George E. Davis, MD, PhD
Research Interests
Davis' laboratory focuses on the following questions relevant to angiogenesis, wound repair and cancer research:
- How do endothelial cells form cell-lined tube structures with lumens in three-dimensional (3D) extracellular matrices?
- How do endothelial cells and other cell types such as tumor cells invade 3D matrices?
- To what extent do endothelial cells directly or indirectly play a role in tumor invasion and metastasis?
- What molecular events control the process of vascular regression?
- How do vascular supporting cells such as pericytes stabilize vascular tubes?
- How do distinct matrix metalloproteinases and their inhibitors control the processes of vascular morphogenesis versus regression in 3D matrices?
- How do extracellular matrix fragments (matricryptins) regulate vascular morphogenesis versus regression in normal versus diseased states (e.g. diabetes)?
Research Description
Methodology/Techniques
We have developed microassay approaches to study human endothelial cell tube morphogenesis and regression in 3D matrices. We perform time-lapse imaging of tube formation and regression, endothelial cell invasion and tumor cell invasion of 3D matrices. We use cellular and molecular biological approaches such siRNA knockdown, recombinant adenoviral and lentiviral vectors to deliver wild-type and mutant genes to cells to assess function in these biological contexts.
Professional Background
- BS in microbiology, Arizona State University
- MD, PhD, University of California, San Diego, PhD in Biology- Role of extracellular matrix in neurite outgrowth
- Anatomic Pathology Residency- National Institutes of Health
- Postdoctoral Research- Burnham Institute, La Jolla, CA
- Assistant to Full Professor, Department of Pathology, Texas A&M College of Medicine
- Past chairperson and member, NIH Cardiovascular Differentiation and Development study section
- Past member, NIH Pathology A study section
- Research funded by the National Institutes of Health
Selected Publications
Bowers, S.L.K., Meng, C., Davis, M.T., and Davis, G.E. (2014) Investigating human vascular tube morphogenesis and maturation using endothelial cell-pericyte co-cultures and a doxycycline-inducible genetic system in 3D extracellular matrices, Methods Mol. Biol., in press.
Smith, A.O., Bowers, S.L.K., Stratman, A.N., and Davis, G.E. (2013) Hematopoietic stem cell cytokines and fibroblast growth factor-2 stimulate human endothelial cell-pericyte tube co-assembly in 3D fibrin matrices under serum-free defined conditions, PLoS One, 8:e85147.
Morin, K.T., Smith, A.O., Davis, G.E., and Tranquillo, R.T. (2013) Aligned human microvessels formed in 3D fibrin gel by constraint of gel contraction, Microvasc. Res., 90:12-22.
Davis, G.E., Kim, D.J., Meng, C., Norden, P.R., Speichinger, K.R., Davis, M.T., Smith, A.O., Bowers, S.L.K., and Stratman, A.N. (2013) Control of vascular tube morphogenesis and maturation in 3D extracellular matrices by endothelial cells and pericytes, Methods Mol. Biol., 1066:17-28.
Kim, D.J., Martinez-Lemus, L.A., and Davis, G.E. (2013) EB1, p150Glued and Clasp1 control endothelial tubulogenesis through microtubule assembly, acetylation and apical polarization, Blood, 121:3521-3530.
Lanahan A.A., Zhang X., Fantin A., Zhuang Z.W., Felix Y.Y.Y., Speichinger, K.R., Prahst, C., Zhang, J., Davis, G.E., Toomre, D., Ruhrberg, C., and Simons, M. (2013) The Neuropilin-1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis, Dev. Cell, 25:156-168.
Zheng, X., Xu, C., Smith, A.O., Stratman, A.N., Zou, Z., Kleaveland, B., Yuan, L., Didiku, C., Sen, A., Liu, X., Skuli, N., Zaslavsky, A., Chen, M., Cheng, L., Davis, G.E., and Kahn, M.L. (2012) Dynamic regulation of the cerebral cavernous malformation pathway controls vascular stability and growth, Dev. Cell, 23:342-355.
Stratman, A.N., Kim, D. J., Sacharidou, A., Speichinger, K.R., and Davis, G.E. (2012) Methodologic approaches to investigate vascular tube morphogenesis and maturation events in 3D extracellular matrices in vitro and in vivo. In The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications, Eds. E. Zudaire and F. Cuttitta, Springer, pgs. 101-125.
