Center for Matrix Biology - Vanderbilt University and Medical Center

P. Charles Lin, Ph.D.
Associate Professor in the Department of Radiation Oncology

	Office Address:	712 Preston Research Building
	Mailing Address:	712 Preston Research Building Nashville, TN 6300
	Lab address:	712 Preston Research Building
	Phone:	615-936-1749
		email

Secondary appointment in the Cell and Developmental Biology department.
Secondary appointment in the Cancer Biology department.

Research Summary

Research in our laboratory centers on the mechanisms that govern blood vessel formation (Research in our laboratory centers on the mechanisms that govern blood vessel formation (angiogenesis). Vascular networks form to satisfy the metabolic demands of tissue growth during development. When we reach adulthood, the vascular endothelium becomes quiescent. However, under disease conditions, this delicate balance is disturbed and endothelium is reactivated. Since the disease development often involves tissue growth, regeneration and repair. It is not a surprise that the majority of human diseases directly link to abnormal angiogenesis, either with excessive angiogenesis (e.g. cancer) or insufficient angiogenesis (e.g. heart ischemia due to clotted blood vessels). We are interested in dissecting signaling pathways and understanding the biology in angiogenesis. Whenever possible, we aim our research towards developing therapeutic strategies to either inhibit angiogenesis in tumors or enhance angiogenesis in ischemic heart.

Current research projects include: 1) vascular stability and vascular survival. We are interested in the interaction of VEGFR and Tie2 signaling in vascular formation, maturation and survival. This information will help us establishing new strategies to induce tumor vascular apoptosis and tumor regression. 2) Immune suppression and angiogenesis. Recently, we found that immature myeloid cells induced in cancer hosts cause immune suppression and tumor angiogenesis, two essential steps in tumor progression. Currently, we investigate the molecular mechanisms that control production, recruitment to tumors and differentiation of these cells. 3) Endothelium-to-mesenchymal transformation (EMT). The endothelium undergoes EMT during angiogenesis and cardiovascular formation. Using three-dimensional organ culture systems and transgenic mice, we are investigating the novel role of Akt and NF-κB in EMT during angiogenesis, and cardiac valve formation. 4) Inflammation and angiogenesis. The major difference between physiological and pathological angiogenesis is inflammation. Using arthritis as a model system, we are studying angiogenic gene regulation in response to inflammatory cytokines, the interaction between endothelial cells and synoviocytes during disease development.

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Associated initiative(s):

Angiogenesis

Tissue Regeneration

Tumor Microenvironment

Career opportunities:
Postdoctoral Position Available

Selected Publications

» Kobayashi, H, Lin, PC Angiogenesis links chronic inflammation with cancer Methods Mol Biol 2009. 511:185-91

» Kobayashi, H, Lin, PC Molecular characterization of IL-32 in human endothelial cells Cytokine 2009. 46:351-8

» Laura M DeBusk, Kimberly Boelte, Yongfen Min and P. Charles Lin. Haploinsufficiency of I'-catenin regulates pathlogical angiogenesis. Journal of Experimental Medicine 2009. in press:

» Kobayashi, H, Yazlovitskaya, EM, Lin, PC Interleukin-32 positively regulates radiation-induced vascular inflammation Int J Radiat Oncol Biol Phys 2009. 74:1573-9

» DeBusk, LM, Massion, PP, Lin, PC IkappaB kinase-alpha regulates endothelial cell motility and tumor angiogenesis Cancer Res 2008. 68:10223-8

» Yang, L, Huang, J, Ren, X, Gorska, AE, Chytil, A, Aakre, M, Carbone, DP, Matrisian, LM, Richmond, A, Lin, PC, Moses, HL Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis Cancer Cell 2008. 13:23-35

» Yankeelov, TE, Luci, JJ, DeBusk, LM, Lin, PC, Gore, JC Incorporating the effects of transcytolemmal water exchange in a reference region model for DCE-MRI analysis: theory, simulations, and experimental results Magn Reson Med 2008. 59:326-35

