Christopher Dale Kontos | Scholars@Duke

Christopher Dale Kontos
Professor of Medicine

The Kontos Lab studies the molecular mechanisms of angiogenesis and vascular remodeling. Studies are directed toward understanding how signal transduction by endothelial receptor tyrosine kinase (RTKs) regulates vascular growth in both physiological and pathological processes, including exercise, peripheral artery disease (PAD), atherosclerosis, and cancer.

Current projects include:

1. Signal transduction, mechanisms of activation, and downregulation of endothelial RTKs (mainly Tie1, Tie2, VEGFR-1, and VEGFR-2)

2. Differential effects of the Angiopoietins

3. Role of the inositol phosphatase PTEN in the regulation of vascular cell growth and remodeling

4. PTEN gene therapy for prevention of vein graft disease

5. Angiogenic signaling in skeletal muscle, including mechanisms of exercise-induced angiogenesis

6. Proteolytic cleavage and shedding of endothelial RTKs

7. Angiogenic proteins as biomarkers in peripheral artery disease

Current Appointments & Affiliations

Professor of Medicine, Medicine, Cardiology, Medicine 2017
Director, Medical Scientist Training Program, Medicine, Cardiology, Medicine 2009
Professor of Pharmacology and Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 2017
Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 1993

Contact Information

180A CARL Bldg, 213 Research Dr., Durham, NC 27710
Duke Box 102148, Durham, NC 27710
cdkontos@duke.edu (919) 684-2119

Background
Education, Training, & Certifications
- Fellow in Cardiology, Medicine, Duke University 1993 - 1997
- M.D., Virginia Commonwealth University 1989
Previous Appointments & Affiliations
- Associate Professor of Medicine, Medicine, Cardiology, Medicine 2008 - 2017
- Associate Professor of Pharmacology & Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 2008 - 2017
- Assistant Professor in Pharmacology & Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 2001 - 2008
- Associate Professor of Medicine, Medicine, Cardiology, Medicine 2006 - 2008
- Assistant Professor of Medicine, Medicine, Cardiology, Medicine 1999 - 2006
- Associate in the Department of Medicine, Medicine, Cardiology, Medicine 1997 - 1999
- Instructor, Temporary in the Department of Medicine, Medicine, Cardiology, Medicine 1997
Recognition
In the News
- NOV 24, 2015
  
