Craig William Vander Kooi

Bio / Education: 

B.S. Wheaton College
M.S. University of Michigan
Ph.D. Vanderbilt University
Postdoc Johns Hopkins

Research Description: 

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.


PubMed Publications: 

  • Parker, M.W.;Vander Kooi, C.W. "Plate-Based Assay for Measuring Direct Semaphorin-Neuropilin Interactions." Methods in molecular biology (Clifton, N.J.) 1493, (2017): 73-87. [PubMed Link] | [ Full text ]
  • Gentry, M.S.;Brewer, M.K.;Vander Kooi, C.W. "Structural biology of glucan phosphatases from humans to plants." Current opinion in structural biology 40, (2016): 62-69. [PubMed Link] | [ Full text ]
  • Lu, H.;Cassis, L.A.;Vander Kooi, C.W.;Daugherty, A. "Corrigendum: Structure and functions of angiotensinogen." Hypertension research : official journal of the Japanese Society of Hypertension 39, 11 (2016): 827. [PubMed Link] | [ Full text ]
  • Goel, H.L.;Pursell, B.;Shultz, L.D.;Greiner, D.L.;Brekken, R.A.;Vander Kooi, C.W.;Mercurio, A.M. "P-Rex1 Promotes Resistance to VEGF/VEGFR-Targeted Therapy in Prostate Cancer." Cell reports 14, 9 (2016): 2193-208. [PubMed Link] | [ Full text ]
  • Harris, D.T.;Singh, N.K.;Cai, Q.;Smith, S.N.;Vander Kooi, C.W.;Procko, E.;Kranz, D.M.;Baker, B.M. "An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry." Structure (London, England : 1993) 24, 7 (2016): 1142-54. [PubMed Link] | [ Full text ]
  • Lu, H.;Cassis, L.A.;Kooi, C.W.;Daugherty, A. "Structure and functions of angiotensinogen." Hypertension research : official journal of the Japanese Society of Hypertension 39, 7 (2016): 492-500. [PubMed Link] | [ Full text ]
  • Meekins, D.A.;Vander Kooi, C.W.;Gentry, M.S. "Structural mechanisms of plant glucan phosphatases in starch metabolism." The FEBS journal 283, 13 (2016): 2427-47. [PubMed Link] | [ Full text ]
  • McDonald, N.A.;Takizawa, Y.;Feoktistova, A.;Xu, P.;Ohi, M.D.;Vander Kooi, C.W.;Gould, K.L. "The Tubulation Activity of a Fission Yeast F-BAR Protein Is Dispensable for Its Function in Cytokinesis." Cell reports 14, 3 (2016): 534-46. [PubMed Link] | [ Full text ]
  • Lu, H.;Wu, C.;Howatt, D.A.;Balakrishnan, A.;Moorleghen, J.J.;Chen, X.;Zhao, M.;Graham, M.J.;Mullick, A.E.;Crooke, R.M.;Feldman, D.L.;Cassis, L.A.;Vander Kooi, C.W.;Daugherty, A. "Angiotensinogen Exerts Effects Independent of Angiotensin II." Arteriosclerosis, thrombosis, and vascular biology 36, 2 (2016): 256-65. [PubMed Link] | [ Full text ]
  • Miriyala, S.;Thippakorn, C.;Chaiswing, L.;Xu, Y.;Noel, T.;Tovmasyan, A.;Batinic-Haberle, I.;Vander Kooi, C.W.;Chi, W.;Latif, A.A.;Panchatcharam, M.;Prachayasittikul, V.;Butterfield, D.A.;Vore, M.;Moscow, J.;St Clair, D.K. "Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling." Free radical biology & medicine 91, (2016): 68-80. [PubMed Link] | [ Full text ]
  • Thacker, B.E.;Seamen, E.;Lawrence, R.;Parker, M.W.;Xu, Y.;Liu, J.;Vander Kooi, C.W.;Esko, J.D. "Expanding the 3-O-Sulfate Proteome--Enhanced Binding of Neuropilin-1 to 3-O-Sulfated Heparan Sulfate Modulates Its Activity." ACS chemical biology 11, 4 (2016): 971-80. [PubMed Link] | [ Full text ]