» Hanako Kobayashi, Laura M. DeBusk and P. Charles Lin Angiopoietin/Tie2 signaling regulates tumor angiogenesis Antiangiogenic cancer therapy. Edited by Lee Ellis and Beverly Teicher 2007. :

» Kobayashi, H, Boelte, KC, Lin, PC Endothelial cell adhesion molecules and cancer progression Curr Med Chem 2007. 14:377-86

» Kobayashi, H, Lin, PC Nanotechnology for antiangiogenic cancer therapy Nanomed 2006. 1:17-22

» Yankeelov, TE, DeBusk, LM, Billheimer, DD, Luci, JJ, Lin, PC, Price, RR, Gore, JC Repeatability of a reference region model for analysis of murine DCE-MRI data at 7T J Magn Reson Imaging 2006. 24:1140-7

» Kobayashi, H, DeBusk, LM, Babichev, YO, Dumont, DJ, Lin, PC Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell recruitment Blood 2006. 108:1260-6

» Kobayashi, H, Lin, PC Antiangiogenic and radiotherapy for cancer treatment Histol Histopathol 2006. 21:1125-34

» Hanako Kobayashi and P. Charles Lin Nanotechnology for antiangiogenic cancer therapy Nanomedicine 2006. 1:17

» Jinpu Yu, Xiubao Ren, Shui Cao, Weihong Zhang, P. Charles Lin and Xishan Hao Th1 polarization and apoptosis-inducing activity of CD4+ T cells in CIKs might favor the antitumor cytotoxicity of CIKs in vivo Cancer Biotherapy and Radiopharmacy 2006. in press:

» Kamiyama, M, Pozzi, A, Yang, L, Debusk, LM, Breyer, RM, Lin, PC EP2, a receptor for PGE(2), regulates tumor angiogenesis through direct effects on endothelial cell motility and survival Oncogene 2006. 25:7019-28

» Hanako Kobayashi and P. Charles Lin Antiangiogenic therapy and radiotherapy for cancer Histology and Histopathology 2006. 21:1125

» Kobayashi, Hanako, Lin, P Charles Angiopoietin/Tie2 signaling, tumor angiogenesis and inflammatory diseases Front Biosci 2005. 10:666-74

» Chen, Y, Donnelly, E, Kobayashi, H, Debusk, LM, Lin, PC Gene therapy targeting the Tie2 function ameliorates collagen-induced arthritis and protects against bone destruction Arthritis Rheum 2005. 52:1585-94

» Yankeelov, TE, Luci, JJ, Lepage, M, Li, R, Debusk, L, Lin, PC, Price, RR, Gore, JC Quantitative pharmacokinetic analysis of DCE-MRI data without an arterial input function: a reference region model Magn Reson Imaging 2005. 23:519-29

» Shin, I, Edl, J, Biswas, S, Lin, PC, Mernaugh, R, Arteaga, CL Proapoptotic activity of cell-permeable anti-Akt single-chain antibodies Cancer Res 2005. 65:2815-24

» Lin, Fa-Hsuan, Kwong, Kenneth K, Belliveau, John W, Wald, Lawrence L Parallel imaging reconstruction using automatic regularization Magn Reson Med 2004. 51:559-67

» DeBusk, Laura M, Hallahan, Dennis E, Lin, Pengnian Charles Akt is a major angiogenic mediator downstream of the Ang1/Tie2 signaling pathway Exp Cell Res 2004. 298:167-77

» Brissova, Marcela, Fowler, Michael, Wiebe, Peter, Shostak, Alena, Shiota, Masakazu, Radhika, Aramandla, Lin, P Charles, Gannon, Maureen, Powers, Alvin C Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets Diabetes 2004. 53:1318-25

» Peters, Kevin G, Kontos, Christopher D, Lin, P Charles, Wong, Adrianne L, Rao, Prema, Huang, Liwen, Dewhirst, Mark W, Sankar, Sabita Functional significance of Tie2 signaling in the adult vasculature Recent Prog Horm Res 2004. 59:51-71

» Price R, Green-Jarvis B, Williams M, Lee H and Lin, P. C Tumor Microvascularity Assessment with Contrast Enhanced MRI Medical Physics 2004. 31:1773