  Seven Faculty Named AAAS Fellows
Expertise
Global Scholarship
- Teaching
  - South Korea (Country)
Research
Selected Grants
- Medical Scientist Training Program awarded by National Institutes of Health 2022 - 2027
- Genetic Dissection of Angiogenesis in the Tuberculous Granuloma awarded by National Institutes of Health 2022 - 2027
- Cell and Molecular Biology Training Program awarded by National Institutes of Health 2021 - 2026
- Integrated Training in Anesthesiology Research awarded by National Institutes of Health 1996 - 2026
- Mechanisms Regulating Vascular Homeostasis awarded by National Institutes of Health 2021 - 2025
- Macrophage-Satellite Cell Interactions in the Ischemic Limb awarded by Vascular Cures 2021 - 2024
- Investigating the Metabolic Reprogramming of Ovarian Tumors During Omental Metastasis awarded by National Institutes of Health 2021 - 2024
- Printed Electronic Biosensors for Point-of-Care Testing of Cardiovascular Biomarkers awarded by National Institutes of Health 2019 - 2024
- Gertrude B. Elion Mentored Medical Student Award awarded by Triangle Community Foundation 2021 - 2023
- Gertrude B. Elion Mentored Medical Student Award awarded by Triangle Community Foundation 2021 - 2023
- Duke CTSA (TL1) Year 5 awarded by National Institutes of Health 2018 - 2023
- Variant Determinants of African American Limb Pathology in Peripheral Arterial Disease awarded by East Carolina University 2021 - 2023
- Multidisciplinary Heart and Vascular Diseases awarded by National Institutes of Health 1975 - 2023
- The Anti-angiogenic VEGF165b and VEGFR1 Signaling in Peripheral Artery Disease awarded by Augusta University 2019 - 2022
- U01 RPPR: Mitigators of Radiation-Induced Endovascular Injury: Targeting Tie2 and Thrombocytopenia awarded by National Institutes of Health 2017 - 2022
- Medical Scientist Training Program awarded by National Institutes of Health 1997 - 2022
- Duke Training Grant in Nephrology awarded by National Institutes of Health 1995 - 2022
- Gertrude B. Elion Mentored Medical Student Award awarded by Triangle Community Foundation 2019 - 2021
- TIE2 Activation for the Treatment of Chemical-Induced Acute Lung Injury awarded by National Institutes of Health 2017 - 2020
- Organization and Function of Cellular Structure awarded by National Institutes of Health 1975 - 2020
- Pharmacology Industry Internships for Ph.D. Students awarded by American Society for Pharmacology and Experimental Therapeutics 2017 - 2019
- Support for A Physician-Scientist Training Summit for MD-PhD and Post-Graduate Physician-Scientist Training Program Directors awarded by Burroughs Wellcome Fund 2019
- The Anti-angiogenic VEGF165b and VEGFR1 Signaling in Peripheral Artery Disease awarded by University of Virginia - Charlottesville 2018 - 2019
- A Novel Molecular Regulator of Vascular Homeostasis awarded by American Heart Association 2016 - 2019
- The role of muscle progenitor cells in muscle and vascular regeneration in PAD awarded by National Institutes of Health 2017 - 2019
- Gertrude Elion Mentored Medical Research Award awarded by Triangle Community Foundation 2018 - 2019
- Macrophages and Treatment-Resistant NVAMD awarded by National Institutes of Health 2015 - 2019
- Skeletal Muscle and Vascular Remodeling in Peripheral Artery Disease awarded by National Institutes of Health 2015 - 2018
- Seahorse XFe96 Extracellular Flux Analyzer awarded by North Carolina Biotechnology Center 2017 - 2018
- Enhancing dendritic cell migration to drive potent anti-tumor immune responses awarded by National Institutes of Health 2013 - 2017
- Tie2 Activation for the Treatment of Chemical-Induced Acute Lung Injury awarded by National Institutes of Health 2013 - 2016
- Muscle-Resident Stem Cells for Angiogenesis and Vascular Maturation in PAD awarded by National Institutes of Health 2013 - 2016
- Cancer Biology Training Grant awarded by National Cancer Institute 1993 - 2016
- Institutional Training Grant in Pediatric Cardiology awarded by National Institutes of Health 2009 - 2015
- Novel pathways modulating Raf-mediated cardiac hypertrophy awarded by National Institutes of Health 2013 - 2015
- The role of satellite cells in adult skeletal muscle growth and maintenance awarded by University of Kentucky 2013 - 2014
- Peripheral endothelial and muscle cell pathology in cardiovascular disease awarded by National Institutes of Health 2010 - 2013
- PTEN Gene Therapy for Vein Graft Disease awarded by National Institutes of Health 2009 - 2012
- The Role of PTEN in Endothelial Biology awarded by National Institutes of Health 2008 - 2012
- The Role of ADAM15 in sTie@ Shedding and Ischemic Angiogenesis awarded by National Institutes of Health 2009 - 2010
- Systems Biology of Angiogenesis awarded by National Institutes of Health 2006 - 2009
- Endothelial Cell Molecular Alterations in Cancer awarded by National Institutes of Health 2002 - 2008
- Therapeutic Angiogenesis for Erectile Dysfunction awarded by National Institutes of Health 2004 - 2008
- The Role of Tie2 and the Angiopoietins in EPC Biology awarded by National Institutes of Health 2005 - 2007
- Downregulation of Tie2 awarded by National Institutes of Health 2004 - 2007
- The Angiopoietins in Vascular Maintenance and Remodeling awarded by National Institutes of Health 2002 - 2007
