Alberto Ciccia, PhD
Alberto Ciccia is an Associate 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/. A video on Dr. Ciccia's laboratory can be found at https://vimeo.com/269946053.
- Associate Professor of Genetics and Development
Credentials & Experience
Education & Training
- PhD, University College London
- Fellowship: Harvard Medical School
Honors & Awards
2008 - EMBO Long-Term Fellowship
2015 - Breast Cancer Alliance Young Investigator Award
2016 - Ovarian Cancer Research Fund Liz Tilberis Award
2016 - Susan G. Komen Career Catalyst Research Award
2018 - Schaefer Research Scholar Award
2018 - Irma T. Hirschl Award
2018 - Pershing Square Sohn Prize
- Breast and ovarian cancer
- Genome editing
- Maintenance of genome stability
1. CRISPR-based genome editing through the lens of DNA repair. Nambiar, T.S., Baudrier, L., Billon, P., and Ciccia, A. (2022). Mol. Cell 82(2), 348-388
2. Towards a CRISPeR understanding of homologous recombination with high-throughput functional genomics. Hayward, S.B., and Ciccia, A. (2021). Curr. Opin. Genet. Dev. 71, 171-181.
3. REV1-Polζ maintains the viability of homologous recombination-deficient cancer cells through mutagenic repair of PRIMPOL-dependent ssDNA gaps. Taglialatela, A., Leuzzi, G., Sannino, V., Cuella-Martin, R., Huang, J.W., Wu-Baer, F., Baer, R., Costanzo, V., and Ciccia, A. (2021). Mol. Cell 81(19), 4008-4025.
4. Functional interrogation of DNA damage response variants with base editing screens. Cuella-Martin, R., Hayward, S.B., Fan, X., Chen, X., Huang, J.W., Taglialatela, A., Leuzzi, G., Zhao, J., Rabadan, R., Lu, C., Shen, Y., and Ciccia, A. (2021). Cell, 184(4), 1081-1097.
5. MCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage. Huang, J.W., Acharya, A., Taglialatela, A., Nambiar, T.S., Cuella-Martin, R., Leuzzi, G., Hayward, S.B., Joseph, S.A., Brunette, G.J., Anand, R., Soni, R.K., Clark, N.L., Bernstein, K.A., Cejka, P., and Ciccia, A. (2020). Nature Comm.,11, 2948
6. Stimulation of CRISPR-mediated homology-directed repair by an engineered RAD18 variant. Nambiar, T.S., Billon, P., Diedenhofen, G., Hayward, S.B., Taglialatela, A., Cai, K., Huang, J.W., Leuzzi, G Cuella-Martin, R., Palacios, A., Gupta, A., Egli, D., and Ciccia, A. (2019). Nature Comm. 10, 3395.
7. The BRCT domains of the BRCA1 and BARD1 tumor suppressors differentially regulate homology-directed repair and stalled fork protection. Billing, D., Horiguchi, M., Wu-Baer, F., Taglialatela, A., Leuzzi, G., Alvarez, S., Jiang, W., Zha, S., Szabolcs, M., Lin, C.-S., Ciccia, A., and Baer, R. (2018). Mol. Cell 72(1), 127-139.
8. Restoration of replication fork stability in BRCA1- and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers. 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). Mol. Cell 68(2), 414-430.
9. CRISPR-mediated base editing enables efficient disruption of eukaryotic genes through induction of STOP codons. Billon, P., Bryant, E.E., Joseph, S.A., Nambiar, T.S., Hayward, S.B., Rothstein, R., Ciccia, A. (2017). Mol. Cell 67(6), 1068-1079.
10. Replication fork slowing and reversal upon DNA damage require PCNA polyubiquitination and ZRANB3 DNA translocase activity. 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). Mol. Cell 67(5), 882-890.
11. SMARCAL1-mediated fork reversal triggers MRE11-dependent degradation of nascent DNA in the absence of BRCA2 and stable RAD51 nucleofilaments. Kolinjivadi, A.M., Sannino, V., De Antoni, A., Zadorozhny, K., Kilkenny, M., Techer, H., Baldi, G., Shen, R., Ciccia, A., Pellegrini, L., Krejci, L., Costanzo, V. (2017). Mol. Cell 67(5), 867-881.
12. Stressing out about RAD52. Ciccia, A.* and Symington, L.S.* (2016). Mol. Cell 64(6), 1017-1019. *Corresponding authors
13. Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response. Ciccia, A.*, Huang, J.W., Izhar, L., Sowa, M.E., Harper, J.W., and Elledge, S.J.* (2014). Proc. Natl. Acad. Sci U S A 111, 18631-18636. *Corresponding authors
14. Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. 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). Mol. Cell 47(3), 396-409.
15. The DNA damage response: making it safe to play with knives. Ciccia, A., and Elledge, S.J. (2010). Mol. Cell 40(2) 179-204.
16. The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart.Ciccia, A., Bredemeyer, A.L., Sowa, M.E., Terret, M.E., Jallepalli, P.V., Harper, J.W., and Elledge, S.J. (2009). Genes Dev. 23(20), 2415-2425.