University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Donald M. McDonald, MD, PhD

Donald M. McDonald, MD, PhD

Professor, Department of Anatomy, UCSF

Cancer Center Program Memberships

Cancer Immunology

Research Summary

Research in my laboratory is examining the cellular mechanisms of lymphangiogenesis, angiogenesis, and vascular remodeling in mouse models of chronic inflammation and cancer, with a focus on the respiratory tract. We use in vivo cell biological approaches to determine how abnormalities of lymphatics and blood vessels contribute to disease pathophysiology. My current interests include developing approaches for preventing, stopping, or reversing disease-related changes in lymphatics and blood vessels and learning the consequences of these actions. Related interests include the regulation of endothelial barrier function, downstream effects of altered plasma leakage, and control mechanisms of tissue fluid and cell clearance by lymphatics. Projects in the laboratory use mouse models to dissect the role of key growth factors and receptors involved in growth and remodeling of lymphatics and blood vessels and related disease processes. VEGF-C, VEGF-A, angiopoietins, TNF-alpha, HGF, and their receptors are of current interest. In mouse models, signaling is manipulated in vivo by switchable transgenic overexpression, genetic deletion, viral vectors, or pharmacological agonists or inhibitors. Ongoing studies are using the models to examine factors that drive or modify remodeling of lymphatics and blood vessels in inflammatory conditions in the lung and airways. We are also studying favorable and potentially unfavorable effects of growing or destroying lymphatics and/or blood vessels in the lung or in tumors, reflected by tumor growth, invasion, and metastasis. The overall goal is to advance the understanding and development of strategies that can stop or reverse lymphangiogenesis and angiogenesis and to characterize the downstream benefits and consequences of these changes in inflammatory disease and cancer.

Education

University of California, Berkeley, A.B., 1961, Zoology
University of California, San Francisco, M.D., 1965
University of Iowa, Iowa City, 1965-1966, Internal Medicine
NIH Graduate Division, Bethesda, 1966-1969, Cell Biology & Neuroscience
University of California, San Francisco, Ph.D., 1974, Cell Biology & Endocrinology


Professional Experience

  • 1966-67
    Staff Associate, Program Projects Branch, Extramural Programs, NHLBI, NIH, Bethesda, MD
  • 1967-69
    Staff Associate, Section on Functional Neuroanatomy, Laboratory of Neuropathology and Neuroanatomical Science, NINDS, NIH, Bethesda, MD
  • 1969-72
    NIH Special Fellowship, Cardiovascular Research Institute, UCSF
  • 1973-78
    Assistant Professor of Anatomy, UCSF
  • 1973-90
    Associate Staff, Cardiovascular Research Institute, UCSF
  • 1973-98
    Head, Pulmonary Core Microscopy Laboratory, Cardiovascular Research Institute, UCSF
  • 1978-84
    Associate Professor of Anatomy, UCSF
  • 1981-90
    Associate Director, Pulmonary Training Program, Cardiovascular Research Institute, UCSF
  • 1984-
    Professor of Anatomy, UCSF
  • 1990-98
    Senior Staff, Cardiovascular Research Institute, UCSF
  • 1999-
    Investigator, Cardiovascular Research Institute, UCSF
  • 2001-present
    Member, Comprehensive Cancer Center, UCSF

