Paul R. Andreassen, PhD

I have had a long-standing interest in cellular mechanisms which maintain genome stability, including the mitotic and DNA damage responses/DNA repair processes that prevent aneuploidy/polyploidy and structural alterations of chromosomes, respectively. Notably, many of the factors associated with DNA damage responses are tumor suppressors.

I joined the Cincinnati Children’s community in 2004. Current research in my lab is centered on Fanconi anemia (FA), a pediatric chromosome instability syndrome that is caused by mutations, mainly biallelic, in any one of 23 genes. FA is typified by congenital anomalies, progressive bone marrow failure, and a predisposition to various types of cancer. We have had a particular focus on FANCD2, which is monoubiquitinated by the FA core complex that contains nine other FA proteins. We are also interested in a subset of proteins, such as BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN, which are encoded by FA genes that confer an increased risk of breast and ovarian cancer via heterozygous mutations. Taken together, this work, based on molecular and cellular biological, biochemical and genetic approaches, has helped define the regulation and function, and partners, of proteins involved in repairing DNA interstrand crosslinks (ICLs) and DNA double-strand breaks (DSBs). One key goal of our studies is to provide insights that help develop better treatments for FA patients, as well as cancer patients in the general population.

Another current focus of the lab is on the ATM protein kinase, which recruits DNA repair proteins to DSBs. Related to this, to aid in classifying their pathogenicity, we recently developed the first validated and calibrated assay system to functionally characterize variants identified in hereditary cancer and ataxia-telangiectasia (A-T) patients. We are also studying mechanisms of ATM activation and function in response to DSBs and oxidative stress.