- TIE2-Associated Molecular Targets in Tumor Vasculature awarded by National Institutes of Health 2002 - 2005
- Endothelial signal transduction by tek and tie awarded by National Institutes of Health 1997 - 2002
- same awarded by National Institutes of Health 1996 - 2002
- Endothelial Signal Transduction By Tek And Tie awarded by National Institutes of Health 1997 - 1999
- Tek Signaling And Endothelial Biology awarded by National Institutes of Health 1996 - 1999
External Relationships
- Guidepoint Global
- ICON Clinical Research Limited
- Merck Research Laboratories
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Zhang, Yu, Christopher D. Kontos, Brian H. Annex, and Aleksander S. Popel. “Endothelial Regulation of Microvascular Growth and Stability by Ang-Tie and VEGF Signaling Pathways: A Mechanistic Computational Systems Biology Model.” Faseb J 36 Suppl 1 (May 2022). https://doi.org/10.1096/fasebj.2022.36.S1.R2072.
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  - Gallagher, Emily J., Don C. Rockey, Christopher D. Kontos, Jatin M. Vyas, Lawrence F. Brass, Patrick J. Hu, Carlos M. Isales, et al. “Pearls of wisdom for aspiring physician-scientist residency applicants and program directors.” Jci Insight 7, no. 6 (March 22, 2022). https://doi.org/10.1172/jci.insight.158467.
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  - Zhang, Yu, Christopher D. Kontos, Brian H. Annex, and Aleksander S. Popel. “A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway.” Npj Syst Biol Appl 7, no. 1 (August 20, 2021): 34. https://doi.org/10.1038/s41540-021-00194-6.
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  - Permar, Sallie R., Rebecca A. Ward, Katherine J. Barrett, Stephanie A. Freel, Rasheed A. Gbadegesin, Christopher D. Kontos, Patrick J. Hu, Katherine E. Hartmann, Christopher S. Williams, and Jatin M. Vyas. “Addressing the physician-scientist pipeline: strategies to integrate research into clinical training programs.” J Clin Invest 130, no. 3 (March 2, 2020): 1058–61. https://doi.org/10.1172/JCI136181.
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  - Zhang, Yu, Christopher D. Kontos, Brian H. Annex, and Aleksander S. Popel. “Angiopoietin-Tie Signaling Pathway in Endothelial Cells: A Computational Model.” Iscience 20 (October 25, 2019): 497–511. https://doi.org/10.1016/j.isci.2019.10.006.
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  - Cheung, Joseph Y., Jennifer Gordon, JuFang Wang, Jianliang Song, Xue-Qian Zhang, Fabian Jana Prado, Santhanam Shanmughapriya, et al. “Mitochondrial dysfunction in human immunodeficiency virus-1 transgenic mouse cardiac myocytes.” J Cell Physiol 234, no. 4 (April 2019): 4432–44. https://doi.org/10.1002/jcp.27232.
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  - Myers, Valerie D., Glenn S. Gerhard, Dennis M. McNamara, Dhanendra Tomar, Muniswamy Madesh, Scott Kaniper, Frederick V. Ramsey, et al. “Association of Variants in BAG3 With Cardiomyopathy Outcomes in African American Individuals.” Jama Cardiol 3, no. 10 (October 1, 2018): 929–38. https://doi.org/10.1001/jamacardio.2018.2541.
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  - Myers, Valerie D., Dhanendra Tomar, Muniswamy Madesh, JuFang Wang, Jianliang Song, Xue-Qian Zhang, Manish K. Gupta, et al. “Haplo-insufficiency of Bcl2-associated athanogene 3 in mice results in progressive left ventricular dysfunction, β-adrenergic insensitivity, and increased apoptosis.” J Cell Physiol 233, no. 9 (September 2018): 6319–26. https://doi.org/10.1002/jcp.26482.
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  - Myers, Valerie D., Joseph M. McClung, JuFang Wang, Farzaneh G. Tahrir, Manish K. Gupta, Jennifer Gordon, Christopher H. Kontos, Kamel Khalili, Joseph Y. Cheung, and Arthur M. Feldman. “The Multifunctional Protein BAG3: A Novel Therapeutic Target in Cardiovascular Disease.” Jacc Basic Transl Sci 3, no. 1 (February 2018): 122–31. https://doi.org/10.1016/j.jacbts.2017.09.009.
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  - Tahrir, Farzaneh G., Santhanam Shanmughapriya, Taha Mohseni Ahooyi, Tijana Knezevic, Manish K. Gupta, Christopher D. Kontos, Joseph M. McClung, et al. “Dysregulation of mitochondrial bioenergetics and quality control by HIV-1 Tat in cardiomyocytes.” J Cell Physiol 233, no. 2 (February 2018): 748–58. https://doi.org/10.1002/jcp.26002.
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  - McClung, Joseph M., Timothy J. McCord, Terence E. Ryan, Cameron A. Schmidt, Tom D. Green, Kevin W. Southerland, Jessica L. Reinardy, et al. “BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.” Circulation 136, no. 3 (July 18, 2017): 281–96. https://doi.org/10.1161/CIRCULATIONAHA.116.024873.
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  - Feldman, Arthur M., Christopher D. Kontos, Joseph M. McClung, Glenn S. Gerhard, Kamel Khalili, and Joseph Y. Cheung. “Precision Medicine for Heart Failure: Lessons From Oncology.” Circ Heart Fail 10, no. 6 (June 2017). https://doi.org/10.1161/CIRCHEARTFAILURE.117.004202.
