The Vander Kooi lab focuses on understanding the basic mechanisms by which secreted growth factors regulate and coordinate cell signaling in complex multicellular organisms. The lab also studies how these natural signaling pathways become perturbed and lead to human diseases.
The lab’s specific interest centers on the essential human cell surface receptor neuropilin. Neuropilin is a conserved bi-functional mammalian cell surface receptor. Neuropilin has fundamental biomedical importance since it is essential to two distinct biological processes, angiogenesis and axon guidance. During angiogenesis, neuropilin binds VEGF and functions as a co-receptor for the VEGF-R receptor tyrosine kinases. During neural development, neuropilin binds semaphorin and functions as a co-receptor for members of the plexin and L1CAM family of receptors. The Vander Kooi lab seeks to understand neuropilin ligand binding, specificity, and receptor activation. Fundamentally, the lab’s goal will be to answer the following questions: How does neuropilin activate and regulate VEGF dependent angiogenesis, and how does it function in semaphorin dependent axon guidance?
Neuropilin and tumor angiogenesis
In additions to its normal roles, neuropilin also functions in tumor angiogenesis. Neuropilin expression is observed in tumor vasculature, and overexpression promotes tumorigenesis in vivo for a variety of solid tumors including those of the pituitary, prostate, breast, and colon. Recent evidence has also demonstrated a role for neuropilin in hematological malignancies where neuropilin overexpression is observed in both multiple myeloma and acute myeloid leukemia. In contrast, a soluble splice form containing only the ligand binding region of the extracellular domain of neuropilin inhibits tumorigenesis. Additionally, a number of peptides that block VEGF binding to neuropilin exhibit anti-tumorigenic activity. Strategies to inhibit neuropilin activity are being developed as potential antitumor therapies. The lab seeks to define and improve mechanisms of inhibiting the neuropilin signaling pathway.