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

  1. Kim M, Nitschké M, Sennino B, Murer P, Schriver BJ, Bell A, Subramanian A, McDonald CE, Wang J, Cha H, Bourgeois-Daigneault MC, Kirn DH, Bell JC, De Silva N, Breitbach CJ, McDonald DM. Amplification of Oncolytic Vaccinia Virus Widespread Tumor Cell Killing by Sunitinib through Multiple Mechanisms. Cancer Res. 2018 Feb 15; 78(4):922-937.
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  2. Shepherd J, Fisher M, Welford A, McDonald DM, Kanthou C, Tozer GM. The protective role of sphingosine-1-phosphate against the action of the vascular disrupting agent combretastatin A-4 3-O-phosphate. Oncotarget. 2017 Nov 10; 8(56):95648-95661.
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  3. Baluk P, Yao LC, Flores JC, Choi D, Hong YK, McDonald DM. Rapamycin reversal of VEGF-C-driven lymphatic anomalies in the respiratory tract. JCI Insight. 2017 Aug 17; 2(16).
    View on PubMed
  4. Nitschké M, Bell A, Karaman S, Amouzgar M, Rutkowski JM, Scherer PE, Alitalo K, McDonald DM. Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations. Am J Pathol. 2017 Sep; 187(9):1984-1997.
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  5. Kim M, Allen B, Korhonen EA, Nitschké M, Yang HW, Baluk P, Saharinen P, Alitalo K, Daly C, Thurston G, McDonald DM. Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation. J Clin Invest. 2016 Sep 01; 126(9):3511-25.
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  6. Korhonen EA, Lampinen A, Giri H, Anisimov A, Kim M, Allen B, Fang S, D'Amico G, Sipilä TJ, Lohela M, Strandin T, Vaheri A, Ylä-Herttuala S, Koh GY, McDonald DM, Alitalo K, Saharinen P. Tie1 controls angiopoietin function in vascular remodeling and inflammation. J Clin Invest. 2016 Sep 01; 126(9):3495-510.
    View on PubMed
  7. Moen I, Gebre M, Alonso-Camino V, Chen D, Epstein D, McDonald DM. Anti-metastatic action of FAK inhibitor OXA-11 in combination with VEGFR-2 signaling blockade in pancreatic neuroendocrine tumors. Clin Exp Metastasis. 2015 Dec; 32(8):799-817.
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  8. Le CT, Laidlaw G, Morehouse CA, Naiman B, Brohawn P, Mustelin T, Connor JR, McDonald DM. Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-a in suppressing remodeling of blood vessels and lymphatics in airway inflammation. Am J Pathol. 2015 Nov; 185(11):2949-68.
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  9. Huang JL, Woolf AS, Kolatsi-Joannou M, Baluk P, Sandford RN, Peters DJ, McDonald DM, Price KL, Winyard PJ, Long DA. Vascular Endothelial Growth Factor C for Polycystic Kidney Diseases. J Am Soc Nephrol. 2016 Jan; 27(1):69-77.
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  10. Raymond WW, Xu X, Nimishakavi S, Le C, McDonald DM, Caughey GH. Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux. PLoS One. 2015; 10(5):e0125797.
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  11. Bose O, Baluk P, Looney MR, Cheng LE, McDonald DM, Caughey GH, Krummel MF. Mast cells present protrusions into blood vessels upon tracheal allergen challenge in mice. PLoS One. 2015; 10(3):e0118513.
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  12. Baluk P, Phillips K, Yao LC, Adams A, Nitschké M, McDonald DM. Neutrophil dependence of vascular remodeling after Mycoplasma infection of mouse airways. Am J Pathol. 2014 Jun; 184(6):1877-89.
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  13. Baluk P, Adams A, Phillips K, Feng J, Hong YK, Brown MB, McDonald DM. Preferential lymphatic growth in bronchus-associated lymphoid tissue in sustained lung inflammation. Am J Pathol. 2014 May; 184(5):1577-92.
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  14. Yao LC, Testini C, Tvorogov D, Anisimov A, Vargas SO, Baluk P, Pytowski B, Claesson-Welsh L, Alitalo K, McDonald DM. Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period. Circ Res. 2014 Feb 28; 114(5):806-22.
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  15. Yao LC, McDonald DM. Plasticity of airway lymphatics in development and disease. Adv Anat Embryol Cell Biol. 2014; 214:41-54.
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  16. Xu X, Greenland J, Baluk P, Adams A, Bose O, McDonald DM, Caughey GH. Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis. Am J Respir Cell Mol Biol. 2013 Sep; 49(3):437-44.
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  17. Khurana A, Chapelin F, Beck G, Lenkov OD, Donig J, Nejadnik H, Messing S, Derugin N, Chan RC, Gaur A, Sennino B, McDonald DM, Kempen PJ, Tikhomirov GA, Rao J, Daldrup-Link HE. Iron administration before stem cell harvest enables MR imaging tracking after transplantation. Radiology. 2013 Oct; 269(1):186-97.
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  18. Miller CN, Hartigan-O'Connor DJ, Lee MS, Laidlaw G, Cornelissen IP, Matloubian M, Coughlin SR, McDonald DM, McCune JM. IL-7 production in murine lymphatic endothelial cells and induction in the setting of peripheral lymphopenia. Int Immunol. 2013 Aug; 25(8):471-83.
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  19. Sennino B, Ishiguro-Oonuma T, Schriver BJ, Christensen JG, McDonald DM. Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice. Cancer Res. 2013 Jun 15; 73(12):3692-703.
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  20. Morrisey EE, Cardoso WV, Lane RH, Rabinovitch M, Abman SH, Ai X, Albertine KH, Bland RD, Chapman HA, Checkley W, Epstein JA, Kintner CR, Kumar M, Minoo P, Mariani TJ, McDonald DM, Mukouyama YS, Prince LS, Reese J, Rossant J, Shi W, Sun X, Werb Z, Whitsett JA, Gail D, Blaisdell CJ, Lin QS. Molecular determinants of lung development. Ann Am Thorac Soc. 2013 Apr; 10(2):S12-6.
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