Blood vessel development, angiogenesis, cancer, bioengineering, Microphysiological Systems (MPS), Tumor-on-chip
Growth of new blood vessels (angiogenesis) is an important process both in the healthy individual and in disease. Angiogenesis has become a hot area of research for cancer biologists as data suggest that blocking new blood vessel growth can slow tumor growth by cutting off the supply of oxygen and nutrients.
We have identified several genes involved in regulating the multiple steps of angiogenesis and are developing reagents to specifically interfere with these processes.
We have developed multi-cellular 3D tissues that are supported by perfused human vasculature. These tissues have been arrrayed to allow for high-throughput drug screening (HTS). We are developing several tissue-specific microphysiological systems (MPS), all supported by perfused vasculature. These inlcude brain, liver, pancreas (islets) and multiple tumor types. We are also developing modesl for HHT and Port Wine Birthmark (PWB/PWS) and Sturge-Weber Syndrome (SWS).
For more information see our website: https://faculty.sites.uci.edu/hugheslab/
Immunodeficient animal model for studying T cell-mediated immune responses
A high throughput platform comprising microtissues perfused with living microvessels
Keywords: Endothelial, vascular, angiogenesis, tissue engineering, high-throughput drug screening (HTS), 3D-tissues, tumor microenvironment
Professor Hughes is a faculty member in the Department of Molecular Biology and Biochemistry, and recently stepped down as chair after serving for 10 years. He is also a faculty member in Biomedical Engineering, and served for 5 years as Director of the Edwards Lifesciences Center for Advanced Cardiovascular Technology in the Henry Samueli School of Engineering. He also served for over ten years as co-director of the Onco-Imaging and Biotechnology Program, part of the Chao Family Comprehensive Cancer Center at UCI.
Professor Hughes’ research focuses on the development and growth of blood vessels. The work in his lab spans multiple scales – from understanding the basic molecular mechanisms of angiogenesis (the growth of new blood vessels), to engineering of artificial tissues. Recently his lab has been pioneering “Body-on-Chip” technology, which allows for micro-organs – heart, pancreas, tumor, etc. – to be grown in the lab, each with its own blood vessel network. These “Vascularized Micro-Organ” and “Vascularized Micro-Tumor” devices are set to revolutionize how we screen for new therapeutic drugs, and the technology is now licensed to Aracari Biosciences, of which Dr. Hughes is a founder, and for which he serves as CSO. Professor Hughes has published over 100 peer-reviewed research manuscripts, in some of the world’s top science journals. In recognition of his outstanding research and publication record, he was elected as a Fellow of the American Association for the Advancement of Science (AAAS) in 2014.
In addition to his research, Professor Hughes works extensively with the non-profit organization, cureHHT, which provides patient support and research advocacy on behalf of those suffering from the rare vascular disorder Hereditary Hemorrhagic Telangiectasia. Professor Hughes served for 8 years as Chair of the foundation’s Global Research and Medical Advisory Board and now chairs its North American Scientific and Medical Advisory Council.
Selected from > 100 (h-index = 63)
Hachey SJ, Movsesyan S, Nguyen QH, Burton-Sojo G, Tankanzyan A, Wu J, Hoang T, Hatch MM, Zhao D, Celaya E, Gomez S, Chen GT, Davis RT, Nee K, Pervolarakis N, Lawson DA, Kessenbrock K, Lee AP, Waterman ML, and Hughes CCW. 2021. An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy. Lab-on-a-Chip. doi: 10.1039/d0lc01216e. Online ahead of print.
Faughnan ME, Gossage JR, Chakinala MM, Oh SP, Kasthuri R, Hughes CCW, McWilliams JP, Parambil JG, Vozoris N, Donaldson J, Paul G, Berry P, and Sprecher D. 2019. Pazopanib may reduce bleeding in Hereditary Hemorrhagic Telangiectasia. Angiogenesis 22: 145-155
Hultgren NW, Fang JS, Ziegler ME, Ramirez RN, Phan DTT, Hatch MM, Welch-Reardon KM, Paniagua AE, Kim LS, Shon NN, Williams DS, Mortazavi A, and Hughes CCW. 2020. Slug Regulates the Dll4-Notch-VEGFR2 Axis to Control Endothelial Cell Activation and Angiogenesis. Nature Comm. 11: 5400.
