Craig Bassing Laboratory
Led by Craig Bassing, PhD, researchers in the Craig Bassing Laboratory are studying the contributions of mutations in cellular DNA repair machinery and normal lymphocyte development to oncogenic mechanisms in childhood lymphomas and leukemias. The primary long-term goal of the work in this lab is to design, develop and test novel treatments for pediatric cancers that are more effective and less toxic than current clinical therapies.
Ongoing research in the Bassing laboratory has resulted in the creation of a unique transgenic mouse model to study the effects of somatic ATM mutations and chromosomal TCR germline translocations on the development of T-ALL. The use of this model revealed that acquired ATM mutations predisposed mice to develop T-ALL that was dependent upon Cyclin D3, a protein that drives immature T cell proliferation. Also, germline TCR translocations that occurred in ATM-deficient transgenic mice resulted in deletion of BCl1 1b suppressor gene that caused the mice to develop human-like T-ALL disease.
Other studies in the Bassing laboratory led to the development of a transgenic mouse model that was used to demonstrate that somatic inactivation of the TP53 tumor suppressor gene predisposed mice to thymic lymphomas with translocations. This finding suggested that normal TP53 gene responses to DNA damage are critical for preventing malignant transformation of T and B lymphocytes.
Both transgenic mouse models will be used in future studies to identify novel cellular targets and to develop new cancer therapies to treat pediatric lymphomas and T-ALL with either ATM or TP53 deficiencies.