Photo of Dai Fukumura,  MD, PhD

Dai Fukumura, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-8143
Fax: (617) 724-5841

Dai Fukumura, MD, PhD

Massachusetts General Hospital


  • Associate Professor, Radiation Oncology, Harvard Medical School
  • Deputy Director, Edwin L. Steele Laboratory, Radiation Oncology, Massachusetts General Hospital


Research Abstract

The long-term goal of my research is to reveal the fundamentals of vascular biology in both physiological and pathophysiological settings, and to exploit this newfound knowledge for the detection and treatment of diseases. Innovative animal models and state of the art imaging techniques are essential to achieve this goal. I have been developing and utilizing such imaging techniques - including an in vivo fluorescent protein gene reporter system (Cell 94: 715, 1998), intravital multiphoton laser-scanning microscopy (Nat Med 7:864, 2001) and optical frequency domain imaging (Nat Med 15: 1219, 2009) in collaboration with world-renowned experts at MGH. With these cutting-edge in vivo imaging approaches we have been providing novel insights into the role of host-tumor interaction in angiogenesis, vascular function, tumor growth, and response to treatment (Nature 416: 279, 2002; PNAS 109: E3119, 2012).

Role of NO in tumor angiogenesis, vascular function and anti-tumor therapy: One of my research interests lie in the role of nitric oxide (NO) in the vasculature and tumors. NO is a highly reactive signaling molecule that mediates a variety of physiological and pathological functions. I discovered that NO derived from vascular endothelial cells not only mediates angiogenesis (PNAS 98: 2604, 2001), but also subsequent maturation of blood vessels (JCI 115: 1816, 2005). I postulated and proved that perivascular gradients of NO – spatial and temporal distribution of NO from vasculature – is crucial in these processes and the disruption of perivascular NO gradients by non-vascular sources of NO results in immature and dysfunctional blood and lymphatic vessels (Nat Med 14: 255, 2008; PNAS 108: 18784, 2011). On the other hand, the promotion of endothelial NO production potentiates vascular normalization and improves concomitantly administered cytotoxic therapies (JNCI 105: 1188, 2013). We are currently studying perivascular NO gradient-induced vascular normalization from the following two angles – dissecting underlining mechanisms and establishing potential means of the improvement.

Role of tumor-host interactions in angiogenesis, tumor growth, metastasis and treatments: Using transgenic mice harboring the green fluorescent protein (GFP) gene driven by vascular endothelial growth factor (VEGF) promoter we found that VEGF promoter of non-transformed stromal cells is strongly activated by the tumor microenvironment (Cell 94: 715, 1998). Using tumor cells carrying the same gene construct we found, for the first time, that hypoxia and low pH independently upregulate VEGF in vivo (Cancer Res 61: 6248, 2001; J Biol Chem 277: 11368, 2002). Using VEGF-/- and wild type ES cell derived tumors we found that the host cells contribute approximately half of total VEGF production in this model (Cancer Res 60: 6248, 2000). MPLSM revealed that VEGF expressing stromal cells are closely associated with angiogenic vessel in the tumor (Nature Med 7: 864, 2001). The association of VEGF-expressing stromal cells spatially correlates with the extravasation of nanoparticles (Nature Med 11: 678, 2005). Furthermore, various anti-tumor treatments result in increased expression of host stromal cell VEGF and thus, may contribute to treatment resistance (Nature 416: 279, 2002; PNAS 109:E3119, 2012). In fact, judicious blockade of VEGF signaling can transiently normalize tumor vasculature and potentiate radiation therapy (Cancer Cell 6: 553, 2004; PNAS 108: 1799, 2011). Anti-VEGF treatments prolong survival of brain tumor bearing animals by normalizing the vasculature – reducing edema – (J Clin Oncol 27: 2542, 2009). However, ectopic expression of Angiopietin-2 compromises this benefit (Clin Cancer Res 16: 3618, 2010). On the other hand, platelet derived growth factor-D normalizes tumor vessels and improves delivery and efficacy of chemotherapeutics (Clin Cancer Res 17: 3638, 2011). In case of medulloblastoma, PlGF/NRP-1 signaling axis is the critical target (Cell 152: 1065, 2013). Finally, anti-VEGF treatment can restore immune microenvironment in tumors and potentiate vaccine therapy (PNAS 109:17561, 2012). We have been further dissecting mechanisms of tumor escape from anti-VEGF treatment focusing on inflammatory cells and pathways that can aggravate tumor growth, metastasis and response to treatment. Our recent data indicate that stromal cells in the primary tumor travel with tumor cells and facilitate survival and growth of metastatic tumors (PNAS 107: 21677, 2010). However, VEGFR1+ bone marrow derived cells (BMDCs) are not required for spontaneous metastasis (Nature 461: E4, 2009; PLoS One 4: e6525, 2009). We found that CXCR4 promotes metastasis via Gr-1+ BMDC recruitment (PNAS 108: 302, 2011). Finally, we found that metastatic tumors induce focal hyper-permeability in the lungs, leading to regional accumulation of inflammatory cytokines, and creating preferential sites of metastatic “soil” (PNAS 108: 3725, 2011).

