Genetics and Development
Columbia University Medical Center
Our research focuses on the cellular processes that maintain genome integrity to prevent cancer development. Specifically, we employ genetic and biochemical approaches to determine how defects in the BRCA1 and BRCA2 genes cause genome instability and predispose to breast and ovarian cancer. Our goal is to elucidate the molecular events that cause breast and ovarian cancer and develop novel targeted strategies to prevent and treat these tumors.
Alberto Ciccia received his Ph.D. from the London Research Institute, where he worked in the laboratory of Dr. Stephen West, and conducted his postdoctoral studies in the laboratory of Dr. Stephen Elledge at Harvard Medical School. Over the course of these studies, Dr. Ciccia identified and characterized five novel DNA repair genes that maintain genome stability in mammalian cells. In 2014, Dr. Ciccia was appointed Assistant Professor in the Department of Genetics and Development and the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center. Dr. Ciccia’s laboratory investigates the mechanisms by which the DNA repair genes BRCA1 and BRCA2 suppress breast and ovarian cancer. In addition, his laboratory studies the pathways that repair DNA lesions induced by genome editing technologies. Dr. Ciccia is recipient of numerous awards, including the Breast Cancer Alliance Young Investigator Award, the Susan G. Komen Career Catalyst Research Award, the Ovarian Cancer Research Fund Alliance Liz Tilberis Early Career Award, the Schaefer Research Scholar Award and the Irma T. Hirschl Career Scientist Award.
Regulation of genome stability and innate immunity in breast cancer
Mutations of the BRCA1 gene have been implicated in both familial and sporadic cases of breast and ovarian cancer. BRCA1 suppresses tumor development by preserving genome integrity, and thereby preventing the accumulation of genetic lesions that promote uncontrolled cellular growth and tumor formation. To preserve genome integrity, BRCA1 repairs DNA breaks and protects DNA replication forks, fragile DNA structures that are susceptible to degradation. Recent studies have shown that, because of their unstable genomic DNA, BRCA1-mutant breast cancer cells accumulate DNA fragments outside of the nucleus, the cellular compartment that contains the genome. Non-nuclear DNA fragments can lead to the activation of the innate immune response, a cellular pathway that induces the production of inflammatory signals and the activation of molecules that protect tumor cells from killing by white blood cells. It remains, however, to be determined how BRCA1 suppresses the innate immune response.
“The Pershing Square Sohn Prize will provide my laboratory with the freedom and support to conduct highly multidisciplinary studies for the development of novel therapies against breast and ovarian cancer. As a recipient of this prestigious award, I feel honored to join a vibrant community composed of highly accomplished young investigators and future leaders in cancer research.”
In our recent work we identified a DNA replication factor, known as SMARCAL1, that causes genomic instability, generation of non-nuclear DNA fragments and activation of markers of the innate immune response in BRCA1-mutant breast cancer cells. Based on these observations, we propose 1) to examine how SMARCAL1 activates the innate immune response in BRCA1-mutant breast cells and 2) to determine the contribution of this cellular mechanism to the development of BRCA1-mutant breast tumors. These studies could lead to the development of new therapies against BRCA1-mutant tumors.
“Innovation is the engine of science. It drives research into unexpected directions leading to breakthrough discoveries.”