Donald M. McDonald

Donald M. McDonald, MD, PhD, Professor
donald.mcdonald@ucsf.edu
Administrative Assistant: 415-476-2118
McDonald Lab Website

Angiogenesis and Microvascular Remodeling in Chronic Inflammation and Cancer

Image

The McDonald laboratory is studying the cellular mechanisms of angiogenesis, vascular remodeling, and plasma leakage in animal models of chronic inflammation and cancer. The goal is to identify abnormalities of the vasculature that can be used as the basis of novel treatments. In one area of research, we are identifying novel targets on blood vessels in normal organs and tumors by using probes that bind to specific molecular addresses identified using random peptide phage libraries. Another research area concerns the cellular mechanisms of plasma leakage in disease. Here, the leakage from tumor vessels, due to a defective endothelial monolayer, contrasts with leakage in inflammation, where intercellular gaps form in seconds and reseal spontaneously. We are also studying the mechanism of the effects of angiopoietins on vessel leakiness following our discovery that angiopoietin-1 reduces leakage. A third area of interest is the mechanism and reversibility of vascular remodeling, angiogenesis, and lymphangiogenesis in chronic inflammation and tumors. We are using Mycoplasma pulmonis infection of the airways of normal, transgenic, and knockout mice to identify the cells and growth factors that mediate vascular remodeling in chronic inflammation and are using the abnormal vasculature as a therapeutic target. Finally, we are examining the mechanism of action and cellular effects of angiogenesis inhibitors in cancer.

Complete list of Publications/PubMed

Selected Publications

2000-2006

Nakahara T, Norberg SM, Shalinsky DR, Hu-Lowe DD, McDonald DM. Effect of inhibition of vascular endothelial growth factor signaling on distribution of extravasated antibodies in tumors. Cancer Res. 2006 Feb 1;66(3):1434-45.

McDonald DM, Baluk P.Imaging of angiogenesis in inflamed airways and tumors: newly formed blood vessels are not alike and may be wildly abnormal: Parker B. Francis lecture. Chest. 2005 Dec;128(6 Suppl):602S-608S.

Aurora AB, Baluk P, Zhang D, Sidhu SS, Dolganov GM, Basbaum C, McDonald DM, Killeen N.Immune complex-dependent remodeling of the airway vasculature in response to a chronic bacterial infection. J Immunol. 2005 Nov 15;175(10):6319-26.

Xu X, Zhang D, Lyubynska N, Wolters PJ, Killeen NP, Baluk P, McDonald DM, Hawgood S, Caughey GH. Mast cells protect mice from Mycoplasma pneumonia. Am J Respir Crit Care Med. 2006 Jan 15;173(2):219-25. Epub 2005 Oct 6.

Ozawa MG, Yao VJ, Chanthery YH, Troncoso P, Uemura A, Varner AS, Kasman IM, Pasqualini R, Arap W, McDonald DM. Angiogenesis with pericyte abnormalities in a transgenic model of prostate carcinoma. Cancer. 2005 Nov 15;104(10):2104-15.

Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, Norberg SM, O'Brien SM, Davis RB, Gowen LC, Anderson KD, Thurston G, Joho S, Springer ML, Kuo CJ, McDonald DM. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H560-76. Epub 2005 Sep 19.

Baffert F, Le T, Sennino B, Thurston G, Kuo CJ, Hu-Lowe D, McDonald DM. Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H547-59. Epub 2005 Sep 19.

Baffert F, Le T, Thurston G, McDonald DM. Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules. Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H107-18. Epub 2005 Aug 26.

di Tomaso E, Capen D, Haskell A, Hart J, Logie JJ, Jain RK, McDonald DM, Jones R, Munn LL. Mosaic tumor vessels: cellular basis and ultrastructure of focal regions lacking endothelial cell markers. Cancer Res. 2005 Jul 1;65(13):5740-9.

Parsons-Wingerter P, Kasman IM, Norberg S, Magnussen A, Zanivan S, Rissone A, Baluk P, Favre CJ, Jeffry U, Murray R, McDonald DM. Uniform Overexpression and Rapid Accessibility of {alpha}5{beta}1 Integrin on Blood Vessels in Tumors. Am J Pathol. 2005 Jul;167(1):193-211.

