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George-Lucian Moldovan, PhD

George-Lucian Moldovan, PhD

Associate Professor, Department of Biochemistry and Molecular Biology
Professor, Department of Biochemistry and Molecular Biology
Assistant Professor, Department of Biochemistry and Molecular Biology
Scientific Program:Next-Generation Therapies

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
  • Neoplasms
  • DNA Damage
  • DNA Repair
  • DNA
  • Genomic Instability
  • DNA Replication
  • Genome
  • Proteins
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • ADP Ribose Transferases
  • DNA-Directed DNA Polymerase

Recent Publications


Nusawardhana, A, Pale, LM, Nicolae, CM & Moldovan, GL 2024, 'USP1-dependent nucleolytic expansion of PRIMPOL-generated nascent DNA strand discontinuities during replication stress', Nucleic acids research, vol. 52, no. 5, pp. 2340-2354.


Wang, YC, Kelso, AA, Karamafrooz, A, Chen, YH, Chen, WK, Cheng, CT, Qi, Y, Gu, L, Malkas, L, Taglialatela, A, Kung, HJ, Moldovan, GL, Ciccia, A, Stark, JM & Ann, DK 2023, 'Arginine shortage induces replication stress and confers genotoxic resistance by inhibiting histone H4 translation and promoting PCNA ubiquitination', Cell Reports, vol. 42, no. 4, 112296.
Leung, W, Baxley, RM, Traband, E, Chang, YC, Rogers, CB, Wang, L, Durrett, W, Bromley, KS, Fiedorowicz, L, Thakar, T, Tella, A, Sobeck, A, Hendrickson, EA, Moldovan, GL, Shima, N & Bielinsky, AK 2023, 'FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination', Cell Reports, vol. 42, no. 12, 113523.
Hale, A, Dhoonmoon, A, Straka, J, Nicolae, CM & Moldovan, GL 2023, 'Multi-step processing of replication stress-derived nascent strand DNA gaps by MRE11 and EXO1 nucleases', Nature communications, vol. 14, no. 1, 6265.
Khatib, JB, Nicolae, CM & Moldovan, GL 2024, 'Role of Translesion DNA Synthesis in the Metabolism of Replication-associated Nascent Strand Gaps', Journal of Molecular Biology, vol. 436, no. 1, 168275.


Khatib, JB, Schleicher, EM, Jackson, LM, Dhoonmoon, A, Moldovan, GL & Nicolae, CM 2022, 'Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival', Oncotarget, vol. 13, no. 1, pp. 1078-1091.
Thakar, T, Dhoonmoon, A, Straka, J, Schleicher, EM, Nicolae, CM & Moldovan, GL 2022, 'Lagging strand gap suppression connects BRCA-mediated fork protection to nucleosome assembly through PCNA-dependent CAF-1 recycling', Nature communications, vol. 13, no. 1, 5323.
Jackson, LM & Moldovan, GL 2022, 'Mechanisms of PARP1 inhibitor resistance and their implications for cancer treatment', NAR Cancer, vol. 4, no. 4, zcac042.
Abu-Libdeh, B, Jhujh, SS, Dhar, S, Sommers, JA, Datta, A, Longo, GMC, Grange, LJ, Reynolds, JJ, Cooke, SL, McNee, GS, Hollingworth, R, Woodward, BL, Ganesh, AN, Smerdon, SJ, Nicolae, CM, Durlacher-Betzer, K, Molho-Pessach, V, Abu-Libdeh, A, Meiner, V, Moldovan, GL, Roukos, V, Harel, T, Brosh, RM & Stewart, GS 2022, 'RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1', Journal of Clinical Investigation, vol. 132, no. 5, e147301.
Dhoonmoon, A, Nicolae, CM & Moldovan, GL 2022, 'The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1', Nature communications, vol. 13, no. 1, 5063.
Schleicher, EM, Dhoonmoon, A, Jackson, LM, Khatib, JB, Nicolae, CM & Moldovan, GL 2022, 'The TIP60-ATM axis regulates replication fork stability in BRCA-deficient cells', Oncogenesis, vol. 11, no. 1, 33.
Hirschler-Laszkiewicz, I, Festa, F, Huang, S, Moldovan, GL, Nicolae, C, Dhoonmoon, A, Bao, L, Keefer, K, Chen, SJ, Wang, HG, Cheung, JY & Miller, BA 2022, 'The human ion channel TRPM2 modulates cell survival in neuroblastoma through E2F1 and FOXM1', Scientific reports, vol. 12, no. 1, 6311.