Probing tumor microenvironment using nanotechnology: To dissect how the tumor microenvironment hinders delivery and efficacy of nanotherapeutics, and to develop strategies to overcome these barriers, we have been collaborating with MIT groups (Moungi Bawendi). We found that a “one size fits all” approach does not work for nanotherapeutics (Nat Nanotech 7: 383, 2012). I proposed and proved a provocative concept of multistage nanoparticle delivery system – a nanotherapeutic, which is optimal for transvascular transport, that reduces its size upon exposure to the tumor microenvironment for more efficient interstitial transport (PNAS 108: 2426, 2011).

Role of obesity in angiogenesis, tumor growth and treatments: As we have developed a strong interest in the link between angiogenesis and obesity, we established novel in vivo system to investigate adipogenesis and angiogenesis, simultaneously, in real time. Then, we discovered a provocative reciprocal regulation between adipogenesis and angiogenesis – adipogenesis induces angiogenesis while angiogenesis promotes adipocyte differentiation (Circ Res 93: e88, 2003). In a subsequent study, we showed an inhibition of diet-induced obesity by anti-angiogenic treatment. Obesity has been linked to poor treatment response in cancer patients including those receiving anti-angiogenic therapy. Using my expertise in vascular biology and anti-angiogenic therapy, we have been revealing the mechanisms of and strategies to overcome obesity-induced resistance to anti-angiogenic treatment.

Engineering blood vessels: My expertise and interest in angiogenesis and vessel maturation have been naturally transformed into a tissue-engineered blood vessel project. We first established methodologies for the generation of tissue engineered blood vessels and longitudinal monitoring of their formation and function in vivo (Nature 428: 138, 2004). Then, we evaluated various sources of human derived vascular cell progenitor/stem cells including human endothelial progenitor cells, embryonic stem cells and mesenchymal stem cells. Most recently, we successfully generated both endothelial cells and perivascular cells from human induced pluripotent stem (iPS) cells and ultimately their blood vessels in vivo (PNAS 110: 12774, 2013). This study opens a door to a variety of new research avenues including biology of de novo vascular formation, tissue engineering and potentially vascular disease models using patients-derived iPS cells.

Teaching responsibilities: Significant portion of my time has also been devoted to teaching tumor angiogenesis and microenviornment as well as various experimental techniques through daily supervision of research fellows and graduate students. My trainee are very successful as evidenced by their outstanding publications in Nature, Nature Biotechnology, Nature Medicine, Nature Methods, Journal of Clinical Investigation, Blood and Journal of Clinical Oncology as well as their awards from NIH, DOD, Howard Hughes Medical Institute, American Association for Cancer Research, Institute for Cancer Research, Susan Komen Foundation, Massachusetts Biomedical Research Corporation, Deutsche Forschungsgemeinschaft, La Ligue Nationnale Contre le Cancer, and Japanese Ministry of Health and Welfare. I also provide multiple lectures both in local and international courses and workshops.



