The Kupfer Lab works on the relationship of genomic instability and the propensity towards development of cancer. Specifically, we focus on the genetic syndrome Fanconi anemia (FA). Interestingly, children with FA are born with congenital anomalies and develop aplastic anemia and an assortment of leukemias and other cancers. FA serves as a paradigm where the disciplines of development, genetics, and molecular oncology come together. Like other cancer susceptibility syndromes, such as ataxia telangiectasia and xeroderma pigmentosum, FA patients exhibit a unique hypersensitivity to DNA crosslinking agents, which is the key to the biology of FA. Unlike the other syndromes, exceedingly little is known about FA. Thirteen complementation groups have been elucidated, with all exhibiting similar phenotypic characteristics, suggesting an interrelationship of proteins in a complex or in a linear pathway.
To date, 23 genes have been cloned, but the encoded proteins are of uncertain function. Excitingly, BRCA1 and BRCA2 are bona fide genes as well. Recent work, including our own, has implicated a role for FA in homologous recombinatorial repair. Interestingly, the FA pathway and breast cancer biology have significant overlap, as at least 5 FA genes are bona fide familial breast cancer genes.
Our work has focused on:
protein-protein interactions of FA proteins
signal transduction pathway of FA proteins
biochemistry of FA protein function
The Kupfer laboratory is part of the wider community of researchers involved in DNA repair. We formally collaborate with Dr Patrick Sung, a DNA repair enzymologist at UT-San Antonio, focused on DNA repair. We interact with Dr Stephanie Halene, Yale, on a mouse model of FA. We are also working with Dr Barbara Burtness at Yale on adapting FA biology for the improvement of cancer therapy.