Associate Professor, Center for Genetic Medicine; Feinberg School of Medicine
Tumor Invasion, Metastasis & Angiogenesis
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Dr. Beitel’s laboratory uses genetic, molecular and biochemical approaches with the model organism Drosophila melanogaster to investigate three areas of tumor progression: the mechanisms of vascular tube-size control, cell-cell junction organization and cellular responses to elevated CO2 levels.
Vascular tube-size control and cell-cell junction organization have important implications for cancer because the ability to regulate vascular tube size could lead to a new class of anti-angiogenic based anti-cancer therapies and because many cell junction components have functions in cell polarity and growth control that are specifically disrupted in cancerous cells. Work in the Beitel lab has demontrated that a particular cell-cell junction, which contains known tumor suppressor proteins, has a critical role in controlling the sizes of the tubes that delivers oxygen throughout the Drosophila embryo. The lab has identified several new components of this junction and have shown that this junction is more closely related to human cell-cell junctions than was previous believed. Recently we have identified a new function for one of the first identified oncogenes, the tyrosine kinase Src. We and our collaborators have shown that in flies and mammals, Src is required to control the orientation of cell growth. Without Src activity, cells grow circumferentially rather the along the legnth of the tubes, making the tubes abnormally wide and short. Current work is aimed at understanding the molecular mechanisms by which Src and junctional complexes control tube size.
The biology of evelated CO2 is important to cancer because preliminary evidence shows that elevated CO2 levels that might occur in solid tumors, suppress immune functions that should block tumor growth. We are currently working to define the cellular pathways that sense and regulated the effects of elelvated CO2 (hypercapnia).
particular protein-protein interaction domains that are prevalent among tumor suppressor and cell signaling proteins. These screens will be done for both the human and Drosophila proteomes, with the experimental manipulability of Drosophila allowing for rapid in vivo validation of conserved interactions. Confirmed interactions will be further analyzed in vertebrate models. Understanding these networks should identify multiple therapeutic intervention strategies to limit the growth of tumor cells.