  • Meekins, D.A.;Raththagala, M.;Auger, K.D.;Turner, B.D.;Santelia, D.;Kötting, O.;Gentry, M.S.;Vander Kooi, C.W. "Mechanistic Insights into Glucan Phosphatase Activity against Polyglucan Substrates." The Journal of biological chemistry 290, 38 (2015): 23361-70. [PubMed Link] | [ Full text ]
  • Raththagala, M.;Brewer, M.K.;Parker, M.W.;Sherwood, A.R.;Wong, B.K.;Hsu, S.;Bridges, T.M.;Paasch, B.C.;Hellman, L.M.;Husodo, S.;Meekins, D.A.;Taylor, A.O.;Turner, B.D.;Auger, K.D.;Dukhande, V.V.;Chakravarthy, S.;Sanz, P.;Woods VL, J.;Li, S.;Vander Kooi, C.W.;Gentry, M.S. "Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease." Molecular cell 57, 2 (2015): 261-72. [PubMed Link] | [ Full text ]
  • Guo, H.F.;Vander Kooi, C.W. "Neuropilin Functions as an Essential Cell Surface Receptor." The Journal of biological chemistry 290, 49 (2015): 29120-6. [PubMed Link] | [ Full text ]
  • McDonald, N.A.;Vander Kooi, C.W.;Ohi, M.D.;Gould, K.L. "Oligomerization but Not Membrane Bending Underlies the Function of Certain F-BAR Proteins in Cell Motility and Cytokinesis." Developmental cell 35, 6 (2015): 725-36. [PubMed Link] | [ Full text ]
  • Parker, M.W.;Linkugel, A.D.;Goel, H.L.;Wu, T.;Mercurio, A.M.;Vander Kooi, C.W. "Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a soluble splice form." Structure (London, England : 1993) 23, 4 (2015): 677-87. [PubMed Link] | [ Full text ]
  • Wu, C.;Xu, Y.;Lu, H.;Howatt, D.A.;Balakrishnan, A.;Moorleghen, J.J.;Vander Kooi, C.W.;Cassis, L.A.;Wang, J.A.;Daugherty, A. "Cys18-Cys137 disulfide bond in mouse angiotensinogen does not affect AngII-dependent functions in vivo." Hypertension (Dallas, Tex. : 1979) 65, 4 (2015): 800-5. [PubMed Link] | [ Full text ]
  • Dunlap, T.B.;Guo, H.F.;Cook, E.C.;Holbrook, E.;Rumi-Masante, J.;Lester, T.E.;Colbert, C.L.;Vander Kooi, C.W.;Creamer, T.P. "Stoichiometry of the calcineurin regulatory domain-calmodulin complex." Biochemistry 53, 36 (2014): 5779-90. [PubMed Link] | [ Full text ]
  • Meekins, D.A.;Raththagala, M.;Husodo, S.;White, C.J.;Guo, H.F.;Kötting, O.;Vander Kooi, C.W.;Gentry, M.S. "Phosphoglucan-bound structure of starch phosphatase Starch Excess4 reveals the mechanism for C6 specificity." Proceedings of the National Academy of Sciences of the United States of America 111, 20 (2014): 7272-7. [PubMed Link] | [ Full text ]
  • Parker, M.W.;Vander Kooi, C.W. "Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular endothelial growth factor-C interactions." Analytical biochemistry 453, (2014): 4-6. [PubMed Link] | [ Full text ]
  • Li, X.;Parker, M.W.;Vander Kooi, C.W. "Control of cellular motility by neuropilin-mediated physical interactions." Biomolecular concepts 5, 2 (2014): 157-66. [PubMed Link] | [ Full text ]