Schrimpf, C., Xin, C., Campanholle, G., Gill, S.E., Stallcup, W., Lin, S-L., Parekh, D.J., Venkatachalam, M., Davis, G.E., Gharib, S.A., Humphreys, B.D., and Duffield, J.S. (2012) Pericyte-derived TIMP-3 and ADAMTS1 regulate vascular stability after kidney injury, J. Amer. Soc. Nephrol., 23:868-883.
Yuan, L., Le Bras, A., Sacharidou, A., Itagaki, K., Zhan, Y., Kondo, M., Carman, C., Davis, G.E., Aird, W.C., and Oettgen, P. (2012) ETS-related gene (Erg) controls endothelial cell permeability via transcriptional regulation of the claudin-5 (CLDN5) gene, J. Biol. Chem., 287:6582-6591.
Davis, G.E. (2012) Molecular regulation of vasculogenesis and angiogenesis: Recent advances and future directions. In Molecular and Translational Vascular Medicine, Eds. J.W. Homeister and M.S. Willis, Springer, pgs. 169-206.
Pan, W., Pham, V.N., Stratman, A.N., Castranova, D., Kamei, M., Kidd, K.R., Lo, B.D., Shaw, K.M., Torres-Vasquez, J., Mikelis, C.M., Gutkind, J.S., Davis, G.E., and Weinstein, B.M. (2012) CDP-diacylglycerol synthetase-controlled phosphatidylinositol 4,5-bisphosphate availability limits VEGFa signaling and vascular morphogenesis, Blood, 120:489-498.
Stratman, A.N., and Davis, G.E. (2012) Endothelial cell-pericyte interactions stimulate basement membrane matrix assembly: Influence on vascular tube remodeling, maturation and stabilization, Microscopy and Microanalysis, 18:68-80.
Sacharidou, A., Stratman, A.N., and Davis, G.E. (2012) Molecular mechanisms controlling vascular lumen formation in three-dimensional extracellular matrices, Cells Tissues Organs (special issue), 195:122-143.
Mackman, N. and Davis, G.E. (2011) Blood coagulation and blood vessel development: is tissue factor the missing link?, Arterioscler. Thromb. Vasc. Biol. 31:2364-2366.
Davis, G.E. (2011) Angiogenesis and Proteinases: Influence on Vascular Morphogenesis,Stabilization and Regression, Drug Discovery Today: Disease Models, 8:13-20.
Stratman, A.N., Davis, M.J., and Davis, G.E. (2011) VEGF and FGF prime vascular tube morphogenesis and sprouting in response to hematopoietic stem cell cytokines, Blood, 117: 3709-3719.
Yuan L, Sacharidou A, Stratman AN, Le Bras A, Zwiers PJ, Spokes K, Bhasin M, Shih SC, Nagy JA, Molema G, Aird WC, Davis GE, Oettgen P., RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG., Blood. 2011 Jul 28;118(4):1145-53. Epub 2011 May 31. PMID: 21628409
Chan AC, Drakos SG, Ruiz OE, Smith AC, Gibson CC, Ling J, Passi SF, Stratman AN, Sacharidou A, Revelo MP, Grossmann AH, Diakos NA, Davis GE, Metzstein MM, Whitehead KJ, Li DY., Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice.,J Clin Invest. 2011 May 2;121(5):1871-81. doi: 10.1172/JCI44393. Epub 2011 Apr 1.PMID: 21490399
Davis GE, Stratman AN, Sacharidou A, Koh W., Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting., Int Rev Cell Mol Biol. 2011;288:101-65. doi: 10.1016/B978-0-12-386041-5.00003-0. Review.PMID: 21482411
Xu K, Sacharidou A, Fu S, Chong DC, Skaug B, Chen ZJ, Davis GE, Cleaver O, Blood vessel tubulogenesis requires Rasip1 regulation of GTPase signaling., Dev Cell. 2011 Apr 19;20(4):526-39. Epub 2011 Mar 10., PMID: 21396893
Stratman AN, Davis MJ, Davis GE., VEGF and FGF prime vascular tube morphogenesis and sprouting directed by hematopoietic stem cell cytokines., Blood. 2011 Apr 7;117(14):3709-19. Epub 2011 Jan 14.PMID: 21239704
