Rubin Lab
We are interested in the mechanisms of brain tumorigenesis during early childhood. The pioneering work of Armitage and Doll and Knudson and Weinberg has helped us understand multistage oncogenesis and the increased risk of cancer in familial predisposition syndromes or with advanced age. These studies, however, do not provide an immediate explanation for the high rate of sporadic brain tumors that occurs in children under 4 years of age.
During the pediatric years (birth-age 21), the peak incidence of brain tumors (3.8 cases/100,000 children) occurs during the first 4 years of life. During this time, tumors arise from virtually every cellular lineage in the growing brain. The rate of brain tumor formation subsequently declines to a lifetime nadir during adolescence (1.5 cases/100,000) coincident with the emergence of a more adult pattern of brain tumors: one that is primarily restricted to tumors of glial origin. An incidence of 3.8 cases/100,000 is not reached again until the 5th decade of life, but the histological diversity of early brain tumors does not occur again. These observations suggest that the mechanisms of brain tumorigenesis are different early in life as compared to later in life.
The temporal relationship between the peak of pediatric brain tumors and the period of most rapid brain growth strongly suggests that early brain tumorigenesis is a consequence of normal brain development. We hypothesized that factors essential for patterning normal brain development actively stimulate oncogenesis resulting in a peak of tumor formation that is coincident with the period of most rapid brain growth. These studies identified the chemokine CXCL12 as one candidate brain-derived factor and have supported the conclusion that CXCL12 and its receptor CXCR4 are important regulators of brain tumor growth. They further identified that antagonism of CXCR4 signaling exerts a significant anti-brain tumor effect. We are currently working to define the molecular basis for CXCR4-induced brain tumor growth and are especially focused on dysregulation of CXCR4-mediated cAMP suppression in this process.
Contact Information
Rubin_J@kids.wustl.edu
Rubin Lab
We are interested in the mechanisms of brain tumorigenesis during early childhood. The pioneering work of Armitage and Doll and Knudson and Weinberg has helped us understand multistage oncogenesis and the increased risk of cancer in familial predisposition syndromes or with advanced age. These studies, however, do not provide an immediate explanation for the high rate of sporadic brain tumors that occurs in children under 4 years of age.
During the pediatric years (birth-age 21), the peak incidence of brain tumors (3.8 cases/100,000 children) occurs during the first 4 years of life. During this time, tumors arise from virtually every cellular lineage in the growing brain. The rate of brain tumor formation subsequently declines to a lifetime nadir during adolescence (1.5 cases/100,000) coincident with the emergence of a more adult pattern of brain tumors: one that is primarily restricted to tumors of glial origin. An incidence of 3.8 cases/100,000 is not reached again until the 5th decade of life, but the histological diversity of early brain tumors does not occur again. These observations suggest that the mechanisms of brain tumorigenesis are different early in life as compared to later in life.
The temporal relationship between the peak of pediatric brain tumors and the period of most rapid brain growth strongly suggests that early brain tumorigenesis is a consequence of normal brain development. We hypothesized that factors essential for patterning normal brain development actively stimulate oncogenesis resulting in a peak of tumor formation that is coincident with the period of most rapid brain growth. These studies identified the chemokine CXCL12 as one candidate brain-derived factor and have supported the conclusion that CXCL12 and its receptor CXCR4 are important regulators of brain tumor growth. They further identified that antagonism of CXCR4 signaling exerts a significant anti-brain tumor effect. We are currently working to define the molecular basis for CXCR4-induced brain tumor growth and are especially focused on dysregulation of CXCR4-mediated cAMP suppression in this process.
Contact Information
Rubin_J@kids.wustl.edu