Robert W. Mason
Head of Clinical Biochemistry Laboratory
Nemours Biomedical Research
Alfred I duPont Hospital for Children
1600 Rockland Road
Wilmington, DE 19803
Phone: (302) 651-6885
Fax: (302) 651 6767
PhD, Biochemistry, Leeds University, U.K., 1981
B.Sc, Biochemistry, Bath University, U.K., 1977
The focus of the Clinical Biochemistry Laboratory headed by Robert W. Mason, Ph.D. is on defining biological roles of proteases in growth and development of both normal and cancerous tissues. The overall philosophy of the lab is to take rigorous biochemical approaches into cellular systems to identify important functions of individual proteases. Two major projects are being pursued, one to examine roles that proteases play in cancer and the other to determine the roles of proteases in placental function.
The cancer project currently focuses on neuroblastoma, a cancer of childhood. We have discovered that inhibition of two proteases, cathepsins B and L, induces apoptosis of neuroblastoma cells such that cells die within 3 days of treatment. This is unique to neuroblastoma; other cells grow less aggressively in the presence of the inhibitors but do not die. Inhibition of only one of these enzymes fails to kill neuroblastoma cells, indicating that the enzymes have overlapping functions in tumor cell proliferation and survival. We are developing animal models of neuroblastoma to determine the efficacy protease inhibition to controlling cancer progression. This preclinical study is complemented by a proteomic study to identify the mechanism by which protease inhibition leads to apoptosis. Our working hypothesis is that protease inhibition increases levels of receptor/ligand complexes that induce terminal differentiation and subsequent apoptosis of neuroblastoma cells.
We are continuing work on a family of proteolytic enzymes that we found to be exclusively expressed in rodent placenta. Dysregulation of the activity human orthologs these proteases can lead to preeclampsia. The human enzymes appear to have multiple functions in many tissues, but gene duplications in rodents have led to the evolution of more specific proteases. We have developed proteomic protocols to identify placental substrate proteins for these enzymes with the goal of identifying proteolytic pathways in placenta that are critical to human embryonic development. In this project we use combinatorial libraries of substrates and inhibitors to determine the specificity of recombinant enzymes, examine the regulation of expression of the enzymes in cells and tissues, and develop cellular techniques that regulate expression of the proteases to define their function.
Dr Mason first encountered the field of proteolytic enzymes as a post-doctoral scientist in Bristol, U.K. He developed his expertise in lysosomal proteases with Alan Barrett in Cambridge, U.K. before setting up his own lab in the Department of Biochemistry at Virginia Tech. He came to the Alfred I duPont Hospital for Children in 1994.