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  • Lemon CM, Karnas E, Han X, Bruns OT, Kempa TJ, Fukumura D, Bawendi MG, Jain RK, Duda DG, Nocera DG. Micelle-Encapsulated Quantum Dot-Porphyrin Assemblies as in Vivo Two-Photon Oxygen Sensors. J Am Chem Soc 2015. PubMed
  • Ager EI, Kozin SV, Kirkpatrick ND, Seano G, Kodack DP, Askoxylakis V, Huang Y, Goel S, Snuderl M, Muzikansky A, Finkelstein DM, Dransfield DT, Devy L, Boucher Y, Fukumura D, Jain RK. Blockade of MMP14 activity in murine breast carcinomas: implications for macrophages, vessels, and radiotherapy. Journal of the National Cancer Institute 2015. PubMed
  • Stylianopoulos T, Economides EA, Baish JW, Fukumura D, Jain RK. Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors. Ann Biomed Eng 2015. PubMed
  • Han HS, Niemeyer E, Huang Y, Kamoun WS, Martin JD, Bhaumik J, Chen Y, Roberge S, Cui J, Martin MR, Fukumura D, Jain RK, Bawendi MG, Duda DG. Quantum dot/antibody conjugates for in vivo cytometric imaging in mice. Proc Natl Acad Sci U S A 2015; 112:1350-5. PubMed
  • Choi JW, Kim P, Kim JK, Kim YR, Fukumura D, Yun SH. Longitudinal Tracing of Spontaneous Regression and Anti-angiogenic Response of Individual Microadenomas during Colon Tumorigenesis. Theranostics 2015; 5:724-32. PubMed
  • Chen O, Riedemann L, Etoc F, Herrmann H, Coppey M, Barch M, Farrar CT, Zhao J, Bruns OT, Wei H, Guo P, Cui J, Jensen R, Chen Y, Harris DK, Cordero JM, Wang Z, Jasanoff A, Fukumura D, Reimer R, Dahan M, Jain RK, Bawendi MG. Magneto-fluorescent core-shell supernanoparticles. Nat Commun 2014; 5:5093. PubMed
  • Huang Y, Stylianopoulos T, Duda DG, Fukumura D, Jain RK. Benefits of vascular normalization are dose and time dependent--letter. Cancer Res 2013; 73:7144-6. PubMed
  • Goel S, Gupta N, Walcott BP, Snuderl M, Kesler CT, Kirkpatrick ND, Heishi T, Huang Y, Martin JD, Ager E, Samuel R, Wang S, Yazbek J, Vakoc BJ, Peterson RT, Padera TP, Duda DG, Fukumura D, Jain RK. Effects of vascular-endothelial protein tyrosine phosphatase inhibition on breast cancer vasculature and metastatic progression. Journal of the National Cancer Institute 2013; 105:1188-201. PubMed
  • Thunemann M, Wen L, Hillenbrand M, Vachaviolos A, Feil S, Ott T, Han X, Fukumura D, Jain RK, Russwurm M, de Wit C, Feil R. Transgenic mice for cGMP imaging. Circ Res 2013; 113:365-71. PubMed
  • Samuel R, Daheron L, Liao S, Vardam T, Kamoun WS, Batista A, Buecker C, Schäfer R, Han X, Au P, Scadden DT, Duda DG, Fukumura D, Jain RK. Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells. Proc Natl Acad Sci U S A 2013; 110:12774-9. PubMed
  • Jain RK, Munn LL, Fukumura D. Measuring interstitial pH and pO2 in mouse tumors. Cold Spring Harb Protoc 2013; 2013:675-7. PubMed
  • Jain RK, Munn LL, Fukumura D. Measuring interstitial diffusion, convection, and binding parameters in mouse tumors. Cold Spring Harb Protoc 2013; 2013:678-80. PubMed
  • Jain RK, Munn LL, Fukumura D. Measuring leukocyte-endothelial interactions in mice. Cold Spring Harb Protoc 2013; 2013:561-3. PubMed
  • Snuderl M, Batista A, Kirkpatrick ND, Ruiz de Almodovar C, Riedemann L, Walsh EC, Anolik R, Huang Y, Martin JD, Kamoun W, Knevels E, Schmidt T, Farrar CT, Vakoc BJ, Mohan N, Chung E, Roberge S, Peterson T, Bais C, Zhelyazkova BH, Yip S, Hasselblatt M, Rossig C, Niemeyer E, Ferrara N, Klagsbrun M, Duda DG, Fukumura D, Xu L, Carmeliet P, Jain RK. Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma. Cell 2013; 152:1065-76. PubMed
  • Huang Y, Goel S, Duda DG, Fukumura D, Jain RK. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res 2013. PubMed