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  - Oehlers, Stefan H., Mark R. Cronan, Rebecca W. Beerman, Matthew G. Johnson, Jianhua Huang, Christopher D. Kontos, Jason E. Stout, and David M. Tobin. “Infection-Induced Vascular Permeability Aids Mycobacterial Growth.” J Infect Dis 215, no. 5 (March 1, 2017): 813–17. https://doi.org/10.1093/infdis/jiw355.
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  - Fujisawa, Takeshi, Keqing Wang, Xi-Lin Niu, Stuart Egginton, Shakil Ahmad, Peter Hewett, Christopher D. Kontos, and Asif Ahmed. “Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes.” Cardiovasc Res 113, no. 1 (January 2017): 81–89. https://doi.org/10.1093/cvr/cvw223.
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  - McClung, Joseph M., Timothy J. McCord, Kevin Southerland, Cameron A. Schmidt, Michael E. Padgett, Terence E. Ryan, and Christopher D. Kontos. “Subacute limb ischemia induces skeletal muscle injury in genetically susceptible mice independent of vascular density.” J Vasc Surg 64, no. 4 (October 2016): 1101-1111.e2. https://doi.org/10.1016/j.jvs.2015.06.139.
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  - Mueller, Sarah B., and Christopher D. Kontos. “Tie1: an orphan receptor provides context for angiopoietin-2/Tie2 signaling.” J Clin Invest 126, no. 9 (September 1, 2016): 3188–91. https://doi.org/10.1172/JCI89963.
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  - Padgett, Michael E., Timothy J. McCord, Joseph M. McClung, and Christopher D. Kontos. “Methods for Acute and Subacute Murine Hindlimb Ischemia.” J Vis Exp, no. 112 (June 21, 2016). https://doi.org/10.3791/54166.
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  - Mofarrahi, Mahroo, Joseph M. McClung, Christopher D. Kontos, Elaine C. Davis, Bassman Tappuni, Nicolay Moroz, Amy E. Pickett, et al. “Angiopoietin-1 enhances skeletal muscle regeneration in mice.” Am J Physiol Regul Integr Comp Physiol 308, no. 7 (April 1, 2015): R576–89. https://doi.org/10.1152/ajpregu.00267.2014.
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  - McClung, Joseph M., Jessica L. Reinardy, Sarah B. Mueller, Timothy J. McCord, Christopher D. Kontos, David A. Brown, Sabah N. A. Hussain, Cameron A. Schmidt, Terence E. Ryan, and Tom D. Green. “Muscle cell derived angiopoietin-1 contributes to both myogenesis and angiogenesis in the ischemic environment.” Front Physiol 6 (2015): 161. https://doi.org/10.3389/fphys.2015.00161.
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  - Reinardy, Jessica L., Daniel M. Corey, Christelle Golzio, Sarah B. Mueller, Nicholas Katsanis, and Christopher D. Kontos. “Phosphorylation of Threonine 794 on Tie1 by Rac1/PAK1 Reveals a Novel Angiogenesis Regulatory Pathway.” Plos One 10, no. 10 (2015): e0139614. https://doi.org/10.1371/journal.pone.0139614.
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  - Shen, Jikui, Maike Frye, Bonnie L. Lee, Jessica L. Reinardy, Joseph M. McClung, Kun Ding, Masashi Kojima, et al. “Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature.” J Clin Invest 124, no. 10 (October 2014): 4564–76. https://doi.org/10.1172/JCI74527.
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  - Kontos, Christopher D. “More than skin deep: connecting melanocyte pigmentation and angiogenic diseases.” J Clin Invest 124, no. 1 (January 2014): 76–79. https://doi.org/10.1172/JCI73559.
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  - Duscha, B. D., J. L. Robbins, C. D. Kontos, W. E. Kraus, and B. H. Annex. “Angiogenesis in peripheral artery disease: An emerging therapy targeting skeletal muscle,” December 1, 2013, 99–134.
  - Kontos, Christopher D., and Christopher G. Willett. “Inhibiting the inhibitor: targeting vascular endothelial protein tyrosine phosphatase to promote tumor vascular maturation.” J Natl Cancer Inst 105, no. 16 (August 21, 2013): 1163–65. https://doi.org/10.1093/jnci/djt199.
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  - Southerland, Kevin W., Sarah B. Frazier, Dawn E. Bowles, Carmelo A. Milano, and Christopher D. Kontos. “Gene therapy for the prevention of vein graft disease.” Transl Res 161, no. 4 (April 2013): 321–38. https://doi.org/10.1016/j.trsl.2012.12.003.
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  - Lee, Chang-Lung, Everett J. Moding, Kyle C. Cuneo, Yifan Li, Julie M. Sullivan, Lan Mao, Iman Washington, et al. “p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice.” Sci Signal 5, no. 234 (July 24, 2012): ra52. https://doi.org/10.1126/scisignal.2002918.
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  - McClung, Joseph M., Timothy J. McCord, Sehoon Keum, Soraya Johnson, Brian H. Annex, Douglas A. Marchuk, and Christopher D. Kontos. “Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice.” Am J Pathol 180, no. 5 (May 2012): 2156–69. https://doi.org/10.1016/j.ajpath.2012.01.032.
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  - Simnick, Andrew J., Miriam Amiram, Wenge Liu, Gabi Hanna, Mark W. Dewhirst, Christopher D. Kontos, and Ashutosh Chilkoti. “In vivo tumor targeting by a NGR-decorated micelle of a recombinant diblock copolypeptide.” J Control Release 155, no. 2 (October 30, 2011): 144–51. https://doi.org/10.1016/j.jconrel.2011.06.044.
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  - Chen, Long, Baoshan Xu, Lei Liu, Yan Luo, Hongyu Zhou, Wenxing Chen, Tao Shen, Xiuzhen Han, Christopher D. Kontos, and Shile Huang. “Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death.” Free Radic Biol Med 50, no. 5 (March 1, 2011): 624–32. https://doi.org/10.1016/j.freeradbiomed.2010.12.032.
