Our laboratory focuses on the roles of specific
signal transduction pathways in the biology of malignant
brain tumors. Current therapies for malignant brain
tumors include ionizing radiation and chemotherapies
that damage DNA or the mitotic spindle in non-specific
fashions. Novel cancer therapies in development target
biologic processes that promote cancer formation
and maintenance. Tumor cell invasion and angiogenesis
are critical tumor behaviors that contribute to the
overwhelming lethality of malignant gliomas. We are
currently investigating two interrelated molecular
contributors to invasion and angiogenesis – transforming
growth factor-beta (TGF-beta) and secreted protein
acidic and rich in cysteine (SPARC). TGF-beta can
function as both a tumor suppressor and a tumor enhancer.
The molecular switch underlying the shift in cellular
response to TGF-beta remains unclear. We are currently
defining interactions between TGF-beta signaling
and other oncogenic pathways that alter phenotypic
responses to TGF-beta. Additional studies involve
defining intracellular pathways of a TGF-beta-induced
gene product, SPARC, that lead to tumor cell survival
and resistance to apoptosis. Finally, our newest
area of study focuses on the roles of cancer stem
cells in therapeutic resistance. Specific cellular
signaling processes are differentially activated
in cancer stem cells to contribute to resistance
to genotoxic insults. We are currently using experimental
cancer therapies to disrupt each of these mechanisms
to lay the foundation for new clinical trials that
can be directly translated into studies in the Brain
Tumor Center at Duke.