  • Han HS, Martin JD, Lee J, Harris DK, Fukumura D, Jain RK, Bawendi M. Spatial charge configuration regulates nanoparticle transport and binding behavior in vivo. Angew Chem Int Ed Engl 2013; 52:1414-9. PubMed
  • Jain RK, Munn LL, Fukumura D. Measuring angiogenesis and hemodynamics in mice. Cold Spring Harb Protoc 2013. PubMed
  • Jain RK, Munn LL, Fukumura D. Lung window preparation in mice. Cold Spring Harb Protoc 2013. PubMed
  • Jain RK, Munn LL, Fukumura D. Pancreatic tumor preparation in mice. Cold Spring Harb Protoc 2012. PubMed
  • Jain RK, Munn LL, Fukumura D. Liver tumor preparation in mice. Cold Spring Harb Protoc 2012. PubMed
  • Kodack DP, Chung E, Yamashita H, Incio J, Duyverman AM, Song Y, Farrar CT, Huang Y, Ager E, Kamoun W, Goel S, Snuderl M, Lussiez A, Hiddingh L, Mahmood S, Tannous BA, Eichler AF, Fukumura D, Engelman JA, Jain RK. Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases. Proc Natl Acad Sci U S A 2012; 109:E3119-27. PubMed
  • Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, Santosuosso M, Martin JD, Martin MR, Vianello F, Leblanc P, Munn LL, Huang P, Duda DG, Fukumura D, Jain RK, Poznansky MC. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A 2012; 109:17561-6. PubMed
  • Jain RK, Munn LL, Fukumura D. Corneal pocket assay in rabbits. Cold Spring Harb Protoc 2012; 2012:1017-8. PubMed
  • Stylianopoulos T, Soteriou K, Fukumura D, Jain RK. Cationic Nanoparticles Have Superior Transvascular Flux into Solid Tumors: Insights from a Mathematical Model. Ann Biomed Eng 2012. PubMed
  • Jain RK, Munn LL, Fukumura D. Rabbit ear chambers. Cold Spring Harb Protoc 2012; 2012:813-14. PubMed
  • Chauhan VP, Stylianopoulos T, Martin JD, Popović Z, Chen O, Kamoun WS, Bawendi MG, Fukumura D, Jain RK. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat Nanotechnol 2012; 7:383-8. PubMed
  • Goel S, Fukumura D, Jain RK. Normalization of the tumor vasculature through oncogenic inhibition: an emerging paradigm in tumor biology. Proc Natl Acad Sci U S A 2012; 109:E1214. PubMed
  • Vakoc BJ, Fukumura D, Jain RK, Bouma BE. Cancer imaging by optical coherence tomography: preclinical progress and clinical potential. Nat Rev Cancer 2012; 12:363-8. PubMed
  • Jain RK, Munn LL, Fukumura D. Mammary fat pad chamber preparation in mice. Cold Spring Harb Protoc 2012. PubMed
  • Jain RK, Munn LL, Fukumura D. Lymphangiography of the mouse tail. Cold Spring Harb Protoc 2012. PubMed
  • Duyverman AM, Kohno M, Roberge S, Fukumura D, Duda DG, Jain RK. An isolated tumor perfusion model in mice. Nat Protoc 2012; 7:749-55. PubMed
  • Jain RK, Munn LL, Fukumura D. Lymphangiography of the mouse ear. Cold Spring Harb Protoc 2012. PubMed
  • Duyverman AM, Steller EJ, Fukumura D, Jain RK, Duda DG. Studying primary tumor-associated fibroblast involvement in cancer metastasis in mice. Nat Protoc 2012; 7:756-62. PubMed
  • Duyverman AM, Kohno M, Duda DG, Jain RK, Fukumura D. A transient parabiosis skin transplantation model in mice. Nat Protoc 2012; 7:763-70. PubMed
  • Jain RK, Munn LL, Fukumura D. Mammary fat pad tumor preparation in mice. Cold Spring Harb Protoc 2012. PubMed
  • Stylianopoulos T, Wong C, Bawendi MG, Jain RK, Fukumura D. Multistage nanoparticles for improved delivery into tumor tissue. Methods Enzymol 2012; 508:109-30. PubMed
  • Chauhan VP, Popović Z, Chen O, Cui J, Fukumura D, Bawendi MG, Jain RK. Fluorescent nanorods and nanospheres for real-time in vivo probing of nanoparticle shape-dependent tumor penetration. Angew Chem Int Ed Engl 2011; 50:11417-20. PubMed
  • Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP. Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci U S A 2011; 108:18784-9. PubMed
  • Cheng G, Liao S, Kit Wong H, Lacorre DA, di Tomaso E, Au P, Fukumura D, Jain RK, Munn LL. Engineered blood vessel networks connect to host vasculature via wrapping-and-tapping anastomosis. Blood 2011; 118:4740-9. PubMed
  • Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK. Normalization of the vasculature for treatment of cancer and other diseases. Physiol. Rev. 2011; 91:1071-121. PubMed
  • Liu J, Liao S, Huang Y, Samuel R, Shi T, Naxerova K, Huang P, Kamoun W, Jain RK, Fukumura D, Xu L. PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer. Clin Cancer Res 2011; 17:3638-48. PubMed
  • Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK. The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol 2011; 8:344-56. PubMed
  • Huang P, Westmoreland SV, Jain RK, Fukumura D. Spontaneous nonthymic tumors in SCID mice. Comp Med 2011; 61:227-34. PubMed
  • Hiratsuka S, Goel S, Kamoun WS, Maru Y, Fukumura D, Duda DG, Jain RK. Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation. Proc Natl Acad Sci U S A 2011; 108:3725-30. PubMed
  • Duda DG, Kozin S, Kirkpatrick ND, Xu L, Fukumura D, Jain RK. CXCL12 (SDF1α) - CXCR4/CXCR7 Pathway Inhibition: An Emerging Sensitizer for Anti-Cancer Therapies? Clin Cancer Res 2011. PubMed
  • Wong C, Stylianopoulos T, Cui J, Martin J, Chauhan VP, Jiang W, Popovic Z, Jain RK, Bawendi MG, Fukumura D. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc Natl Acad Sci U S A 2011; 108:2426-31. PubMed
  • Baish JW, Stylianopoulos T, Lanning RM, Kamoun WS, Fukumura D, Munn LL, Jain RK. Scaling rules for diffusive drug delivery in tumor and normal tissues. Proc Natl Acad Sci U S A 2011; 108:1799-803. PubMed
  • Hiratsuka S, Duda DG, Huang Y, Goel S, Sugiyama T, Nagasawa T, Fukumura D, Jain RK. C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells. Proc Natl Acad Sci U S A 2011; 108:302-7. PubMed
  • Duda DG, Duyverman AM, Kohno M, Snuderl M, Steller EJ, Fukumura D, Jain RK. Malignant cells facilitate lung metastasis by bringing their own soil. Proc Natl Acad Sci U S A 2010. PubMed
  • Popović Z, Liu W, Chauhan VP, Lee J, Wong C, Greytak AB, Insin N, Nocera DG, Fukumura D, Jain RK, Bawendi MG. A Nanoparticle Size Series for In Vivo Fluorescence Imaging. Angew Chem Int Ed Engl 2010; 49:8649-52. PubMed
  • Stylianopoulos T, Poh MZ, Insin N, Bawendi MG, Fukumura D, Munn LL, Jain RK. Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions. Biophys J 2010; 99:1342-9. PubMed
  • Brown E, Munn LL, Fukumura D, Jain RK. In vivo imaging of tumors. Cold Spring Harb Protoc 2010; 2010:pdb.prot5452. PubMed
  • Kamoun WS, Chae SS, Lacorre DA, Tyrrell JA, Mitre M, Gillissen MA, Fukumura D, Jain RK, Munn LL. Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networks. Nat Methods 2010; 7:655-60. PubMed
  • Chae SS, Kamoun WS, Farrar CT, Kirkpatrick ND, Niemeyer E, de Graaf AM, Sorensen AG, Munn LL, Jain RK, Fukumura D. Angiopoietin-2 Interferes with Anti-VEGFR-2- Induced Vessel Normalization and Survival Benefit in Mice Bearing Gliomas. Clin Cancer Res 2010; 16:3618-27. PubMed
  • Kim P, Chung E, Yamashita H, Hung KE, Mizoguchi A, Kucherlapati R, Fukumura D, Jain RK, Yun SH. In vivo wide-area cellular imaging by side-view endomicroscopy. Nat Methods 2010; 7:303-5. PubMed
  • Fukumura D, Duda DG, Munn LL, Jain RK. Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation 2010; 17:206-25. PubMed