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  - Wu, Florence T. H., Marianne O. Stefanini, Feilim Mac Gabhann, Christopher D. Kontos, Brian H. Annex, and Aleksander S. Popel. “VEGF and soluble VEGF receptor-1 (sFlt-1) distributions in peripheral arterial disease: an in silico model.” Am J Physiol Heart Circ Physiol 298, no. 6 (June 2010): H2174–91. https://doi.org/10.1152/ajpheart.00365.2009.
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  - Furgeson, Seth B., Peter A. Simpson, Insun Park, Vicki Vanputten, Henrick Horita, Christopher D. Kontos, Raphael A. Nemenoff, and Mary C. M. Weiser-Evans. “Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation.” Cardiovasc Res 86, no. 2 (May 1, 2010): 274–82. https://doi.org/10.1093/cvr/cvp425.
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  - Wu, Florence T. H., Marianne O. Stefanini, Feilim Mac Gabhann, Christopher D. Kontos, Brian H. Annex, and Aleksander S. Popel. “A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use.” J Cell Mol Med 14, no. 3 (March 2010): 528–52. https://doi.org/10.1111/j.1582-4934.2009.00941.x.
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  - Sagana, Rommel L., Mei Yan, Ashley M. Cornett, Jessica L. Tsui, David A. Stephenson, Steven K. Huang, Bethany B. Moore, et al. “Phosphatase and tensin homologue on chromosome 10 (PTEN) directs prostaglandin E2-mediated fibroblast responses via regulation of E prostanoid 2 receptor expression.” J Biol Chem 284, no. 47 (November 20, 2009): 32264–71. https://doi.org/10.1074/jbc.M109.004796.
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  - Ahmed, Asif, Takeshi Fujisawa, Xi-Lin Niu, Shakil Ahmad, Bahjat Al-Ani, Kunal Chudasama, Allyah Abbas, et al. “Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide.” Circ Res 104, no. 12 (June 19, 2009): 1333–36. https://doi.org/10.1161/CIRCRESAHA.109.196154.
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  - Wu, Florence T. H., Marianne O. Stefanini, Feilim Mac Gabhann, Christopher D. Kontos, Brian H. Annex, and Aleksander S. Popel. “Computational kinetic model of VEGF trapping by soluble VEGF receptor-1: effects of transendothelial and lymphatic macromolecular transport.” Physiol Genomics 38, no. 1 (June 10, 2009): 29–41. https://doi.org/10.1152/physiolgenomics.00031.2009.
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  - Lima, Brian, Gregory K. W. Lam, Liang Xie, Diana L. Diesen, Nestor Villamizar, Jeffrey Nienaber, Emily Messina, et al. “Endogenous S-nitrosothiols protect against myocardial injury.” Proc Natl Acad Sci U S A 106, no. 15 (April 14, 2009): 6297–6302. https://doi.org/10.1073/pnas.0901043106.
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  - Qiu, Wei, Lisa Federico, Mark Naples, Rita Kohen Avramoglu, Reza Meshkani, Jing Zhang, Julie Tsai, et al. “Phosphatase and tensin homolog (PTEN) regulates hepatic lipogenesis, microsomal triglyceride transfer protein, and the secretion of apolipoprotein B-containing lipoproteins.” Hepatology 48, no. 6 (December 2008): 1799–1809. https://doi.org/10.1002/hep.22565.
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  - Estrada, Rosendo, Qun Zeng, Hongwei Lu, Harshini Sarojini, Jen-Fu Lee, Steven P. Mathis, Teresa Sanchez, et al. “Up-regulating sphingosine 1-phosphate receptor-2 signaling impairs chemotactic, wound-healing, and morphogenetic responses in senescent endothelial cells.” J Biol Chem 283, no. 44 (October 31, 2008): 30363–75. https://doi.org/10.1074/jbc.M804392200.
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  - Xie, Donghua, Clarence M. Findley, Jason M. Greenfield, Anne M. Pippen, Christopher D. Kontos, Craig F. Donatucci, and Brian H. Annex. “A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits.” J Sex Med 5, no. 9 (September 2008): 2069–78. https://doi.org/10.1111/j.1743-6109.2008.00933.x.
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  - Findley, Clarence M., Robert G. Mitchell, Brian D. Duscha, Brian H. Annex, and Christopher D. Kontos. “Plasma levels of soluble Tie2 and vascular endothelial growth factor distinguish critical limb ischemia from intermittent claudication in patients with peripheral arterial disease.” J Am Coll Cardiol 52, no. 5 (July 29, 2008): 387–93. https://doi.org/10.1016/j.jacc.2008.02.045.
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  - Sarraf-Yazdi, Shiva, Jing Mi, Benjamin J. Moeller, Xilin Niu, Rebekah R. White, Christopher D. Kontos, Bruce A. Sullenger, Mark W. Dewhirst, and Bryan M. Clary. “Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer.” J Surg Res 146, no. 1 (May 1, 2008): 16–23. https://doi.org/10.1016/j.jss.2007.04.028.
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  - Xie, Donghua, Surovi Hazarika, Amy J. Andrich, Mike E. Padgett, Christopher D. Kontos, Craig F. Donatucci, and Brian H. Annex. “High cholesterol feeding in C57/Blc6 mice alters expression within the VEGF receptor-ligand family in corporal tissue.” J Sex Med 5, no. 5 (May 2008): 1137–48. https://doi.org/10.1111/j.1743-6109.2008.00801.x.
