Alberto Ciccia, PhD
Alberto Ciccia is an Assistant Professor in the Department of Genetics and Development and the Herbert Irving Comprehensive Cancer Center. Dr. Ciccia obtained his Ph.D. from the London Research Institute at University College London, where he worked in the laboratory of Dr. Stephen West. In 2007, he joined as a postdoctoral fellow the laboratory of Dr. Stephen Elledge at Harvard Medical School. In 2014, he was appointed Assistant Professor at Columbia University Medical Center.
Dr. Ciccia’s laboratory is interested in elucidating the mechanisms by which the DNA damage response (DDR) operates to maintain genome integrity. The DDR plays a critical role in human disease and mutations in DDR genes cause more than 40 genetic disorders affecting the development of nervous, reproductive and immune systems and predisposing individuals to premature aging and cancer (Ciccia and Elledge, Mol Cell, 2010). During his previous studies, Dr. Ciccia identified and characterized five novel DNA repair factors that prevent the development of cancer and genetic disorders, including the DNA nucleases EME1 and EME2, the Fanconi anemia associated protein FAAP24, the Schimke immuno-osseous dysplasia protein SMARCAL1 and its related factor ZRANB3 (Ciccia et al, Mol Cell, 2007; Ciccia et al, Genes Dev, 2009; Ciccia et al, Mol Cell, 2012). Dr. Ciccia is currently utilizing biochemical and genetic tools to identify novel components of the DDR.
In addition, Dr. Ciccia is investigating the mechanisms by which the DNA repair genes BRCA1 and BRCA2 suppress breast and ovarian cancer. BRCA1 and BRCA2 maintain genome integrity by promoting the repair of DNA double-strand breaks (DSBs) by homologous recombination and by protecting stalled replication forks from degradation. Dr. Ciccia's laboratory has recently discovered that SMARCAL1 and ZRANB3 promote the degradation of stalled forks in BRCA1- and BRCA2-deficient cells, thus causing genomic instability in those cells (Taglialatela, Alvarez et al, Mol Cell, 2017). These studies provide novel mechanistic insights into the processes that cause genome instability in BRCA1- and BRCA2-deficient cells.
Dr. Ciccia’s laboratory is also studying how DNA repair pathways regulate CRISPR-Cas9-mediated gene editing. In a recent study, Dr. Ciccia’s laboratory reported that CRISPR-mediated base editing directly converts four codons (CAA, CAG, CGA and TGG) into STOP codons, thus allowing gene inactivation without DSB formation (Billon, Bryant et al, Mol Cell, 2017). Induction of STOP codons (iSTOP) is compatible with gene disruption studies on a genome-wide scale and can be employed to model cancer-associated nonsense mutations (http://www.ciccialab-database.com/istop). This work establishes iSTOP as an efficient gene disruption technology to investigate eukaryotic gene functions and model human diseases.
Additional information about projects conducted in Dr. Ciccia’s laboratory can be found at http://www.ciccialab.com/.
Taglialatela, A., Alvarez, S., Leuzzi, G., Sannino, V., Ranjha, L., Huang, J.W., Madubata, C., Anand, R., Levy, B., Rabadan, R., Cejka, P., Costanzo, V., and Ciccia, A. (2017). Restoration of replication fork stability in BRCA1- and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers. Mol. Cell 68(2), 414-430.
Billon, P., Bryant, E.E., Joseph, S.A., Nambiar, T.S., Hayward, S.B., Rothstein, R., Ciccia, A. (2017). CRISPR-mediated base editing enables efficient disruption of eukaryotic genes through induction of STOP codons. Mol. Cell 67(6), 1068-1079.
Vujanovic, M., Krietsch, J., Raso, M.C., Terraneo, N., Zellweger, R., Schmid, J.A., Taglialatela, A., Huang, J.W., Holland, C.L., Zwicky, K., Herrador, R., Jacobs, H., Cortez, D., Ciccia, A., Penengo, L., Lopes, M. (2017). Replication fork slowing and reversal upon DNA damage require PCNA polyubiquitination and ZRANB3 DNA translocase activity. Mol. Cell 67(5), 882-890.
Kolinjivadi, A.M., Sannino, V., De Antoni, A., Zadorozhny, K., Kilkenny, M., Técher, H., Baldi, G., Shen, R., Ciccia, A., Pellegrini, L., Krejci, L., Costanzo, V. (2017). SMARCAL1-mediated fork reversal triggers MRE11-dependent degradation of nascent DNA in the absence of BRCA2 and stable RAD51 nucleofilaments. Mol. Cell 67(5), 867-881.
Ciccia, A.* and Symington, L.S.* (2016). Stressing out about RAD52. Mol. Cell 64(6), 1017-1019. *Corresponding authors
Ciccia, A.*, Huang, J.W., Izhar, L., Sowa, M.E., Harper, J.W., and Elledge, S.J.* (2014). Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response. Proc. Natl. Acad. Sci U S A 111, 18631-18636. *Corresponding authors
Ciccia, A., Nimonkar, A.V., Hu, Y., Hajdu, I., Achar, Y.J., Izhar, L., Petit, S.A., Adamson, B., Yoon, J.C., Kowalczykowski, S.C., Livingston, D.M., Haracska, L., and Elledge, S.J. (2012). Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Mol. Cell 47(3), 396-409.
Ciccia, A., and Elledge, S.J. (2010). The DNA damage response: making it safe to play with knives. Mol. Cell 40(2) 179-204.
Ciccia, A., Bredemeyer, A.L., Sowa, M.E., Terret, M.E., Jallepalli, P.V., Harper, J.W., and Elledge, S.J. (2009). The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart. Genes Dev. 23(20), 2415-2425.