  • Allen PM, Liu W, Chauhan VP, Lee J, Ting AY, Fukumura D, Jain RK, Bawendi MG. InAs(ZnCdS) quantum dots optimized for biological imaging in the near-infrared. J Am Chem Soc 2010; 132:470-1. PubMed
  • Liu W, Greytak AB, Lee J, Wong CR, Park J, Marshall LF, Jiang W, Curtin PN, Ting AY, Nocera DG, Fukumura D, Jain RK, Bawendi MG. Compact biocompatible quantum dots via RAFT-mediated synthesis of imidazole-based random copolymer ligand. J Am Chem Soc 2010; 132:472-83. PubMed
  • Vakoc BJ, Lanning RM, Tyrrell JA, Padera TP, Bartlett LA, Stylianopoulos T, Munn LL, Tearney GJ, Fukumura D, Jain RK, Bouma BE. Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat Med 2009; 15:1219-23. PubMed
  • Dawson MR, Duda DG, Fukumura D, Jain RK. VEGFR1-activity-independent metastasis formation. Nature 2009; 461:E4; discussion E5. PubMed
  • Kumar AT, Chung E, Raymond SB, van de Water JA, Shah K, Fukumura D, Jain RK, Bacskai BJ, Boas DA. Feasibility of in vivo imaging of fluorescent proteins using lifetime contrast. Opt Lett 2009; 34:2066-8. PubMed
  • Au P,Tam J,Duda DG,Lin PC,Munn LL,Fukumura D,Jain RK. Paradoxical Effects of PDGF-BB Overexpression in Endothelial Cells on Engineered Blood Vessels In Vivo. Am J Pathol 2009; 175:294-302. PubMed
  • Kamoun WS,Ley CD,Farrar CT,Duyverman AM,Lahdenranta J,Lacorre DA,Batchelor TT,di Tomaso E,Duda DG,Munn LL,Fukumura D,Sorensen AG,Jain RK. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J Clin Oncol 2009; 27:2542-52. PubMed
  • Luong MX,Tam J,Lin Q,Hagendoorn J,Moore KJ,Padera TP,Seed B,Fukumura D,Kucherlapati R,Jain RK. Lack of lymphatic vessel phenotype in LYVE-1/CD44 double knockout mice. J Cell Physiol 2009; 219:430-7. PubMed
  • Lahdenranta J,Hagendoorn J,Padera TP,Hoshida T,Nelson G,Kashiwagi S,Jain RK,Fukumura D. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis. Cancer Res 2009; 69:2801-8. PubMed
  • Tam J,Fukumura D,Jain RK. A mathematical model of murine metabolic regulation by leptin: energy balance and defense of a stable body weight. Cell Metab 2009; 9:52-63. PubMed
  • Chung E, Yamashita H, Au P, Tannous BA, Fukumura D, Jain RK. Secreted Gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases. PLoS ONE 2009; 4:e8316. PubMed
  • Dawson MR, Duda DG, Chae SS, Fukumura D, Jain RK. VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation. PLoS ONE 2009; 4:e6525. PubMed
  • Tam J,Duda DG,Perentes JY,Quadri RS,Fukumura D,Jain RK. Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: role of local versus bone marrow-derived endothelial cells. PLoS ONE 2009; 4:e4974. PubMed
  • Padera TP,Kuo AH,Hoshida T,Liao S,Lobo J,Kozak KR,Fukumura D,Jain RK. Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib. Mol Cancer Ther 2008; 7:2272-9. PubMed
  • Fukumura D,Jain RK. Imaging angiogenesis and the microenvironment. APMIS 2008; 116:695-715. PubMed
  • Huang P,Duda DG,Jain RK,Fukumura D. Histopathologic findings and establishment of novel tumor lines from spontaneous tumors in FVB/N mice. Comp Med 2008; 58:253-63. PubMed
  • Au P, Tam J, Fukumura D, Jain RK. Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood 2008; 111:4551-8. PubMed
  • Kashiwagi S, Tsukada K, Xu L, Miyazaki J, Kozin SV, Tyrrell JA, Sessa WC, Gerweck LE, Jain RK, Fukumura D. Perivascular nitric oxide gradients normalize tumor vasculature. Nat Med 2008; 14:255-7. PubMed
  • Au P, Daheron LM, Duda DG, Cohen KS, Tyrrell JA, Lanning RM, Fukumura D, Scadden DT, Jain RK. Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood 2007; 111:1302-5. PubMed
