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Ping Nian He, Ph.D.

TitleProfessor
InstitutionCollege of Medicine
DepartmentCellular and Molecular Physiology
Address500 University Drive Hershey, PA 17033
Phone717-531-3596
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    Collapse Overview 
    Collapse overview
    PREFERRED TITLE/ROLE:

    Professor of Cellular and Molecular Physiology

    GRADUATE PROGRAM AFFILIATIONS:

    Biomedical Sciences

    EDUCATION:

    M.D., Tianjin Medical University, Tianjin, China, 1982

    Residency, Neurology, Tianjin Medical University, Tianjin, China, 1984

    Ph.D. University of California, Davis, 1990

    Postdoctoral Training, University of California, Davis, 1990-1992

    NARRATIVE:

    Accumulated clinical and experimental evidence indicate that the inflammation-associated increases in vascular permeability is the initiating event or consequences for a variety of cardiovascular diseases. A better understanding of the mechanisms that regulate microvessel permeability is crucial to defining the pathogenesis of many disease conditions and aiding the development of novel therapeutic approaches. Over the past 20 years, our research has been focused on the identification of the cellular and molecular mechanisms and transport pathways contributing to the permeability increases under acute and chronic inflammatory conditions. The unique experimental approach that commonly used in the laboratory is to investigate the cellular and molecular mechanisms using individually perfused intact microvessels from anesthetized animals with intact surrounding circulation. This technique allows us to quantitatively measure microvessel permeability coefficients, endothelial cell signaling, and correlate them with vascular wall structural changes at cellular and molecular levels using both conventional and confocal fluorescence imaging in combination with electron microscopic studies. The results derived from our studies have served as a bridge between in vitro and whole organ or whole animal studies. Since our experimental conditions closely mimic the in vivo environment, we are currently at the best position to develop clinically relevant and translational research projects and link animal studies with patient conditions. Our single vessel perfusion approach also provides the most relevant in vivo validation for the development of biomedical devices such as microfluidics or organ on chip projects, and has a great potential to apply nanotechnology to the therapeutic development and mechanistic studies for transport and drug delivery.

    DESCRIPTION OF RESEARCH:

    1) The mechanisms involved in diabetes-associated microvascular complications with focus on the roles of increased circulating microparticles in the development of microvascular dysfunction.

    2) The impact of changing blood flow, i.e. mechanical forces, on endothelial cell signaling and microvascular barrier function and how pathologically impaired glycocalyx affects endothelial cell sensing shear stress and vascular barrier function under diabetic/obese conditions.

    3) The mechanisms of ROS-induced microvascular complications and the interplay of ROS with nitric oxide and reactive nitrogen species in the regulation of microvessel permeability under pathological conditions.

    4) Developing engineered microvessels using a fluid platform to simulate key features of the microvessels in vivo and applying them to human tissue related biomedical research.

    5) The roles of tumor cell-derived cytokine-mediated permeability increases in tumor metastasis.

