John Chappell, Ph.D.
- Cardiovascular engineering
Blood vessels deliver oxygen and distribute inflammatory cells to nearly every tissue in the human body, among other essential functions. Regulation of vascular growth must therefore be tightly controlled, and when this regulation is disrupted, numerous diseases can occur or become worsened such as cancer growth and metastasis. John Chappell and his research team study how the blood vasculature develops during early organ formation and during certain diseases such as tumor progression and neurological disorders. Increased insight into the basic mechanisms of blood vessel formation will guide the design of clinical therapies for vascular-related pathologies.
Pericytes are cells that wrap around blood vessels to maintain their stability and integrity. Disruptions in pericyte contribution to the vascular wall can lead to disease progression including diabetic retinopathy. Trained as a biomedical engineer, Chappell uses computational modeling approaches in conjunction with real-time imaging of ex vivo and in vitro models of blood vessel formation to understand pericyte behavior during blood vessel formation in health and disease. Understanding the mechanisms behind pericyte recruitment and investment will provide rationale and guidance for targeting pericyte-endothelial cell interactions for therapeutic benefit.
- University of North Carolina at Chapel Hill: Postdoctoral Research Associate, Program in Molecular Biology and Biotechnology Laboratory, 2014
- University of Virginia: Ph.D., Biomedical Engineering, 2007
- University of Virginia: M.S., Biomedical Engineering, 2005
- University of Virginia: B.S., Electrical Engineering, 2001
Awards, Honors and Services
- Outstanding Trainee Oral Presentation, UNC IVB/MHI Research Symposium, 2011
- Joseph S. Pagano Award for Best Paper by a Postdoctoral Fellow for 2009, First Place, 2010
- Keystone Symposia Conference on Angiogenesis in Health and Disease, Travel Scholarship, 2010
- Gordon Research Conference on Angiogenesis, Poster Presentation Award, 2009
- University of Virginia Engineering Research Symposium, First Place, 2007
- Virginia Nanotech Student Presentation Competition (Finalist), 2006
- Seven Society Graduate Fellowship for Superb Teaching (Finalist), 2002
Walpole J, Mac Gabhann F, Peirce SM, Chappell JC. Agent-based computational model of retinal angiogenesis simulates microvascular network morphology as a function of pericyte coverage. Microcirculation. 2017 Nov;24(8). doi:10.1111/micc.12393. PubMed PMID: 28791758; PubMed Central PMCID: PMC5673505.
Nesmith JE, Chappell JC, Cluceru JG, Bautch VL. Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis. Development. 2017 Mar 1;144(5):889-896. doi: 10.1242/dev.145672. PubMed PMID: 28246215; PubMed Central PMCID: PMC5374355.
Chappell JC, Cluceru JG, Nesmith JE, Mouillesseaux KP, Bradley VB, Hartland CM, Hashambhoy-Ramsay YL, Walpole J, Peirce SM, Mac Gabhann F, Bautch VL. Flt-1 (VEGFR-1) coordinates discrete stages of blood vessel formation. Cardiovasc Res. 2016 Jul 1;111(1):84-93. doi: 10.1093/cvr/cvw091. Epub 2016 May 3. PubMed PMID:27142980; PubMed Central PMCID: PMC4909163.
Walpole J, Chappell JC, Cluceru JG, Mac Gabhann F, Bautch VL, Peirce SM. Agent-based model of angiogenesis simulates capillary sprout initiation in multicellular networks. Integr Biol (Camb). 2015 Sep;7(9):987-97. doi:10.1039/c5ib00024f. Epub 2015 Jul 9. PubMed PMID: 26158406; PubMed Central PMCID:PMC4558383.
Chappell JC, Mouillesseaux KP, Bautch VL. Flt-1 (vascular endothelial growth factor receptor-1) is essential for the vascular endothelial growth factor-Notch feedback loop during angiogenesis. Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1952-9. doi: 10.1161/ATVBAHA.113.301805. Epub 2013 Jun 6. PubMed PMID:23744993; PubMed Central PMCID: PMC4521230.
Chappell JC, Taylor SM, Ferrara N, Bautch VL. Local guidance of emerging vessel sprouts requires soluble Flt-1. Dev Cell. 2009 Sep;17(3):377-86. doi:10.1016/j.devcel.2009.07.011. PubMed PMID: 19758562; PubMed Central PMCID:PMC2747120.
Chappell JC, Song J, Burke CW, Klibanov AL, Price RJ. Targeted delivery of nanoparticles bearing fibroblast growth factor-2 by ultrasonic microbubble destruction for therapeutic arteriogenesis. Small. 2008 Oct;4(10):1769-77. doi:10.1002/smll.200800806. PubMed PMID: 18720443; PubMed Central PMCID: PMC2716217.
Kappas NC, Zeng G, Chappell JC, Kearney JB, Hazarika S, Kallianos KG, Patterson C, Annex BH, Bautch VL. The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching. J Cell Biol. 2008 Jun 2;181(5):847-58. doi: 10.1083/jcb.200709114. Epub 2008 May 26. PubMed PMID:18504303; PubMed Central PMCID: PMC2396811.
Hashambhoy YL, Chappell JC, Peirce SM, Bautch VL, Mac Gabhann F. Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients. Front Physiol. 2011 Oct 4;2:62. doi: 10.3389/fphys.2011.00062. eCollection 2011. PubMed PMID: 22007175; PubMed Central PMCID: PMC3185289.
Chappell JC, Song J, Klibanov AL, Price RJ. Ultrasonic microbubble destruction stimulates therapeutic arteriogenesis via the CD18-dependent recruitment of bone marrow-derived cells. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1117-22. doi: 10.1161/ATVBAHA.108.165589. Epub 2008 Apr 10. PubMed PMID: 18403725.