  • Pierce, B.G.;Hellman, L.M.;Hossain, M.;Singh, N.K.;Vander Kooi, C.W.;Weng, Z.;Baker, B.M. "Computational design of the affinity and specificity of a therapeutic T cell receptor." PLoS computational biology 10, 2 (2014): e1003478. [PubMed Link] | [ Full text ]
  • Wu, T.;Kooi, C.V.;Shah, P.;Charnigo, R.;Huang, C.;Smyth, S.S.;Morris, A.J. "Integrin-mediated cell surface recruitment of autotaxin promotes persistent directional cell migration." FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28, 2 (2014): 861-70. [PubMed Link] | [ Full text ]
  • Guo, H.F.;Li, X.;Parker, M.W.;Waltenberger, J.;Becker, P.M.;Vander Kooi, C.W. "Mechanistic basis for the potent anti-angiogenic activity of semaphorin 3F." Biochemistry 52, 43 (2013): 7551-8. [PubMed Link] | [ Full text ]
  • Bohnert, K.A.;Grzegorzewska, A.P.;Willet, A.H.;Vander Kooi, C.W.;Kovar, D.R.;Gould, K.L. "SIN-dependent phosphoinhibition of formin multimerization controls fission yeast cytokinesis." Genes & development 27, 19 (2013): 2164-77. [PubMed Link] | [ Full text ]
  • Parker, M.W.;Linkugel, A.D.;Vander Kooi, C.W. "Effect of C-terminal sequence on competitive semaphorin binding to neuropilin-1." Journal of molecular biology 425, 22 (2013): 4405-14. [PubMed Link] | [ Full text ]
  • Meekins, D.A.;Guo, H.F.;Husodo, S.;Paasch, B.C.;Bridges, T.M.;Santelia, D.;Kötting, O.;Vander Kooi, C.W.;Gentry, M.S. "Structure of the Arabidopsis glucan phosphatase like sex four2 reveals a unique mechanism for starch dephosphorylation." The Plant cell 25, 6 (2013): 2302-14. [PubMed Link] | [ Full text ]
  • Zhang, W.;Sviripa, V.;Chen, X.;Shi, J.;Yu, T.;Hamza, A.;Ward, N.D.;Kril, L.M.;Vander Kooi, C.W.;Zhan, C.G.;Evers, B.M.;Watt, D.S.;Liu, C. "Fluorinated N,N-dialkylaminostilbenes repress colon cancer by targeting methionine S-adenosyltransferase 2A." ACS chemical biology 8, 4 (2013): 796-803. [PubMed Link] | [ Full text ]
  • Goel, H.L.;Pursell, B.;Chang, C.;Shaw, L.M.;Mao, J.;Simin, K.;Kumar, P.;Vander Kooi, C.W.;Shultz, L.D.;Greiner, D.L.;Norum, J.H.;Toftgard, R.;Kuperwasser, C.;Mercurio, A.M. "GLI1 regulates a novel neuropilin-2/α6β1 integrin based autocrine pathway that contributes to breast cancer initiation." EMBO molecular medicine 5, 4 (2013): 488-508. [PubMed Link] | [ Full text ]
  • Jeoung, M.;Abdelmoti, L.;Jang, E.R.;Vander Kooi, C.W.;Galperin, E. "Functional Integration of the Conserved Domains of Shoc2 Scaffold." PloS one 8, 6 (2013): e66067. [PubMed Link] | [ Full text ]
  • Vander Kooi, C.W. "Megaprimer method for mutagenesis of DNA." Methods in enzymology 529, (2013): 259-69. [PubMed Link] | [ Full text ]
  • Parker, M.W.;Guo, H.F.;Li, X.;Linkugel, A.D.;Vander Kooi, C.W. "Function of members of the neuropilin family as essential pleiotropic cell surface receptors." Biochemistry 51, 47 (2012): 9437-46. [PubMed Link] | [ Full text ]
  • Parker, M.W.;Xu, P.;Li, X.;Vander Kooi, C.W. "Structural basis for selective vascular endothelial growth factor-A (VEGF-A) binding to neuropilin-1." The Journal of biological chemistry 287, 14 (2012): 11082-9. [PubMed Link] | [ Full text ]