  • Jain RK, Lahdenranta J, Fukumura D. Targeting PDGF signaling in carcinoma-associated fibroblasts controls cervical cancer in mouse model. PLoS Med 2008; 5:e24. PubMed
  • Fukumura D, Jain RK. Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem 2007; 101:937-49. PubMed
  • Padera TP, Ancukiewicz M, Hoshida T, Fukumura D, Jain RK. Data Do Not Support Benefits of Anti-VEGFR3 Therapy. Cancer Res 2007; 67:5055. PubMed
  • Ogawa K, Boucher Y, Kashiwagi S, Fukumura D, Chen D, Gerweck LE. Influence of tumor cell and stroma sensitivity on tumor response to radiation. Cancer Res 2007; 67:4016-21. PubMed
  • Wang ZZ, Au P, Chen T, Shao Y, Daheron LM, Bai H, Arzigian M, Fukumura D, Jain RK, Scadden DT. Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol 2007; 25:317-8. PubMed
  • Au P, Tam J, Fukumura D, Jain RK. Small blood vessel engineering. Methods Mol. Med. 2007; 140:183-95. PubMed
  • Hoshida T, Isaka N, Hagendoorn J, di Tomaso E, Chen YL, Pytowski B, Fukumura D, Padera TP, Jain RK. Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: therapeutic implications. Cancer Res 2006; 66:8065-75. PubMed
  • Cochran DM, Fukumura D, Ancukiewicz M, Carmeliet P, Jain RK. Evolution of oxygen and glucose concentration profiles in a tissue-mimetic culture system of embryonic stem cells. Ann Biomed Eng 2006; 34:1247-58. PubMed
  • Fukumura D, Kashiwagi S, Jain RK. The role of nitric oxide in tumour progression. Nat Rev Cancer 2006; 6:521-34. PubMed
  • Xu L, Cochran DM, Tong RT, Winkler F, Kashiwagi S, Jain RK, Fukumura D. Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Res 2006; 66:3971-7. PubMed
  • Hagendoorn J, Tong R, Fukumura D, Lin Q, Lobo J, Padera TP, Xu L, Kucherlapati R, Jain RK. Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis. Cancer Res 2006; 66:3360-4. PubMed
  • Duda DG, Cohen KS, Kozin SV, Perentes JY, Fukumura D, Scadden DT, Jain RK. Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood 2005; 107:2774-6. PubMed
  • Acker T, Diez-Juan A, Aragones J, Tjwa M, Brusselmans K, Moons L, Fukumura D, Moreno-Murciano MP, Herbert JM, Burger A, Riedel J, Elvert G, Flamme I, Maxwell PH, Collen D, Dewerchin M, Jain RK, Plate KH, Carmeliet P. Genetic evidence for a tumor suppressor role of HIF-2alpha. Cancer Cell 2005; 8:131-41. PubMed
  • Jain RK,Au P,Tam J,Duda DG,Fukumura D. Engineering vascularized tissue. Nat Biotechnol 2005; 23:821-3. PubMed
  • Kashiwagi S, Izumi Y, Gohongi T, Demou ZN, Xu L, Huang PL, Buerk DG, Munn LL, Jain RK, Fukumura D. NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels. J Clin Invest 2005; 115:1816-27. PubMed
  • Hagendoorn J, Padera TP, Fukumura D, Jain RK. Molecular regulation of microlymphatic formation and function: role of nitric oxide. Trends Cardiovasc. Med. 2005; 15:169-73. PubMed
  • Huang P, McKee TD, Jain RK, Fukumura D. Green fluorescent protein (GFP)-expressing tumor model derived from a spontaneous osteosarcoma in a vascular endothelial growth factor (VEGF)-GFP transgenic mouse. Comp Med 2005; 55:236-43. PubMed
  • Stroh M, Zimmer JP, Duda DG, Levchenko TS, Cohen KS, Brown EB, Scadden DT, Torchilin VP, Bawendi MG, Fukumura D, Jain RK. Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat Med 2005; 11:678-82. PubMed
  • Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 2004; 6:553-63. PubMed
  • Duda DG,Fukumura D,Munn LL,Booth MF,Brown EB,Huang P,Seed B,Jain RK. Differential transplantability of tumor-associated stromal cells. Cancer Res 2004; 64:5920-4. PubMed