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  - Mi, Jing, Xiuwu Zhang, Zahid N. Rabbani, Yingmiao Liu, Srinevas K. Reddy, Zhen Su, Fawzia K. Salahuddin, et al. “RNA Aptamer-targeted Inhibition of NF-κB Suppresses Non-small Cell Lung Cancer Resistance to Doxorubicin.” Mol Ther 16, no. 1 (January 2008): 66–73. https://doi.org/10.1038/sj.mt.6300320.
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  - White, Rebekah R., Julie A. Roy, Kristi D. Viles, Bruce A. Sullenger, and Christopher D. Kontos. “A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function.” Angiogenesis 11, no. 4 (2008): 395–401. https://doi.org/10.1007/s10456-008-9122-4.
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  - Findley, Clarence M., Melissa J. Cudmore, Asif Ahmed, and Christopher D. Kontos. “VEGF induces Tie2 shedding via a phosphoinositide 3-kinase/Akt dependent pathway to modulate Tie2 signaling.” Arterioscler Thromb Vasc Biol 27, no. 12 (December 2007): 2619–26. https://doi.org/10.1161/ATVBAHA.107.150482.
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  - Hazarika, Surovi, Ayotunde O. Dokun, Yongjun Li, Aleksander S. Popel, Christopher D. Kontos, and Brian H. Annex. “Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1.” Circ Res 101, no. 9 (October 26, 2007): 948–56. https://doi.org/10.1161/CIRCRESAHA.107.160630.
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  - Cao, Yiting, Pierre Sonveaux, Shanling Liu, Yulin Zhao, Jing Mi, Bryan M. Clary, Chuan-Yuan Li, Christopher D. Kontos, and Mark W. Dewhirst. “Systemic overexpression of angiopoietin-2 promotes tumor microvessel regression and inhibits angiogenesis and tumor growth.” Cancer Res 67, no. 8 (April 15, 2007): 3835–44. https://doi.org/10.1158/0008-5472.CAN-06-4056.
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  - Kontos, Christopher D., and Brian H. Annex. “Engineered transcription factors for therapeutic angiogenesis.” Curr Opin Mol Ther 9, no. 2 (April 2007): 145–52.
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  - Li, Yongjun, Surovi Hazarika, Donghua Xie, Anne M. Pippen, Christopher D. Kontos, and Brian H. Annex. “In mice with type 2 diabetes, a vascular endothelial growth factor (VEGF)-activating transcription factor modulates VEGF signaling and induces therapeutic angiogenesis after hindlimb ischemia.” Diabetes 56, no. 3 (March 2007): 656–65. https://doi.org/10.2337/db06-0999.
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  - DeKroon, Robert, Jennifer B. Robinette, Anita B. Hjelmeland, Emma Wiggins, Morven Blackwell, Mirta Mihovilovic, Makoto Fujii, et al. “APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway via the phosphoinositol phosphatase SHIP2.” Circ Res 99, no. 8 (October 13, 2006): 829–36. https://doi.org/10.1161/01.RES.0000245479.03190.9f.
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  - Huang, Ning, Asim Khan, Homa Ashrafpour, Peter C. Neligan, Christopher R. Forrest, Christopher D. Kontos, and Cho Y. Pang. “Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability.” Am J Physiol Heart Circ Physiol 291, no. 1 (July 2006): H127–37. https://doi.org/10.1152/ajpheart.01253.2005.
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  - Xie, Donghua, Yongjun Li, Erika A. Reed, Shelley I. Odronic, Christopher D. Kontos, and Brian H. Annex. “An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb ischemia.” J Vasc Surg 44, no. 1 (July 2006): 166–75. https://doi.org/10.1016/j.jvs.2006.03.024.
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  - Mi, Jing, Shiva Sarraf-Yazdi, Xiuwu Zhang, Yiting Cao, Mark W. Dewhirst, Christopher D. Kontos, Chuan-Yuan Li, and Bryan M. Clary. “A comparison of antiangiogenic therapies for the prevention of liver metastases.” J Surg Res 131, no. 1 (March 2006): 97–104. https://doi.org/10.1016/j.jss.2005.09.008.
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  - White, Eric S., Rachelle G. Atrasz, Biao Hu, Sem H. Phan, Vuk Stambolic, Tak W. Mak, Cory M. Hogaboam, et al. “Negative regulation of myofibroblast differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on chromosome 10).” Am J Respir Crit Care Med 173, no. 1 (January 1, 2006): 112–21. https://doi.org/10.1164/rccm.200507-1058OC.
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  - Mi, Jing, Xiuwu Zhang, Zahid N. Rabbani, Yingmiao Liu, Zhen Su, Zeljko Vujaskovic, Christopher D. Kontos, Bruce A. Sullenger, and Bryan M. Clary. “H1 RNA polymerase III promoter-driven expression of an RNA aptamer leads to high-level inhibition of intracellular protein activity.” Nucleic Acids Res 34, no. 12 (2006): 3577–84. https://doi.org/10.1093/nar/gkl482.
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  - Hjelmeland, Anita B., Mark D. Hjelmeland, Qing Shi, Janet L. Hart, Darell D. Bigner, Xiao-Fan Wang, Christopher D. Kontos, and Jeremy N. Rich. “Loss of phosphatase and tensin homologue increases transforming growth factor beta-mediated invasion with enhanced SMAD3 transcriptional activity.” Cancer Res 65, no. 24 (December 15, 2005): 11276–81. https://doi.org/10.1158/0008-5472.CAN-05-3016.
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  - Xie, Donghua, Christopher D. Kontos, Craig F. Donatucci, and Brian H. Annex. “Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues.” J Sex Med 2, no. 5 (September 2005): 634–40. https://doi.org/10.1111/j.1743-6109.2005.00111.x.
