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, 15 genes have been cloned, but the encoded proteins bear no resemblance to each other or to any other known proteins. 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 have established a connection with the Sung/Glazer/Sweasy/Sartorelli/Rockwell labs in a program project focused on DNA repair.
Based on our interest in bone marrow failure and genomic instability, we are working on 3 related projects.
Further, we have collected blood from 6 families in which there is a parent and child with Hodkgin lymphoma. We have teamed up with Dr Richard Lifton to apply his cutting edge genome sequencing platform to identify a candidate gene for familial Hodgkin. We have already identified several exciting candidates and are in the process of further evaluation.