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Research | 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
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SCHOOL OF MEDICINE
