Craig Vander Kooi
Assistant Professor
B.S. Wheaton College
M.S. University of Michigan
Ph.D. Vanderbilt University
Postdoctoral Fellowship Johns Hopkins University
craig.vanderkooi@uky.edu

Research Interests: 

Our lab focuses on understanding the basic mechanisms by which secreted growth factors regulate and coordinate cell signaling in complex multicellular organisms.  We also study how these natural signaling pathways become perturbed and lead to human diseases. 

Neuropilin signaling 

Our 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.   We seek to understand neuropilin ligand binding, specificity, and receptor activation.  Fundamentally, our 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.  Our lab seeks to define and improve mechanisms of inhibiting the neuropilin signaling pathway. 
 

Recent Publications 

1) Vander Kooi C.W., Jusino M.A., Perman B., Neau D.B., Bellamy H.D., & Leahy D.J. (2007)  Structural basis for ligand and heparin binding to neuropilin B domains. Proc Natl Acad Sci USA. 104, 6152-7. 

2) Dattilo B.M., Fritz G., Leclerc E., Vander Kooi C.W., Heizmann C.W., & Chazin W.J. (2007) The extracellular region of the receptor for advanced glycation end products Is  composed of two independent structural Units.  Biochemistry 46, 6957-6970. 

3) Vander Kooi C.W., Ohi M.D., Oldham M.L., Newcomer M.A., Gould K.L., & Chazin W.J. (2006) The Prp19 U-box crystal structure suggests a common dimeric architecture for a class of oligomeric E3 ubiquitin ligases. Biochemistry 45, 121-30. 

4) Vander Kooi B.T., Onuma H., Oeser J.K., Svitek C.A., Allen S.R., Vander Kooi C.W., Chazin W.J., & O'Brien R.M. (2005) The glucose-6-phosphatase catalytic subunit gene promoter contains both positive and negative glucocorticoid response elements. Mol Endocrinol. 19, 3001-22. 

5) Malmendal A., Vander Kooi C.W., Nielsen N.C. & Chazin W.J. (2005) Calcium-modulated S100 protein-phospholipid interactions. An NMR study of calbindin D9k and DPC. Biochemistry 44, 6502-6512. 

6) Ohi M.D., Vander Kooi C.W., Rosenberg J.A., Ren L., Chazin W.J., Walz T., & Gould K.L. (2005) Structural and functional analysis of the essential pre-mRNA splicing factor Prp19p. Mol. Cell.  Biol. 25, 451-460. 

7) Ohi M.D.*, Vander Kooi C.W.*, Rosenberg J.A., Chazin W.J., & Gould K.L. (2003) Structural insights into the U-box, a domain associated with multi-ubiquitination. Nat. Struct. Biol. 10, 250-255.