  • Parker, M.W.;Xu, P.;Guo, H.F.;Vander Kooi, C.W. "Mechanism of selective VEGF-A binding by neuropilin-1 reveals a basis for specific ligand inhibition." PloS one 7, 11 (2012): e49177. [PubMed Link] | [ Full text ]
  • Fulkerson, Z.;Wu, T.;Sunkara, M.;Kooi, C.V.;Morris, A.J.;Smyth, S.S. "Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells." The Journal of biological chemistry 286, 40 (2011): 34654-63. [PubMed Link] | [ Full text ]
  • Ren, L.;McLean, J.R.;Hazbun, T.R.;Fields, S.;Vander Kooi, C.;Ohi, M.D.;Gould, K.L. "Systematic two-hybrid and comparative proteomic analyses reveal novel yeast pre-mRNA splicing factors connected to Prp19." PloS one 6, 2 (2011): e16719. [PubMed Link] | [ Full text ]
  • Hausmann, J.;Kamtekar, S.;Christodoulou, E.;Day, J.E.;Wu, T.;Fulkerson, Z.;Albers, H.M.;Meeteren, L.A.;Houben, A.J.;Zeijl, L.;Jansen, S.;Andries, M.;Hall, T.;Pegg, L.E.;Benson, T.E.;Kasiem, M.;Harlos, K.;Kooi, C.W.;Smyth, S.S.;Ovaa, H.;Bollen, M.;Morris, A.J.;Moolenaar, W.H.;Perrakis, A. "Structural basis of substrate discrimination and integrin binding by autotaxin." Nature structural & molecular biology 18, 2 (2011): 198-204. [PubMed Link] | [ Full text ]
  • Parker, M.W.;Hellman, L.M.;Xu, P.;Fried, M.G.;Vander Kooi, C.W. "Furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin." Biochemistry 49, 19 (2010): 4068-75. [PubMed Link] | [ Full text ]
  • Vander Kooi, C.W.;Ren, L.;Xu, P.;Ohi, M.D.;Gould, K.L.;Chazin, W.J. "The Prp19 WD40 domain contains a conserved protein interaction region essential for its function." Structure (London, England : 1993) 18, 5 (2010): 584-93. [PubMed Link] | [ Full text ]
  • Vander Kooi, C.W.;Taylor, A.O.;Pace, R.M.;Meekins, D.A.;Guo, H.F.;Kim, Y.;Gentry, M.S. "Structural basis for the glucan phosphatase activity of Starch Excess4." Proceedings of the National Academy of Sciences of the United States of America 107, 35 (2010): 15379-84. [PubMed Link] | [ Full text ]
  • Merte, J.;Wang, Q.;Vander Kooi, C.W.;Sarsfield, S.;Leahy, D.J.;Kolodkin, A.L.;Ginty, D.D. "A forward genetic screen in mice identifies Sema3A(K108N), which binds to neuropilin-1 but cannot signal." The Journal of neuroscience : the official journal of the Society for Neuroscience 30, 16 (2010): 5767-75. [PubMed Link] | [ Full text ]
  • Bohnert, K.A.;Chen, J.S.;Clifford, D.M.;Vander Kooi, C.W.;Gould, K.L. "A link between aurora kinase and Clp1/Cdc14 regulation uncovered by the identification of a fission yeast borealin-like protein." Molecular biology of the cell 20, 16 (2009): 3646-59. [PubMed Link] | [ Full text ]
  • Mori, M.X.;Vander Kooi, C.W.;Leahy, D.J.;Yue, D.T. "Crystal structure of the CaV2 IQ domain in complex with Ca2+/calmodulin: high-resolution mechanistic implications for channel regulation by Ca2+." Structure (London, England : 1993) 16, 4 (2008): 607-20. [PubMed Link] | [ Full text ]
  • Dattilo, B.M.;Fritz, G.;Leclerc, E.;Kooi, C.W.;Heizmann, C.W.;Chazin, W.J. "The extracellular region of the receptor for advanced glycation end products is composed of two independent structural units." Biochemistry 46, 23 (2007): 6957-70. [PubMed Link] | [ Full text ]
