Researcher Profile

Researcher Profile

George-Lucian Moldovan, PhD

George-Lucian Moldovan, PhD

Associate Professor, Department of Biochemistry and Molecular Biology
Assistant Professor, Department of Biochemistry and Molecular Biology
Scientific Program:Experimental Therapeutics
glm29@psu.edu

Research Interests

Dr. George-Lucian Moldovan’s major research goal is to elucidate the molecular mechanism of replication of DNA lesions in human cells, using an integrative approach that includes:

  • identification of the factors involved in detection and processing of stalled forks;
  • biochemical reconstitution of discrete steps of the fork restart process; and
  • genetic analyses to assess the role of these processes in genomic stability, cellular transformation, and cancer prevention and therapy.

For all organisms, the information necessary for living and propagation is encoded in their genomes. Maintaining and transferring stable genomes to the progeny is thus essential. In humans, failure to preserve the correct DNA sequence can result in cellular transformation and cancer, as well as degeneration and accelerated aging. To avoid genomic instability, cells employ numerous mechanisms that detect, signal and repair DNA lesions. These mechanisms also stabilize and protect complex macromolecular structures such as replication forks (which form during DNA duplication) and ensure the correct and timely replication and segregation of chromosomes. They are subjected to complex cellular regulation and are frequently inactivated in cancer.

In particular, DNA replication is a complex process that requires tight regulation to ensure genomic stability. Replication of damaged DNA poses a great risk, since DNA lesions cannot be processed by regular replicative polymerases and thus result in stalling of the replication machinery. Understanding how the replication machinery deals with roadblocks is fundamental, since prolonged replication stalling can result in strand breaks, translocations, and genomic instability. What ultimately dictates the fate of stalled forks is not understood and in fact remains one of the biggest unsolved mysteries in cell biology.

To resolve this conundrum, the missing components of this regulatory circuit must be identified and characterized.

  • Proliferating Cell Nuclear Antigen
  • DNA Repair
  • DNA
  • DNA Damage
  • Neoplasms
  • Genomic Instability
  • DNA Replication
  • Proteins
  • DNA-Directed DNA Polymerase
  • Ubiquitin
  • Fanconi Anemia
  • S Phase

Recent Publications

2019

Naldiga, S, Ji, S, Thomforde, J, Nicolae, C, Lee, M, Zhang, Z, Moldovan, G-L, Tretyakova, NY & Basu, AK 2019, 'Error-prone replication of a 5-formylcytosine-mediated DNA-peptide cross-link in human cells', Journal of Biological Chemistry, vol. 294, no. 27, pp. 10619-10627. https://doi.org/10.1074/jbc.RA119.008879
Edvardson, S, Nicolae, C, Noh, GJ, Burton, JE, Punzi, G, Shaag, A, Bischetsrieder, J, De Grassi, A, Pierri, CL, Elpeleg, O & Moldovan, G-L 2019, 'Heterozygous RNF13 Gain-of-Function Variants Are Associated with Congenital Microcephaly, Epileptic Encephalopathy, Blindness, and Failure to Thrive' American Journal of Human Genetics, vol. 104, no. 1, pp. 179-185. https://doi.org/10.1016/j.ajhg.2018.11.018
Leung, W, Baxley, RM, Moldovan, G-L & Bielinsky, AK 2019, 'Mechanisms of DNA damage tolerance: post-translational regulation of PCNA', Genes, vol. 10, no. 1, 10. https://doi.org/10.3390/genes10010010
Nicolae, C, O’Connor, MJ, Schleicher, EM, Song, C, Gowda, R, Robertson, G, Dovat, S & Moldovan, G-L 2019, 'PARI (PARPBP) suppresses replication stress-induced myeloid differentiation in leukemia cells', Oncogene, vol. 38, no. 27, pp. 5530-5540. https://doi.org/10.1038/s41388-019-0810-x
Ranoa, DRE, Widau, RC, Mallon, S, Parekh, AD, Nicolae, C, Huang, X, Bolt, MJ, Arina, A, Parry, R, Kron, SJ, Moldovan, G-L, Khodarev, NN & Weichselbaum, RR 2019, 'STING promotes homeostasis via regulation of cell proliferation and chromosomal stability', Cancer Research, vol. 79, no. 7, pp. 1465-1479. https://doi.org/10.1158/0008-5472.CAN-18-1972

