TH*, Roberts L, Fischer LT, Glickman K, Golas G, Papp B#, Toth Z#. (2020) Epigenetic factor siRNA screen during primary KSHV infection identifies novel host restriction factors for the lytic cycle of KSHV. PLoS Pathog. 10;16(1):e1008268. *contributed equally
- Golas G*, Jang SJ*, Naik NG, Alonso JD, Papp B, Toth Z (2020) Comparative analysis of the viral interferon regulatory factors of KSHV for their requisite for virus production and inhibition of the type I interferon pathway. Virology (541): 160-173. *contributed equally
- Papp B#, Motlagh N, Smindak R, Jang SJ, Sharma A, Alonso JD, Toth Z# (2019) Genome-wide identification of direct RTA targets reveals key host factors for KSHV lytic reactivation. Journal of Virology, 2019 Mar 1; 93(5): e01978-18
- Chronis C*, Fiziev P*, Papp B, Butz S, Bonora G, Sabri S, Ernst J, and Plath K (2017) Cooperative binding of Oct4, Sox2, Klf4 and stage-specific transcription factors orchestrates reprogramming. Cell 168(3):442-459. Epub 2017 Jan 19. *contributed equally
- 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