Cho CH, Kim KE, Byun J, Jang HS, Kim DK, Baluk P, Baffert F, Lee GM, Mochizuki N, Kim J, Jeon BH, McDonald DM, Koh GY. Long-Term and Sustained COMP-Ang1 Induces Long-Lasting Vascular Enlargement and Enhanced Blood Flow. Circ Res. 2005 Jun 16; [Epub ahead of print]

Thurston G, Wang Q, Baffert F, Rudge J, Papadopoulos N, Jean-Guillaume D, Wiegand S, Yancopoulos GD, McDonald DM. Angiopoietin 1 causes vessel enlargement, without angiogenic sprouting, during a critical developmental period. Development. 2005 Jun 15; [Epub ahead of print]

Magnussen A, Kasman IM, Norberg S, Baluk P, Murray R, McDonald DM. Rapid access of antibodies to alpha5beta1 integrin overexpressed on the luminal surface of tumor blood vessels. Cancer Res. 2005 Apr 1;65(7):2712-21.

Yao VJ, Ozawa MG, Trepel M, Arap W, McDonald DM, Pasqualini R. Targeting pancreatic islets with phage display assisted by laser pressure catapult microdissection. Am J Pathol. 2005 Feb;166(2):625-36.

Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, Jeltsch M, Petrova TV, Pytowski B, Stacker SA, Yla-Herttuala S, Jackson DG, Alitalo K, McDonald DM. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest. 2005 Feb 1;115(2):247-257.

Baluk P, Hashizume H, McDonald DM. Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev. 2005 Feb;15(1):102-11.

Baluk P, Lee CG, Link H, Ator E, Haskell A, Elias JA, McDonald DM. Regulated angiogenesis and vascular regression in mice overexpressing vascular endothelial growth factor in airways. Am J Pathol. 2004 Oct;165(4):1071-85.

Lee CG, Link H, Baluk P, Homer RJ, Chapoval S, Bhandari V, Kang MJ, Cohn L, Kim YK, McDonald DM, Elias JA. Vascular endothelial growth factor (VEGF) induces remodeling and enhances T(H)2-mediated sensitization and inflammation in the lung. Nat Med. 2004 Oct;10(10):1095-103. Epub 2004 Sep 19.

Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004 Jul;165(1):35-52.

Baluk P, Raymond WW, Ator E, Coussens LM, McDonald DM, Caughey GH. Matrix metalloproteinase 2 and 9 expression increases in mycoplasma-infected airways but is not required for microvascular remodeling. Am J Physiol Lung Cell Mol Physiol. 2004 Apr 9 [Epub ahead of print]

Baffert F, Thurston G, Rochon-Duck M, Le T, Brekken R, McDonald DM. Age-related changes in vascular endothelial growth factor dependency and angiopoietin-1-induced plasticity of adult blood vessels. Circ Res. 2004 Apr 16;94(7):984-92. Epub 2004 Mar 04.

Ozawa CR, Banfi A, Glazer NL, Thurston G, Springer ML, Kraft PE, McDonald DM, Blau HM. Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J Clin Invest. 2004 Feb;113(4):516-27.

McDonald DM, Teicher BA, Stetler-Stevenson W, Ng SS, Figg WD, Folkman J, Hanahan D, Auerbach R, O'Reilly M, Herbst R, Cheresh D, Gordon M, Eggermont A, Libutti SK. Report from the Society for Biological Therapy and Vascular Biology Faculty of the NCI Workshop on Angiogenesis Monitoring. J Immunother. 2004 Mar-Apr;27(2):161-175.

Denis-Mize KS, Dupuis M, Singh M, Woo C, Ugozzoli M, O'Hagan DT, Donnelly JJ 3rd, Ott G, McDonald DM. Mechanisms of increased immunogenicity for DNA-based vaccines adsorbed onto cationic microparticles. Cell Immunol. 2003 Sep;225(1):12-20.

Baluk P, Morikawa S, Haskell A, Mancuso M, McDonald DM. Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors. Am J Pathol. 2003 Nov;163(5):1801-15.

