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Personal profile

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.

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Proliferating Cell Nuclear Antigen Medicine & Life Sciences
DNA Repair Medicine & Life Sciences
Genomic Instability Medicine & Life Sciences
DNA Damage Medicine & Life Sciences
DNA Replication Medicine & Life Sciences
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DNA-Directed DNA Polymerase Medicine & Life Sciences
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Projects 2016 2021

Adenosine Diphosphate
Radiation
Recombinational DNA Repair
Double-Stranded DNA Breaks
DNA Damage

Research Output 2002 2019

  • 4226 Citations
  • 15 h-Index
  • 25 Article
  • 4 Review article
  • 3 Comment/debate
  • 3 Short survey

Activation of Wnt signaling promotes olaparib resistant ovarian cancer

Yamamoto, T. M., McMellen, A., Watson, Z. L., Aguilera, J., Ferguson, R., Nurmemmedov, E., Thakar, T., Moldovan, G-L., Kim, H., Cittelly, D. M., Joglar, A. M., Brennecke, E. P., Wilson, H., Behbakht, K., Sikora, M. J. & Bitler, B. G., Oct 1 2019, In : Molecular Carcinogenesis. 58, 10, p. 1770-1782 13 p.

Research output: Contribution to journalArticle

Ovarian Neoplasms
Carcinoma
Ovarian Diseases
Recombinational DNA Repair
Cell Line

Error-prone replication of a 5-formylcytosine-mediated DNA-peptide cross-link in human cells

Naldiga, S., Ji, S., Thomforde, J., Nicolae, C., Lee, M., Zhang, Z., Moldovan, G-L., Tretyakova, N. Y. & Basu, A. K., Jan 1 2019, In : Journal of Biological Chemistry. 294, 27, p. 10619-10627 9 p.

Research output: Contribution to journalArticle

Cells
Peptides
Mutation
DNA
Plasmids

Heterozygous RNF13 Gain-of-Function Variants Are Associated with Congenital Microcephaly, Epileptic Encephalopathy, Blindness, and Failure to Thrive

Edvardson, S., Nicolae, C., Noh, G. J., Burton, J. E., Punzi, G., Shaag, A., Bischetsrieder, J., De Grassi, A., Pierri, C. L., Elpeleg, O. & Moldovan, G-L., Jan 3 2019, In : American Journal of Human Genetics. 104, 1, p. 179-185 7 p.

Research output: Contribution to journalArticle

Failure to Thrive
Microcephaly
Brain Diseases
Blindness
Protein Unfolding
7 Citations (Scopus)

Mechanisms of DNA damage tolerance: post-translational regulation of PCNA

Leung, W., Baxley, R. M., Moldovan, G-L. & Bielinsky, A. K., Jan 1 2019, In : Genes. 10, 1, 10.

Research output: Contribution to journalReview article

Proliferating Cell Nuclear Antigen
DNA Damage
Post Translational Protein Processing
Ubiquitin
Genetic Recombination

PARI (PARPBP) suppresses replication stress-induced myeloid differentiation in leukemia cells

Nicolae, C., O’Connor, M. J., Schleicher, E. M., Song, C., Gowda, R., Robertson, G., Dovat, S. & Moldovan, G-L., Jul 4 2019, In : Oncogene. 38, 27, p. 5530-5540 11 p.

Research output: Contribution to journalArticle

Myeloid Leukemia
Leukemia
DNA Damage
Myeloid Cells
Differentiation Antigens