    6) The roles of tumor cell-derived microparticles in the tumor progression and metastasis.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Gao F, Lucke-Wold BP, Li X, Logsdon AF, Xu LC, Xu S, LaPenna KB, Wang H, Talukder MAH, Siedlecki CA, Huber JD, Rosen CL, He P. Reduction of Endothelial Nitric Oxide Increases the Adhesiveness of Constitutive Endothelial Membrane ICAM-1 through Src-Mediated Phosphorylation. Front Physiol. 2017; 8:1124. PMID: 29367846.
      View in: PubMed
    2. Begum G, Song S, Wang S, Zhao H, Bhuiyan MIH, Li E, Nepomuceno R, Ye Q, Sun M, Calderon MJ, Stolz DB, St Croix C, Watkins SC, Chen Y, He P, Shull GE, Sun D. Selective knockout of astrocytic Na+ /H+ exchanger isoform 1 reduces astrogliosis, BBB damage, infarction, and improves neurological function after ischemic stroke. Glia. 2018 Jan; 66(1):126-144. PMID: 28925083.
      View in: PubMed
    3. Dang TQ, Yoon N, Chasiotis H, Dunford EC, Feng Q, He P, Riddell MC, Kelly SP, Sweeney G. Transendothelial movement of adiponectin is restricted by glucocorticoids. J Endocrinol. 2017 Aug; 234(2):101-114. PMID: 28705835.
      View in: PubMed
    4. Xu S, Li X, LaPenna KB, Yokota SD, Huke S, He P. New insights into shear stress-induced endothelial signalling and barrier function: cell-free fluid versus blood flow. Cardiovasc Res. 2017 Apr 01; 113(5):508-518. PMID: 28158679.
      View in: PubMed
    5. Xu S, Li X, Liu Y, He P. Development and Characterization of In Vitro Microvessel Network and Quantitative Measurements of Endothelial [Ca2+]i and Nitric Oxide Production. J Vis Exp. 2016 May 19; (111). PMID: 27286521.
      View in: PubMed
    6. Park K, Mima A, Li Q, Rask-Madsen C, He P, Mizutani K, Katagiri S, Maeda Y, Wu IH, Khamaisi M, Preil SR, Maddaloni E, Sørensen D, Rasmussen LM, Huang PL, King GL. Insulin decreases atherosclerosis by inducing endothelin receptor B expression. JCI Insight. 2016 May 05; 1(6). PMID: 27200419.
      View in: PubMed
    7. Li X, Xu S, He P, Liu Y. In vitro recapitulation of functional microvessels for the study of endothelial shear response, nitric oxide and [Ca2+]i. PLoS One. 2015; 10(5):e0126797. PMID: 25965067; PMCID: PMC4429116.
    8. Yuan D, Xu S, He P. Enhanced permeability responses to inflammation in streptozotocin-induced diabetic rat venules: Rho-mediated alterations of actin cytoskeleton and VE-cadherin. Am J Physiol Heart Circ Physiol. 2014 Jul 01; 307(1):H44-53. PMID: 24778164; PMCID: PMC4080175.
    9. Xu S, Zhou X, Yuan D, Xu Y, He P. Caveolin-1 scaffolding domain promotes leukocyte adhesion by reduced basal endothelial nitric oxide-mediated ICAM-1 phosphorylation in rat mesenteric venules. Am J Physiol Heart Circ Physiol. 2013 Nov 15; 305(10):H1484-93. PMID: 24043249; PMCID: PMC3840264.
    10. Zhou X, Yuan D, Wang M, He P. H2O2-induced endothelial NO production contributes to vascular cell apoptosis and increased permeability in rat venules. Am J Physiol Heart Circ Physiol. 2013 Jan 01; 304(1):H82-93. PMID: 23086988; PMCID: PMC3543683.
    11. Yuan D, He P. Vascular remodeling alters adhesion protein and cytoskeleton reactions to inflammatory stimuli resulting in enhanced permeability increases in rat venules. J Appl Physiol (1985). 2012 Oct; 113(7):1110-20. PMID: 22837164; PMCID: PMC3487498.
    12. Zhou X, He P. Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial [Ca²?]i, nitric oxide, and gap formation in intact venules. Am J Physiol Heart Circ Physiol. 2011 Nov; 301(5):H1788-97. PMID: 21873500; PMCID: PMC3213973.
    13. Zhou X, He P. Improved measurements of intracellular nitric oxide in intact microvessels using 4,5-diaminofluorescein diacetate. Am J Physiol Heart Circ Physiol. 2011 Jul; 301(1):H108-14. PMID: 21536843; PMCID: PMC3129913.