Favre CJ, Mancuso M, Maas K, McLean JW, Baluk P, McDonald DM. Expression of genes involved in vascular development and angiogenesis in endothelial cells freshly isolated from adult lungs. Am J Physiol Heart Circ Physiol. 2003 Jul 3

McDonald DM, Choyke PL. Imaging of angiogenesis: from microscope to clinic. Nat Med. 2003 Jun;9(6):713-25.

Umemoto EY, Brokaw JJ, Dupuis M, McDonald DM. Rapid changes in shape and number of MHC class II expressing cells in rat airways after Mycoplasma pulmonis infection. Cell Immunol. 2002 Dec;220(2):107-15.

Pasqualini R, Arap W, McDonald DM. Probing the structural and molecular diversity of tumor vasculature. Trends Mol Med 2002 Dec;8(12):563-71.

McDonald DM, Baluk P. Significance of blood vessel leakiness in cancer. Cancer Research 2002 Sep 15;62(18):5381-5.

Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol. 2002 Mar;160(3):985-1000.

McDonald DM. Angiogenesis and remodeling of airway vasculature in chronic inflammation. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 2):S39-45.

Dupuis M, Denis-Mize K, LaBarbara A, Peters W, Charo IF, McDonald DM, Ott G. Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis. Eur J Immunol. 2001 Oct;31(10):2910-8.

Elson DA, Thurston G, Huang LE, Ginzinger DG, McDonald DM, Johnson RS, Arbeit JM. Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1alpha. Genes Dev. 2001 Oct 1;15(19):2520-32.

Pasqualini R, McDonald DM, Arap W. Vascular targeting and antigen presentation. Nat Immunol. 2001 Jul;2(7):567-8.

Ezaki T, Baluk P, Thurston G, La Barbara A, Woo C, McDonald DM. Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation. Am J Pathol. 2001 Jun;158(6):2043-55.

Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova TV, Kubo H, Thurston G, McDonald DM, Achen MG, Stacker SA, Alitalo K. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 2001 Mar 15;20(6):1223-31.

Denis-Mize KS, Dupuis M, MacKichan ML, Singh M, Doe B, O'Hagan D, Ulmer JB, Donnelly JJ, McDonald DM, Ott G. Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells. Gene Ther. 2000 Dec;7(24):2105-12.

McDonald DM, Foss AJ. Endothelial cells of tumor vessels: abnormal but not absent. Cancer Metastasis Rev. 2000;19(1-2):109-20. Review.

Gale NW, Baluk P, Pan L, Kwan M, Holash J, DeChiara TM, McDonald DM, Yancopoulos GD. Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells. Dev Biol. 2001 Feb 15;230(2):151-60.

Kwan ML, Gomez AD, Baluk P, Hashizume H, McDonald DM. Airway vasculature after mycoplasma infection: chronic leakiness and selective hypersensitivity to substance P. Am J Physiol Lung Cell Mol Physiol. 2001 Feb;280(2):L286-97. PMID: 11159008 [PubMed - indexed for MEDLINE]

Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14608-13.

Thurston G, Maas K, Labarbara A, Mclean JW, McDonald DM. Microvascular remodelling in chronic airway inflammation in mice. Clin Exp Pharmacol Physiol. 2000 Oct;27(10):836-41.

Dupuis M, Denis-Mize K, Woo C, Goldbeck C, Selby MJ, Chen M, Otten GR, Ulmer JB, Donnelly JJ, Ott G, McDonald DM. Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice. J Immunol. 2000 Sep 1;165(5):2850-8.

Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, McDonald DM. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol. 2000 Apr;156(4):1363-80.

Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 2000 Apr;6(4):460-3.

Thurston G, Baluk P, McDonald DM. Determinants of endothelial cell phenotype in venules. Microcirculation. 2000 Feb;7(1):67-80. Review.

McDonald DM, Munn L, Jain RK. Vasculogenic mimicry: how convincing, how novel, and how significant? Am J Pathol. 2000 Feb;156(2):383-8. Review.

Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science. 1999 Dec 24;286(5449):2511-4.