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  - Liu, Songling, Richard T. Premont, Christopher D. Kontos, Shoukang Zhu, and Don C. Rockey. “A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension.” Nat Med 11, no. 9 (September 2005): 952–58. https://doi.org/10.1038/nm1289.
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  - Singh, Nirbhai, Elizabeth Macnamara, Saadia Rashid, Jayakrishna Ambati, Christopher D. Kontos, Eric Higgins, and Balamurali K. Ambati. “Systemic soluble Tie2 expression inhibits and regresses corneal neovascularization.” Biochem Biophys Res Commun 332, no. 1 (June 24, 2005): 194–99. https://doi.org/10.1016/j.bbrc.2005.04.108.
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  - Hata, Jonathan A., Jason A. Petrofski, Jacob N. Schroder, Matthew L. Williams, Sarah H. Timberlake, Anne Pippen, Michael T. Corwin, et al. “Modulation of phosphatidylinositol 3-kinase signaling reduces intimal hyperplasia in aortocoronary saphenous vein grafts.” J Thorac Cardiovasc Surg 129, no. 6 (June 2005): 1405–13. https://doi.org/10.1016/j.jtcvs.2004.11.048.
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  - Sanchez, Teresa, Shobha Thangada, Ming-Tao Wu, Christopher D. Kontos, Dianqing Wu, Hong Wu, and Timothy Hla. “PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.” Proc Natl Acad Sci U S A 102, no. 12 (March 22, 2005): 4312–17. https://doi.org/10.1073/pnas.0409784102.
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  - Huang, Jianhua, Xi-Lin Niu, Anne M. Pippen, Brian H. Annex, and Christopher D. Kontos. “Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia.” Arterioscler Thromb Vasc Biol 25, no. 2 (February 2005): 354–58. https://doi.org/10.1161/01.ATV.0000151619.54108.a5.
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  - Xie, D., C. D. Kontos, C. F. Donatucci, and B. H. Annex. “Erratum: Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues (Journal of Sexual Medicine (2005) 2 (634-640)).” Journal of Sexual Medicine 2, no. 6 (January 1, 2005): 876. https://doi.org/10.1111/j.1743-6109.2005.00154.x.
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  - Khan, Asim, Homa Ashrafpour, Ning Huang, Peter C. Neligan, Christopher Kontos, Anguo Zhong, Christopher R. Forrest, and Cho Y. Pang. “Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism.” Am J Physiol Regul Integr Comp Physiol 287, no. 5 (November 2004): R1219–29. https://doi.org/10.1152/ajpregu.00143.2004.
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  - Dai, Qunsheng, Jianhua Huang, Bruce Klitzman, Chunming Dong, Pascal J. Goldschmidt-Clermont, Keith L. March, Joseph Rokovich, et al. “Engineered zinc finger-activating vascular endothelial growth factor transcription factor plasmid DNA induces therapeutic angiogenesis in rabbits with hindlimb ischemia.” Circulation 110, no. 16 (October 19, 2004): 2467–75. https://doi.org/10.1161/01.CIR.0000145139.53840.49.
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  - Yamaoka-Tojo, Minako, Masuko Ushio-Fukai, Lula Hilenski, Sergey I. Dikalov, Yuqing E. Chen, Taiki Tojo, Tohru Fukai, et al. “IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species--dependent endothelial migration and proliferation.” Circ Res 95, no. 3 (August 6, 2004): 276–83. https://doi.org/10.1161/01.RES.0000136522.58649.60.
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  - Shan, Siqing, Nicole D. Robson, Yiting Cao, Tong Qiao, Chuan Y. Li, Christopher D. Kontos, Mariano Garcia-Blanco, and Mark W. Dewhirst. “Responses of vascular endothelial cells to angiogenic signaling are important for tumor cell survival.” Faseb J 18, no. 2 (February 2004): 326–28. https://doi.org/10.1096/fj.03-0765fje.
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  - Zadeh, Gelareh, Baoping Qian, Ali Okhowat, Nesrin Sabha, Christopher D. Kontos, and Abhijit Guha. “Targeting the Tie2/Tek receptor in astrocytomas.” Am J Pathol 164, no. 2 (February 2004): 467–76. https://doi.org/10.1016/S0002-9440(10)63137-9.
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  - Peters, Kevin G., Christopher D. Kontos, P Charles Lin, Adrianne L. Wong, Prema Rao, Liwen Huang, Mark W. Dewhirst, and Sabita Sankar. “Functional significance of Tie2 signaling in the adult vasculature.” Recent Prog Horm Res 59 (2004): 51–71. https://doi.org/10.1210/rp.59.1.51.
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  - Liu, Songling, Richard T. Premont, Christopher D. Kontos, Jianhua Huang, and Don C. Rockey. “Endothelin-1 activates endothelial cell nitric-oxide synthase via heterotrimeric G-protein betagamma subunit signaling to protein jinase B/Akt.” J Biol Chem 278, no. 50 (December 12, 2003): 49929–35. https://doi.org/10.1074/jbc.M306930200.
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  - Cai, Jun, Shakil Ahmad, Wen G. Jiang, Jianhua Huang, Christopher D. Kontos, Mike Boulton, and Asif Ahmed. “Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells.” Diabetes 52, no. 12 (December 2003): 2959–68. https://doi.org/10.2337/diabetes.52.12.2959.
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  - White, Rebekah R., Siqing Shan, Christopher P. Rusconi, Geetha Shetty, Mark W. Dewhirst, Christopher D. Kontos, and Bruce A. Sullenger. “Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.” Proc Natl Acad Sci U S A 100, no. 9 (April 29, 2003): 5028–33. https://doi.org/10.1073/pnas.0831159100.