    14. Zhang G, Xu S, Qian Y, He P. Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules. Am J Physiol Heart Circ Physiol. 2010 Nov; 299(5):H1494-504. PMID: 20729401; PMCID: PMC2993214.
    15. He P. Leucocyte/endothelium interactions and microvessel permeability: coupled or uncoupled? Cardiovasc Res. 2010 Jul 15; 87(2):281-90. PMID: 20472564; PMCID: PMC2895544.
    16. Zhou X, He P. Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules. Cardiovasc Res. 2010 Jul 15; 87(2):340-7. PMID: 20080986; PMCID: PMC2895537.
    17. He P. Beyond tie-ing up endothelial adhesion: new insights into the action of angiopoietin-1 in regulation of microvessel permeability. Cardiovasc Res. 2009 Jul 01; 83(1):1-2. PMID: 19429667.
      View in: PubMed
    18. Zhou X, Wen K, Yuan D, Ai L, He P. Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability. Am J Physiol Heart Circ Physiol. 2009 Apr; 296(4):H1096-107. PMID: 19201997; PMCID: PMC2670695.
    19. Zhou X, Miller MR, Motaleb M, Charon NW, He P. Spent culture medium from virulent Borrelia burgdorferi increases permeability of individually perfused microvessels of rat mesentery. PLoS One. 2008; 3(12):e4101. PMID: 19116656; PMCID: PMC2605548.
    20. Jiang Y, Wen K, Zhou X, Schwegler-Berry D, Castranova V, He P. Three-dimensional localization and quantification of PAF-induced gap formation in intact venular microvessels. Am J Physiol Heart Circ Physiol. 2008 Aug; 295(2):H898-906. PMID: 18515648; PMCID: PMC2519217.
    21. He P, Zhang H, Zhu L, Jiang Y, Zhou X. Leukocyte-platelet aggregate adhesion and vascular permeability in intact microvessels: role of activated endothelial cells. Am J Physiol Heart Circ Physiol. 2006 Aug; 291(2):H591-9. PMID: 16517944.
      View in: PubMed
    22. Zhu L, He P. fMLP-stimulated release of reactive oxygen species from adherent leukocytes increases microvessel permeability. Am J Physiol Heart Circ Physiol. 2006 Jan; 290(1):H365-72. PMID: 16155097.
      View in: PubMed
    23. Minnear FL, Zhu L, He P. Sphingosine 1-phosphate prevents platelet-activating factor-induced increase in hydraulic conductivity in rat mesenteric venules: pertussis toxin sensitive. Am J Physiol Heart Circ Physiol. 2005 Aug; 289(2):H840-4. PMID: 15778280.
      View in: PubMed
    24. Zhu L, He P. Platelet-activating factor increases endothelial [Ca2+]i and NO production in individually perfused intact microvessels. Am J Physiol Heart Circ Physiol. 2005 Jun; 288(6):H2869-77. PMID: 15665052.
      View in: PubMed
    25. Bernatchez PN, Bauer PM, Yu J, Prendergast JS, He P, Sessa WC. Dissecting the molecular control of endothelial NO synthase by caveolin-1 using cell-permeable peptides. Proc Natl Acad Sci U S A. 2005 Jan 18; 102(3):761-6. PMID: 15637154; PMCID: PMC545535.
    26. Zhu L, Castranova V, He P. fMLP-stimulated neutrophils increase endothelial [Ca2+]i and microvessel permeability in the absence of adhesion: role of reactive oxygen species. Am J Physiol Heart Circ Physiol. 2005 Mar; 288(3):H1331-8. PMID: 15498822.
      View in: PubMed
    27. Zhu L, Schwegler-Berry D, Castranova V, He P. Internalization of caveolin-1 scaffolding domain facilitated by Antennapedia homeodomain attenuates PAF-induced increase in microvessel permeability. Am J Physiol Heart Circ Physiol. 2004 Jan; 286(1):H195-201. PMID: 12946927.
      View in: PubMed
    28. Zeng M, Zhang H, Lowell C, He P. Tumor necrosis factor-alpha-induced leukocyte adhesion and microvessel permeability. Am J Physiol Heart Circ Physiol. 2002 Dec; 283(6):H2420-30. PMID: 12388263.
      View in: PubMed
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