Lüscher, B, Ahel, I, Altmeyer, M, Ashworth, A, Bai, P, Chang, P, Cohen, M, Corda, D, Dantzer, F, Daugherty, MD, Dawson, TM, Dawson, VL, Deindl, S, Fehr, AR, Feijs, KLH, Filippov, DV, Gagné, JP, Grimaldi, G, Guettler, S, Hoch, NC, Hottiger, MO, Korn, P, Kraus, WL, Ladurner, A, Lehtiö, L, Leung, AKL, Lord, CJ, Mangerich, A, Matic, I, Matthews, J, Moldovan, GL, Moss, J, Natoli, G, Nielsen, ML, Niepel, M, Nolte, F, Pascal, J, Paschal, BM, Pawłowski, K, Poirier, GG, Smith, S, Timinszky, G, Wang, ZQ, Yélamos, J, Yu, X, Zaja, R & Ziegler, M 2022, 'ADP-ribosyltransferases, an update on function and nomenclature', FEBS Journal, vol. 289, no. 23, pp. 7399-7410.
Weissenrieder, JS, Reed, JL, Moldovan, GL, Johnson, MT, Trebak, M, Neighbors, JD, Mailman, RB & Hohl, RJ 2021, 'Antipsychotic drugs elicit cytotoxicity in glioblastoma multiforme in a calcium-dependent, non-D2 receptor-dependent, manner', Pharmacology Research and Perspectives, vol. 9, no. 3, e00689.
Schleicher, EM & Moldovan, GL 2022, 'CRISPR screens guide the way for PARP and ATR inhibitor biomarker discovery', FEBS Journal, vol. 289, no. 24, pp. 7854-7868.
Jackson, LM, Dhoonmoon, A, Hale, A, Dennis, KA, Schleicher, EM, Nicolae, CM & Moldovan, GL 2021, 'Loss of MED12 activates the TGFβ pathway to promote chemoresistance and replication fork stability in BRCA-deficient cells', Nucleic acids research, vol. 49, no. 22, pp. 12855-12869.
O’Connor, MJ, Thakar, T, Nicolae, CM & Moldovan, GL 2021, 'PARP14 regulates cyclin D1 expression to promote cell-cycle progression', Oncogene, vol. 40, no. 30, pp. 4872-4883.
Thakar, T & Moldovan, GL 2021, 'The emerging determinants of replication fork stability', Nucleic acids research, vol. 49, no. 13, pp. 7224-7238.
Datta, A, Biswas, K, Sommers, JA, Thompson, H, Awate, S, Nicolae, CM, Thakar, T, Moldovan, GL, Shoemaker, RH, Sharan, SK & Brosh, RM 2021, 'WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells', Nature communications, vol. 12, no. 1, 6561.


Schleicher, EM, Dhoonmoon, A, Jackson, LM, Clements, KE, Stump, CL, Nicolae, CM & Moldovan, GL 2020, 'Dual genome-wide CRISPR knockout and CRISPR activation screens identify mechanisms that regulate the resistance to multiple ATR inhibitors', PLoS genetics, vol. 16, no. 11, e1009176.
Awate, S, Sommers, JA, Datta, A, Nayak, S, Bellani, MA, Yang, O, Dunn, CA, Nicolae, CM, Moldovan, GL, Seidman, MM, Cantor, SB & Brosh, RM 2020, 'FANCJ compensates for RAP80 deficiency and suppresses genomic instability induced by interstrand cross-links', Nucleic acids research, vol. 48, no. 16, pp. 9161-9180.
Dhoonmoon, A, Schleicher, EM, Clements, KE, Nicolae, CM & Moldovan, GL 2020, 'Genome-wide CRISPR synthetic lethality screen identifies a role for the ADP-ribosyltransferase PARP14 in DNA replication dynamics controlled by ATR', Nucleic acids research, vol. 48, no. 13, pp. 7252-7264.
Clements, KE, Schleicher, EM, Thakar, T, Hale, A, Dhoonmoon, A, Tolman, NJ, Sharma, A, Liang, X, Imamura Kawasawa, Y, Nicolae, CM, Wang, HG, De, S & Moldovan, GL 2020, 'Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens', Nature communications, vol. 11, no. 1, 6118.
Thakar, T, Leung, W, Nicolae, CM, Clements, KE, Shen, B, Bielinsky, AK & Moldovan, GL 2020, 'Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly', Nature communications, vol. 11, no. 1, 2147.