Selected Publications

  • Pasqualini, R., D.M McDonald, and W. Arap. Vascular targeting and antigen presentation. Nat. Immunol. 2: 567-568, 2001.
  • Ezaki, T., P. Baluk, G. Thurston, A. La Barbara, and D.M. McDonald. Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation. Am. J. Pathol. 158: 2043-2055, 2001.
  • Elson, D.A., G. Thurston, L.E. Huang, D.G. Ginzinger, D.M. McDonald, R.S. Johnson, and J.M. Arbeit. Induction of hypervascularity without leak or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1a. Genes Dev., 15: 2520-2532, 2001.
  • Kwan, M.L., A.D. Gomez, P. Baluk, H. Hashizume, and D.M. McDonald. Airway vasculature after mycoplasma infection: chronic leakiness and selective hypersensitivity to substance P. Am. J. Physiol. 280:L286-L297, 2001.
  • Gale, N.W., P. Baluk, L. Pan, M. Kwan, J. Holash, T.M. DeChiara, D.M. McDonald, and G.D. Yancopoulos. Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells. Dev. Biol. 230:151-160, 2001.
  • McDonald, D.M. and A.J.E. Foss. Endothelial cells of tumor vessels: Abnormal but not absent. Cancer and Metastasis Reviews, 19:109-120, 2000.
  • Thurston, G., J.S. Rudge, E. Ioffe, H. Zhou, L. Ross, S.D. Croll, S. Mahon, N. Glazer, J. Holash, D.M. McDonald, and G.D. Yancopoulos. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nature Medicine, 6: 460-463, 2000.
  • Thurston, G., K. Maas, A. LaBarbara, J.W. McLean, and D.M. McDonald. Microvascular Remodeling in chronic airway inflammation in mice. Clin. Exp. Pharm. Physiol., 27:836-841, 2000.
  • Chang YS, E. di Tomaso, D.M. McDonald, R. Jones, R.K. Jain, L.L. Munn. Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood. Proc. Natl. Acad. Sci. U S A 97:14608-14613, 2000.
  • Thurston, G., P. Baluk, and D.M. McDonald. Determinants of endothelial cell phenotype in venules. Microcirculation, 7: 67-80, 2000.
  • McDonald, D.M., L. Munn, and R.K. Jain. Vasculogenic mimicry: How convincing, how novel, and how significant? Am J Pathol 156: 383-388, 2000.
  • Hashizume, H., P. Baluk, S. Morikawa, J.W. McLean, G. Thurston, S. Roberge, R.K. Jain, and D.M. McDonald. Openings between defective endothelial cells explain tumor vessel leakiness. Am. J. Pathol., 156: 1363-1380, 2000.
  • Denis-Mize K.S., M. Dupuis, M.L. MacKichan, M. Singh, B. Doe, D. O'Hagan, J.B. Ulmer, J.J. Donnelly, D.M. McDonald, and G. Ott. Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells. Gene Therapy 7: 21052112, 2000.
  • Dupuis, M., K. Denis-Mize, C. Woo, C. Goldbeck, M.J. Selby, M. Chen, G.R. Otten, J.B. Ulmer, J.J. Donnelly, G. Ott, and D.M. McDonald. Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice. J. Immunol., 165:2850-2858, 2000.
  • Thurston, G., C. Suri, K. Smith, J. McClain, T.N. Sato, G.D. Yancopoulos, and D.M. McDonald. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science, 286: 2511-2514, 1999.
  • Murphy, T.J., G. Thurston, T. Ezaki, and D.M. McDonald. Endothelial cell heterogeneity in venules of mouse airways induced by polarized inflammatory stimulus. Am. J. Pathol. 155: 93-103, 1999.
  • McDonald, D.M., G. Thurston, and P. Baluk. Endothelial gaps as sites for plasma leakage in inflammation. Microcirculation 6: 7-22, 1999.
  • Corada, M., M. Mariotti, G. Thurston, K. Smith, R. Kunkel, M. Brockhaus, M.G. Lampugnani, I. Martin-Padura, A. Stoppacciaro, L. Ruco, D.M. McDonald, P. Ward, and E. Dejana. Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc. Natl. Acad. Sci. USA 96: 9815-9820, 1999.
  • Dahlqvist, A., E.M. Umemoto, J.J. Brokaw, M. Dupuis, and D.M. McDonald. Tissue macrophages associated with angiogenesis in chronic airway inflammation in rats. Am. J. Respir. Cell Mol. Biol. 20: 237-247, 1999.
  • Baluk, P., G. Thurston, T.J. Murphy, N.W. Bunnett, and D.M. McDonald. Neurogenic plasma leakage in mouse airways. Br. J. Pharm. 126: 522-528, 1999.
  • Dupuis, M., T.J. Murphy, D. Higgins, M. Ugozzoli, G. van Nest, G. Ott, and D.M. McDonald. Dendritic cells internalize vaccine adjuvant after intramuscular injection. Cell. Immunol., 186: 18-27, 1998.
  • Suri, C., J. McClain, G. Thurston, D.M. McDonald, H. Zhou, E.H. Oldmixon, T.N. Sato, and G.D. Yancopoulos. Increased vascularization in mice overexpressing Angiopoietin-1. Science 282: 468-471, 1998.
  • Thurston, G., J.W. McLean, M. Rizen, P. Baluk, A. Haskell, T. J. Murphy, D. Hanahan, and D.M. McDonald. Cationic liposomes target angiogenic endothelial cells in tumors and inflammation in mice. J. Clin. Invest. 101: 1401-1413, 1998.
  • Thurston, G., T.J. Murphy, P. Baluk, J.R. Lindsey, and D.M. McDonald. Angiogenesis in mice with chronic airway inflammation: Strain-dependent differences. Am. J. Pathol. 153: 1099-1112, 1998.
  • Brokaw, J.J., G.W. White, P. Baluk, G.P. Anderson, E.Y. Umemoto, and D.M. McDonald. Glucocorticoid-induced apoptosis of dendritic cells in the rat tracheal mucosa. Am. J. Respir. Cell Mol Biol. 19: 598-605, 1998.
  • Baluk, P, N.W. Fine, H.A. Thomas, E.T. Wei, and D.M. McDonald. Anti-inflammatory mystixin peptides inhibit plasma leakage without blocking endothelial gap formation. J. Pharm. Exp. Therap. 284: 693-699, 1998.
  • Baluk, P., P. Bolton, A. Hirata, G. Thurston, and D.M. McDonald. Endothelial gaps and adherent leukocytes in allergen-induced early- and late-phase plasma leakage in rat airways. Am. J. Pathol. 152:1463-1476, 1998.
  • selected prior publications
  • McLean, J.W., E.A. Fox, P. Baluk, P.B. Bolton, A. Haskell, R. Pearlman, G. Thurston, E.Y. Umemoto, and D.M. McDonald. Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in mice. Am. J. Physiol. 273: H387-404, 1997.
  • Baluk, P., A. Hirata, G. Thurston, T. Fujiwara, C.R. Neal, C.C. Michel, and D.M. McDonald. Endothelial gaps: Time course of formation and closure in inflamed venules of rats. Am. J. Physiol. 272: L155-170, 1997.
  • Thurston, G., Baluk, P., A. Hirata, and D.M. McDonald. Permeability-related changes revealed at endothelial cell borders in inflamed venules by lectin binding, Am. J. Physiol. 271: H2547-2562, 1996.
  • Bowden, J. J., P. Baluk, P. M. Lefevre, S. R. Vigna, and D.M. McDonald. Substance P (NK1) receptor immunoreactivity on endothelial cells of the rat tracheal mucosa. Am. J. Physiol. 270: L404-414, 1996.
  • Hirata, A., P. Baluk, T. Fujiwara, and D.M. McDonald. Location of focal silver staining at endothelial gaps in inflamed venules examined by scanning electron microscopy. Am. J. Physiol. 269: L403-18, 1995.