2018

Barnes, RP, Tsao, WC, Moldovan, G-L & Eckert, K 2018, 'DNA polymerase eta prevents tumor cell-cycle arrest and cell death during recovery from replication stress', Cancer Research, vol. 78, no. 23, pp. 6549-6560. https://doi.org/10.1158/0008-5472.CAN-17-3931
Clements, KE, Thakar, T, Nicolae, C, Liang, X, Wang, H-G & Moldovan, G-L 2018, 'Loss of E2F7 confers resistance to poly-ADP-ribose polymerase (PARP) inhibitors in BRCA2-deficient cells', Nucleic acids research, vol. 46, no. 17, pp. 8898-8907. https://doi.org/10.1093/nar/gky657
Nicolae, C, O'connor, MJ, Constantin, D & Moldovan, G-L 2018, 'NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation', Oncogene, vol. 37, no. 27, pp. 3647-3656. https://doi.org/10.1038/s41388-018-0219-y
Schleicher, EM, Galvan, AM, Imamura, Y, Moldovan, G-L & Nicolae, C 2018, 'PARP10 promotes cellular proliferation and tumorigenesis by alleviating replication stress', Nucleic acids research, vol. 46, no. 17, pp. 8908-8916. https://doi.org/10.1093/nar/gky658

2017

Choe, KN & Moldovan, G-L 2017, 'Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork', Molecular cell, vol. 65, no. 3, pp. 380-392. https://doi.org/10.1016/j.molcel.2016.12.020
Edvardson, S, Nicolae, C, Agrawal, PB, Mignot, C, Payne, K, Prasad, AN, Prasad, C, Sadler, L, Nava, C, Mullen, TE, Begtrup, A, Baskin, B, Powis, Z, Shaag, A, Keren, B, Moldovan, G-L & Elpeleg, O 2017, 'Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood', American Journal of Human Genetics, vol. 101, no. 2, pp. 267-273. https://doi.org/10.1016/j.ajhg.2017.07.002

2016

Nicolae, C & Moldovan, G-L 2016, 'ERKing Trypanosoma: PCNA phosphorylation as novel target' Cell Cycle, vol. 15, no. 23, pp. 3167-3168. https://doi.org/10.1080/15384101.2016.1232081
Shahrour, MA, Nicolae, C, Edvardson, S, Ashhab, M, Galvan, AM, Constantin, D, Abu-Libdeh, B, Moldovan, G-L & Elpeleg, O 2017, 'Erratum to: PARP10 deficiency manifests by severe developmental delay and DNA repair defect (Neurogenetics, (2016), 17, (227-232), 10.1007/s10048-016-0493-1)' Neurogenetics, vol. 18, no. 1. https://doi.org/10.1007/s10048-016-0503-3
Choe, KN, Nicolae, C, Constantin, D, Imamura, Y, Delgado-Diaz, MR, De, S, Freire, R, Smits, VA & Moldovan, G-L 2016, 'HUWE1 interacts with PCNA to alleviate replication stress', EMBO Reports, vol. 17, no. 6, pp. 874-886. https://doi.org/10.15252/embr.201541685
Shahrour, MA, Nicolae, C, Edvardson, S, Ashhab, M, Galvan, AM, Constantin, D, Abu-Libdeh, B, Moldovan, G-L & Elpeleg, O 2016, 'PARP10 deficiency manifests by severe developmental delay and DNA repair defect', Neurogenetics, vol. 17, no. 4, pp. 227-232. https://doi.org/10.1007/s10048-016-0493-1
Cukras, S, Lee, E, Palumbo, E, Benavidez, P, Moldovan, G-L & Kee, Y 2016, 'The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair', Cell Cycle, vol. 15, no. 19, pp. 2636-2646. https://doi.org/10.1080/15384101.2016.1209613

2015

Nicolae, C, Aho, ER, Choe, KN, Constantin, D, Hu, HJ, Lee, D, Myung, K & Moldovan, G-L 2015, 'A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting homologous recombination and protecting against replication stress' Nucleic acids research, vol. 43, no. 6, pp. 3143-3153. https://doi.org/10.1093/nar/gkv147
Gowda, ASP, Moldovan, G-L & Spratt, T 2015, 'Human DNA polymerase ν catalyzes correct and incorrect DNA synthesis with high catalytic efficiency', Journal of Biological Chemistry, vol. 290, no. 26, pp. 16292-16303. https://doi.org/10.1074/jbc.M115.653287

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