Davis GE., Vascular balancing act: EGFL7 and Notch., Blood. 2010 Dec 23;116(26):5791-3. No abstract available.PMID:21183697
Chao JT, Gui P, Zamponi GW, Davis GE, Davis MJ., Spatial association of the Cav1.2 calcium channel with α5β1-integrin.,Am J Physiol Cell Physiol. 2011 Mar;300(3):C477-89. Epub 2010 Dec 22.PMID: 21178109
Stratman AN, Schwindt AE, Malotte KM, Davis GE., Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization., Blood. 2010 Nov 25;116(22):4720-30. Epub 2010 Aug 25.PMID: 20739660
Gui P, Chao JT, Wu X, Yang Y, Davis GE, Davis MJ., Coordinated regulation of vascular Ca2+ and K+ channels by integrin signaling., Adv Exp Med Biol. 2010;674:69-79. Review.PMID: 20549941
Davis GE., The development of the vasculature and its extracellular matrix: a gradual process defined by sequential cellular and matrix remodeling events., Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H245-7. Epub 2010 Jun 11. No abstract available. PMID: 20543090
Sacharidou A, Koh W, Stratman AN, Mayo AM, Fisher KE, Davis GE., Endothelial lumen signaling complexes control 3D matrix-specific tubulogenesis through interdependent Cdc42- and MT1-MMP-mediated events., Blood. 2010 Jun 24;115(25):5259-69. Epub 2010 Mar 9.PMID:20215637
Fisher KE, Sacharidou A, Stratman AN, Mayo AM, Fisher SB, Mahan RD, Davis MJ, Davis GE., MT1-MMP- and Cdc42-dependent signaling co-regulate cell invasion and tunnel formation in 3D collagen matrices.,J Cell Sci. 2009 Dec 15;122(Pt 24):4558-69. Epub 2009 Nov 24.PMID: 19934222
Yang Y, Wu X, Gui P, Wu J, Sheng JZ, Ling S, Braun AP, Davis GE, Davis MJ., Alpha5beta1 integrin engagement increases large conductance, Ca2+-activated K+ channel current and Ca2+ sensitivity through c-src-mediated channel phosphorylation., J Biol Chem. 2010 Jan 1;285(1):131-41. Epub 2009 Nov 3.PMID: 19887442
Kamei, M., Saunders. W.B., Bayless, K.J., Dye, L., Davis. G.E., and Weinstein, B.M. (2006) Endothelial tubes assemble from intracellular vacuoles in vivo. Nature, 442: 453-456.
Saunders, W.B., Bohnsack, B.L., Faske, J.B., Anthis, N.J., Bayless, K.J., Hirschi, K.K. and Davis, G.E. (2006) Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J. Cell Biol., in press.
Davis, G.E. and Saunders, W.B. (2006) Molecular balance of capillary tube formation versus regression in wound repair: Role of matrix metalloproteinases and their inhibitors. J. Invest. Dermatol., in press.
Davis, G.E., and Senger, D.R. (2005) Endothelial-ECM: Biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ. Res., 97:1093-1107.
Saunders, W.B., Bayless, K.J. and Davis, G.E. (2005) MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. J. Cell Sci., 118: 2325-2340.
Bayless, K.J., and Davis, G.E. (2004) Microtubule depolymerization rapidly collapses capillary tube networks in vitro and angiogenic vessels in vivo through the small GTPase Rho. J. Biol. Chem., 279: 11686-11695.
Bayless, K.J. and Davis, G.E. (2002) The Cdc42 and Rac1 GTPases are required for capillary lumen formation in three-dimensional extracellular matrices, J. Cell Sci., 115:1123-1136.
Davis, G.E., Bayless, K.J., and Mavila, A. (2002) The molecular basis of endothelial cell morphogenesis in three-dimensional extracellular matrices, Anat. Rec., 268:252-275.
Davis, G.E., Bayless, K.J., Davis, M.J., and Meininger, G.A. (2000) Regulation of tissue injury responses by the exposure of matricryptic sites within extracellular matrix molecules, Am. J. Pathol., 156:1489-1498.