  • Vander Kooi, C.W.;Jusino, M.A.;Perman, B.;Neau, D.B.;Bellamy, H.D.;Leahy, D.J. "Structural basis for ligand and heparin binding to neuropilin B domains." Proceedings of the National Academy of Sciences of the United States of America 104, 15 (2007): 6152-7. [PubMed Link] | [ Full text ]
  • Vander Kooi, C.W.;Ohi, M.D.;Rosenberg, J.A.;Oldham, M.L.;Newcomer, M.E.;Gould, K.L.;Chazin, W.J. "The Prp19 U-box crystal structure suggests a common dimeric architecture for a class of oligomeric E3 ubiquitin ligases." Biochemistry 45, 1 (2006): 121-30. [PubMed Link] | [ Full text ]
  • Malmendal, A.;Vander Kooi, C.W.;Nielsen, N.C.;Chazin, W.J. "Calcium-modulated S100 protein-phospholipid interactions. An NMR study of calbindin D9k and DPC." Biochemistry 44, 17 (2005): 6502-12. [PubMed Link] | [ Full text ]
  • Ohi, M.D.;Vander Kooi, C.W.;Rosenberg, J.A.;Ren, L.;Hirsch, J.P.;Chazin, W.J.;Walz, T.;Gould, K.L. "Structural and functional analysis of essential pre-mRNA splicing factor Prp19p." Molecular and cellular biology 25, 1 (2005): 451-60. [PubMed Link] | [ Full text ]
  • 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. "The glucose-6-phosphatase catalytic subunit gene promoter contains both positive and negative glucocorticoid response elements." Molecular endocrinology (Baltimore, Md.) 19, 12 (2005): 3001-22. [PubMed Link] | [ Full text ]
  • Ohi, M.D.;Vander Kooi, C.W.;Rosenberg, J.A.;Chazin, W.J.;Gould, K.L. "Structural insights into the U-box, a domain associated with multi-ubiquitination." Nature structural biology 10, 4 (2003): 250-5. [PubMed Link] | [ Full text ]
  • Hall, D.A.;Vander Kooi, C.W.;Stasik, C.N.;Stevens, S.Y.;Zuiderweg, E.R.;Matthews, R.G. "Mapping the interactions between flavodoxin and its physiological partners flavodoxin reductase and cobalamin-dependent methionine synthase." Proceedings of the National Academy of Sciences of the United States of America 98, 17 (2001): 9521-6. [PubMed Link] | [ Full text ]
  • Pellecchia, M.;Montgomery, D.L.;Stevens, S.Y.;Vander Kooi, C.W.;Feng, H.P.;Gierasch, L.M.;Zuiderweg, E.R. "Structural insights into substrate binding by the molecular chaperone DnaK." Nature structural biology 7, 4 (2000): 298-303. [PubMed Link] | [ Full text ]
  • Pellecchia, M.;Vander Kooi, C.W.;Keliikuli, K.;Zuiderweg, E.R. "Magnetization transfer via residual dipolar couplings: application to proton-proton correlations in partially aligned proteins." Journal of magnetic resonance (San Diego, Calif. : 1997) 143, 2 (2000): 435-9. [PubMed Link] | [ Full text ]
  • Vander Kooi, C.W.;Kupce, E.;Zuiderweg, E.R.;Pellecchia, M. "Line narrowing in spectra of proteins dissolved in a dilute liquid crystalline phase by band-selective adiabatic decoupling: application to 1HN-15N residual dipolar coupling measurements." Journal of biomolecular NMR 15, 4 (1999): 335-8. [PubMed Link] |