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  - Niu, Xi-Lin, Kevin G. Peters, and Christopher D. Kontos. “Deletion of the carboxyl terminus of Tie2 enhances kinase activity, signaling, and function. Evidence for an autoinhibitory mechanism.” J Biol Chem 277, no. 35 (August 30, 2002): 31768–73. https://doi.org/10.1074/jbc.M203995200.
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  - Huang, Jianhua, and Christopher D. Kontos. “Inhibition of vascular smooth muscle cell proliferation, migration, and survival by the tumor suppressor protein PTEN.” Arterioscler Thromb Vasc Biol 22, no. 5 (May 1, 2002): 745–51. https://doi.org/10.1161/01.atv.0000016358.05294.8d.
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  - Huang, Jianhua, and Christopher D. Kontos. “PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects.” J Biol Chem 277, no. 13 (March 29, 2002): 10760–66. https://doi.org/10.1074/jbc.M110219200.
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  - Kontos, Christopher D., Eugene H. Cha, John D. York, and Kevin G. Peters. “The endothelial receptor tyrosine kinase Tie1 activates phosphatidylinositol 3-kinase and Akt to inhibit apoptosis.” Mol Cell Biol 22, no. 6 (March 2002): 1704–13. https://doi.org/10.1128/MCB.22.6.1704-1713.2002.
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  - Bussolati, B., C. Dunk, M. Grohman, C. D. Kontos, J. Mason, and A. Ahmed. “Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide.” Am J Pathol 159, no. 3 (September 2001): 993–1008. https://doi.org/10.1016/S0002-9440(10)61775-0.
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  - Huang, L., S. Sankar, C. Lin, C. D. Kontos, A. D. Schroff, E. H. Cha, S. M. Feng, et al. “HCPTPA, a protein tyrosine phosphatase that regulates vascular endothelial growth factor receptor-mediated signal transduction and biological activity.” J Biol Chem 274, no. 53 (December 31, 1999): 38183–88. https://doi.org/10.1074/jbc.274.53.38183.
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  - Kontos, C. D. “Inhibition of rat vascular smooth muscle cell proliferation in vitro and in vivo by recombinant replication-competent herpes simplex virus - Editorial Comment.” Stroke 30, no. 11 (November 1, 1999): 2438–39.
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  - Kontos, C. D., and B. H. Annex. “Angiogenesis.” Curr Atheroscler Rep 1, no. 2 (September 1999): 165–71. https://doi.org/10.1007/s11883-999-0013-y.
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  - Calvert, J. T., T. J. Riney, C. D. Kontos, E. H. Cha, V. G. Prieto, C. R. Shea, J. N. Berg, et al. “Allelic and locus heterogeneity in inherited venous malformations.” Hum Mol Genet 8, no. 7 (July 1999): 1279–89. https://doi.org/10.1093/hmg/8.7.1279.
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  - Kontos, C. D. “Adenovirus-mediated gene transfer is augmented in basilar and carotid arteries of heritable hyperlipidemic rabbits - Comment.” Stroke 30, no. 1 (January 1, 1999): 125–125.
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  - Kontos, C. D. “Expression of nerve growth factor and trkA after transient focal cerebral ischemia in rats - Comment.” Stroke 29, no. 8 (August 1, 1998): 1697–1697.
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  - Kontos, C. D., T. P. Stauffer, W. P. Yang, J. D. York, L. Huang, M. A. Blanar, T. Meyer, and K. G. Peters. “Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.” Mol Cell Biol 18, no. 7 (July 1998): 4131–40. https://doi.org/10.1128/MCB.18.7.4131.
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  - Peters, K. G., A. Coogan, D. Berry, J. Marks, J. D. Iglehart, C. D. Kontos, P. Rao, S. Sankar, and E. Trogan. “Expression of Tie2/Tek in breast tumour vasculature provides a new marker for evaluation of tumour angiogenesis.” Br J Cancer 77, no. 1 (1998): 51–56. https://doi.org/10.1038/bjc.1998.8.
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  - Kontos, C. D. “Intravenous basic fibroblast growth factor decreases brain injury resulting from focal ischemia in cats - Comment.” Stroke 28, no. 3 (March 1, 1997): 615–16.
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  - Kontos, C. D., E. P. Wei, J. I. Williams, H. A. Kontos, and J. T. Povlishock. “Cytochemical detection of superoxide in cerebral inflammation and ischemia in vivo.” Am J Physiol 263, no. 4 Pt 2 (October 1992): H1234–42. https://doi.org/10.1152/ajpheart.1992.263.4.H1234.
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- Book Sections
  - Mueller, S. B., and C. D. Kontos. “Gene Therapy for the Prevention of Vein Graft Disease.” In Translating Gene Therapy to the Clinic: Techniques and Approaches, 227–46, 2015. https://doi.org/10.1016/B978-0-12-800563-7.00015-4.
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  - Annex, B. H., and C. D. Kontos. “Angiogenesis and angiogenic growth factors as future therapies for cerebrovascular disease.” In Carotid Artery Stenosis: Current and Emerging Treatments, 181–96, 2005. https://doi.org/10.3109/9780203025970-27.
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