  • Hagendoorn J, Padera TP, Kashiwagi S, Isaka N, Noda F, Lin MI, Huang PL, Sessa WC, Fukumura D, Jain RK. Endothelial nitric oxide synthase regulates microlymphatic flow via collecting lymphatics. Circ Res 2004; 95:204-9. PubMed
  • Isaka N, Padera TP, Hagendoorn J, Fukumura D, Jain RK. Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function. Cancer Res 2004; 64:4400-4. PubMed
  • Gohongi T, Todoroki T, Fukumura D, Jain RK. Influence of the site of human gallbladder xenograft (Mz-ChA-1) on angiogenesis at the distant site. Oncol Rep 2004; 11:803-7. PubMed
  • Duda DG,Fukumura D,Jain RK. Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends Mol Med 2004; 10:143-5. PubMed
  • Koike N, Fukumura D, Gralla O, Au P, Schechner JS, Jain RK. Tissue engineering: creation of long-lasting blood vessels. Nature 2004; 428:138-9. PubMed
  • Xu L, Pathak PS, Fukumura D. Hypoxia-induced activation of p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase signaling pathways contributes to expression of interleukin 8 in human ovarian carcinoma cells. Clin Cancer Res 2004; 10:701-7. PubMed
  • Fukumura D,Ushiyama A,Duda DG,Xu L,Tam J,Krishna V,Chatterjee K,Garkavtsev I,Jain RK. Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis. Circ Res 2003; 93:e88-97. PubMed
  • Bockhorn M, Tsuzuki Y, Xu L, Frilling A, Broelsch CE, Fukumura D. Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts. Clin Cancer Res 2003; 9:4221-6. PubMed
  • Forbes NS, Munn LL, Fukumura D, Jain RK. Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors. Cancer Res 2003; 63:5188-93. PubMed
  • Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer 2003; 3:380-7. PubMed
  • Izumi Y, di Tomaso E, Hooper A, Huang P, Huber J, Hicklin DJ, Fukumura D, Jain RK, Suit HD. Responses to antiangiogenesis treatment of spontaneous autochthonous tumors and their isografts. Cancer Res 2003; 63:747-51. PubMed
  • Campbell RB, Fukumura D, Brown EB, Mazzola LM, Izumi Y, Jain RK, Torchilin VP, Munn LL. Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. Cancer Res 2002; 62:6831-6. PubMed
  • Dolmans DE, Kadambi A, Hill JS, Flores KR, Gerber JN, Walker JP, Borel Rinkes IH, Jain RK, Fukumura D. Targeting tumor vasculature and cancer cells in orthotopic breast tumor by fractionated photosensitizer dosing photodynamic therapy. Cancer Res 2002; 62:4289-94. PubMed
  • Dolmans DE, Kadambi A, Hill JS, Waters CA, Robinson BC, Walker JP, Fukumura D, Jain RK. Vascular accumulation of a novel photosensitizer, MV6401, causes selective thrombosis in tumor vessels after photodynamic therapy. Cancer Res 2002; 62:2151-6. PubMed
  • Monsky WL, Mouta Carreira C, Tsuzuki Y, Gohongi T, Fukumura D, Jain RK. Role of host microenvironment in angiogenesis and microvascular functions in human breast cancer xenografts: mammary fat pad versus cranial tumors. Clin Cancer Res 2002; 8:1008-13. PubMed
  • Jain RK, Munn LL, Fukumura D. Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer 2002; 2:266-76. PubMed
  • Xu L, Fukumura D, Jain RK. Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1/2 MAPK signaling pathway: mechanism of low pH-induced VEGF. J Biol Chem 2002; 277:11368-74. PubMed
  • Izumi Y, Xu L, di Tomaso E, Fukumura D, Jain RK. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002; 416:279-80. PubMed
  • Choi B, Bouma B, Fukumura D, Jain RK. Optical methods in vascular biology and medicine. J Biomed Opt 2010; 15:011001. PubMed
  • Fukumura D, Jain RK. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc Res 2007; 74:72-84. PubMed
  • Jain RK, Fukumura D, Duda DG. Lessons From 30 Years of Teaching About the Microenvironment of Tumors. Cancer J 2015; 21:137. PubMed