logo
title

Alberto  Ciccia
Alberto Ciccia
Assistant Professor


Address: 1130 St. Nicholas Avenue ICRC Room 309A New York NY 10032
Phone: 212-851-4896
Fax:
E-mail:

ac3685@cumc.columbia.edu

Education and Training:
Ph.D. 2006, London Research Institute, University College London
Postdoctoral Fellowship 2007-2013, Harvard Medical School
Affiliations:
bullet  Ciccia laboratory


bullet  Department of Genetics and Development
bullet  Herbert Irving Comprehensive Cancer Center
Training Activities:
bullet  Department of Genetics and Development


bullet  Integrated Program in Cellular, Molecular and Biophysical Studies
Research Summary:
(800 words, max)
The DNA damage response network in cancer and genetic disorders
Current Research:
The faithful conservation of genomic information is an essential process for cell survival. Every day more than 10^5 DNA lesions are generated in each cell of our body as a consequence of DNA damage either spontaneously induced during cellular metabolism (e.g. ROS-induced DNA lesions, DNA decay, DNA replication errors) or caused by environmental agents, such as UV radiation (e.g. sunlight), ionizing radiation (e.g. radiotherapy, X-rays, cosmic radiation, nuclear power) and chemical agents (e.g. chemotherapy, tobacco smoking). In addition, breaks of genomic DNA are formed during immune development and gametogenesis.

To maintain genomic integrity, the signal transduction pathway of the DNA Damage Response (DDR) is activated following DNA damage. The DDR promotes genomic stability by regulating a large network of cellular activities, ranging from DNA replication and repair to transcription, RNA splicing and metabolism. The DDR plays a critical role in human disease. Indeed, mutations in a great number of 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.

To understand the role of the DDR network in human health and disease, our laboratory focuses on the following major lines of investigation:

1) Characterization of the molecular mechanisms that maintain genomic integrity after DNA damage.
Our laboratory is particularly interested in dissecting the molecular mechanisms that ensure accurate DNA replication after DNA damage. Using proteomic and bioinformatic methods we have previously identified and characterized 5 novel DDR factors that maintain genomic integrity during DNA replication: the MUS81 endonuclease subunits EME1 and EME2, the Fanconi anemia associated protein FAAP24, the Schimke immuno-osseous dysplasia (SIOD) protein SMARCAL1 and its related factor ZRANB3. To have a complete understanding of the DDR, we have performed large proteomic analyses of the DDR network after DNA damage. We are currently conducting biochemical and genetic studies to characterize additional new DDR factors that operate during DNA replication and elucidate the molecular machinery that preserves the integrity of DNA replication forks after DNA damage.

2) Definition of the DNA damage response pathways defective in genetic disorders and cancer.
Maintenance of replication fork integrity is essential to prevent genetic diseases and cancer. We have previously shown that the SIOD disorder, a heterogeneous recessive disease that displays growth and developmental abnormalities and cancer predisposition, is characterized by defective cellular proliferation due to replication fork damage. We are now conducting human genetic studies and developing mouse models to define the role of SMARCAL1 and other DDR factors that maintain replication fork integrity in mammalian development and tumor suppression.

We are currently looking for Ph.D. students and postdoctoral fellows interested in joining our laboratory.
Publications:
(6 max)
1. 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

2. 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

3. Ciccia, A., and Elledge, S.J.: (2010) The DNA damage response: making it safe to play with knives.  Mol. Cell 40(2): 179-204

4. 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

5. Ciccia, A., McDonald, N., and West, S.C. : (2008) Structural and functional relationships of the XPF/MUS81 family of proteins.  Annu. Rev. Biochem. 77: 259-287

6. Ciccia, A., Ling, C., Coulthard, R., Yan, Z., Xue, Y., Meetei, A.R., Laghmani el, H., Joenje, H., McDonald, N., de Winter, J.P., Wang, W., and West, S.C.: (2007) Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM.  Mol. Cell 25(3): 331-343

URL for lab page:
 http://www.ciccialab.com/

top

footer