Phan DT, Wang X, Craver BM, Sobrino A, Zhao D, Chen JC, Lee LY, George SC, Lee AP, and Hughes CCW. 2017. A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. Lab. Chip. 17: 511-520
Liu Y, Sakolish C, Chen Z, Phan DTT, Bender RHF, Hughes CCW, and Rusyn I. 2020. Human In Vitro Vascularized Micro-Organ and Micro-Tumor Models are Reproducible Organ-on-a-Chip Platforms for Studies of Anticancer Drugs. Toxicology 445: 152601
Romero-López M, Trinh AL, Sobrino A, Hatch MM, Keating MT, Fimbres C, Lewis DE, Gershon PD, Botvinick EL, Digman M, Lowengrub JS, and Hughes CCW. 2017. Recapitulating the human tumor microenvironment: Colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth. Biomaterials. 116: 118-129
Hachey SJ and Hughes CCW. 2018. Applications of tumor chip technology. Lab Chip. 2018 18: 2893-2912
Sobrino A, Phan DTT Datta R, Wang X, Hachey SJ, Romero-López M, Gratton E, Lee AP, George SC and Hughes CCW. 2016. 3D Microtumors in vitro supported by perfused vascular networks. Sci. Rep. 6: 31589
Fong AH, Romero-Lopez M, Heylman CM, Keating M, Tran D, Sobrino A, Tran AQ, Pham HH, Fimbres C, Gershon PD, Botvinick EL, George SC, and Hughes CCW. 2016. Three-dimensional adult cardiac extracellular matrix promotes maturation of human induced pluripotent stem cell-derived cardiomyocytes. Tissue Eng Part A 22(15-16): 1016-25
Ziegler ME, Hatch MMS, Wu N, Muawad S, and Hughes CCW. 2016. mTORC2 mediates SDF1?/CXCL12-induced angiogenesis. Angiogenesis 19(3): 359-71
Wang X, Phan DT, Sobrino A, George SC, Hughes CCW, Lee AP. 2016. Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels. Lab on a Chip 16 (2): 282-290
Popson SA, Ziegler ME, Chen X, Holderfield MT, Shaaban CI, Fong AH, Welch-Reardon KM, Papkoff J, and Hughes CCW. 2013. Interferon-induced transmembrane protein 1 regulates endothelial lumen formation during angiogenesis. Arterio. Thromb. Vasc. Biol. 34: 1011-19
Welch-Reardon KM, Ehsan SM, Wang K, Newman AC, Romero-Lopez M, Fong AH, George SC, Edwards RA, Hughes CCW. 2013 Angiogenic sprouting is regulated by endothelial cell expression of Slug (Snai2). J. Cell. Sci 127: 2017-2028
Ehsan SM, Welch-Reardon KM, Waterman ML, Hughes CCW, and George SC. 2013. A three-dimensional in vitro model of tumor angiogenesis and intravasation. Integrative Biology (in revision)
Heylman C, Sobrino A, Shirure VS, Hughes CCW, and George SC 2013. A strategy for integrating essential 3D microphysiological systems of human organs for realistic anti-cancer drug screening. Exp. Biol. Med. (in revision)
Hsu YH, Moya ML, Hughes CCW, George SC and Lee AP. 2013 microfluidic platform for generating large-scale nearly identical human microphysiological system arrays. Lab on a Chip 13: 2990-2998
Moya ML, Hsu, YH, Lee AP, Hughes CCW, and George SC. 2013. In vitro perfused human capillaries. Tissue Engineering 19: 730-737
Gong J, Archer R, Brown M, Fisher S, Chang C, Peacock MR, Hughes CCW, Freimark B. 2013 Measuring response to therapy by near-infrared imaging of tumors using a phosphatidylserine-targeting antibody fragment. Mol. Imaging 12: 244-56
Newman AC and Hughes CCW. 2012. Macrophages and angiogenesis: A role for wnt signaling. Vasc. Cell 4: 13-27
Newman AC, Chou W, Welch-Reardon KM, Fong AH, Popson SA, Phan DT, Sandoval DR, Gershon PD, and Hughes CCW. 2012. Analysis of stromal cell secretomes reveals a critical role for stromal cell-derived HGF and fibronectin in angiogenesis. Arterioscler. Thromb. Vasc. Biol. 33: 513-22.
Hsu YH, Moya ML, Abiri P, Hughes CCW, George SC, and Lee AP. 2012. Full range physiological mass transport control in 3D tissue cultures. Lab on a Chip 13: 81-89
White SM, Hingorania R, Aroraa R, Hughes CCW, George SC, and Choi B. 2012. Longitudinal in vivo imaging to assess vascularization of implantable engineered tissues. Tissue Eng. 18: 697-709
Kim J-H, George SC, and Hughes CCW. 2012. BMP9 induces EphrinB2 expression in endothelial cells through an Alk1-BMPRII/ActRII-ID1/ID3-dependent pathway: implications for hereditary hemorrhagic telangiectasia type II. Angiogenesis 15: 497-509
Newman AC, Nakatsu MN, Chou W, Gershon PD, and Hughes CCW. 2011 The requirement for fibroblasts in angiogenesis: fibroblast-derived matrix proteins are essential for endothelial cell lumen formation. Molecular Biology of the Cell. 22: 3791-800
Mestas J, and Hughes CCW. 2004. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172: 2731-2738
PI on UH3.
MPI on R61
MPI on UG3.
PI on T32.
Co-I on 4 RO1s.
Co-I on U54.
North American Vascular Biology Organization
American Society for Investigative Pathology
Aracari Biosciences 2019—cur.
Chair, cureHHT Scientific and Medical Advisory Council
cureHHT (rare disease charity) 2019—cur.
Cancer Research Institute
Edwards Lifesciences Center for Advanced Cardiovascular Technology