» Nishishita, Toshishita, Lin, Pengnian Charles Angiopoietin 1, PDGF-B, and TGF-beta gene regulation in endothelial cell and smooth muscle cell interaction J Cell Biochem 2004. 91:584-93

» Roberts, Richard L, Lin, Pengnian Charles Structural and functional optical imaging of angiogenesis in animal models Methods Enzymol 2004. 386:105-22

» Chen, Jian-Xiong, Chen, Ying, DeBusk, Laura, Lin, Wenyu, Lin, Pengnain Charles Dual functional roles of Tie-2/angiopoietin in TNF-alpha-mediated angiogenesis Am J Physiol Heart Circ Physiol 2004. 287:H187-95

» Yang, Li, DeBusk, Laura M, Fukuda, Koari, Fingleton, Barbara, Green-Jarvis, Brenda, Shyr, Yu, Matrisian, Lynn M, Carbone, David P, Lin, P Charles Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis Cancer Cell 2004. 6:409-21

» Lin, Pengnain Charles Optical imaging and tumor angiogenesis J Cell Biochem 2003. 90:484-91

» DeBusk, Laura M, Chen, Ying, Nishishita, Toshihide, Chen, Jin, Thomas, James W, Lin, Pengnain Charles Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis Arthritis Rheum 2003. 48:2461-71

» Brantley, Dana M, Cheng, Nikki, Thompson, Erin J, Lin, Qing, Brekken, Rolf A, Thorpe, Philip E, Muraoka, Rebecca S, Cerretti, Douglas Pat, Pozzi, Ambra, Jackson, Dowdy, Lin, Charles, Chen, Jin Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo Oncogene 2002. 21:7011-26

» Tomanek, R J, Zheng, W, Peters, K G, Lin, P, Holifield, J S, Suvarna, P R Multiple growth factors regulate coronary embryonic vasculogenesis Dev Dyn 2001. 221:265-73

» Geng, L, Donnelly, E, McMahon, G, Lin, P C, Sierra-Rivera, E, Oshinka, H, Hallahan, D E Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy Cancer Res 2001. 61:2413-9

» Li, C Y, Shan, S, Huang, Q, Braun, R D, Lanzen, J, Hu, K, Lin, P, Dewhirst, M W Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models J Natl Cancer Inst 2000. 92:143-7

» Hughes, G C, Annex, B H, Yin, B, Pippen, A M, Lin, P, Kypson, A P, Peters, K G, Lowe, J E, Landolfo, K P Transmyocardial laser revascularization limits in vivo adenoviral-mediated gene transfer in porcine myocardium Cardiovasc Res 1999. 44:81-90

» Huang, L, Sankar, S, Lin, C, Kontos, C D, Schroff, A D, Cha, E H, Feng, S M, Li, S F, Yu, Z, Van Etten, R L, Blanar, M A, Peters, K G HCPTPA, a protein tyrosine phosphatase that regulates vascular endothelial growth factor receptor-mediated signal transduction and biological activity J Biol Chem 1999. 274:38183-8

» Annex, B H, Torgan, C E, Lin, P, Taylor, D A, Thompson, M A, Peters, K G, Kraus, W E Induction and maintenance of increased VEGF protein by chronic motor nerve stimulation in skeletal muscle Am J Physiol 1998. 274:H860-7

» Lin, P, Sankar, S, Shan, S, Dewhirst, M W, Polverini, P J, Quinn, T Q, Peters, K G Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor Cell Growth Differ 1998. 9:49-58

» Lin, P, Buxton, J A, Acheson, A, Radziejewski, C, Maisonpierre, P C, Yancopoulos, G D, Channon, K M, Hale, L P, Dewhirst, M W, George, S E, Peters, K G Antiangiogenic gene therapy targeting the endothelium-specific receptor tyrosine kinase Tie2 Proc Natl Acad Sci U S A 1998. 95:8829-34

» Lin, P, Polverini, P, Dewhirst, M, Shan, S, Rao, P S, Peters, K Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth J Clin Invest 1997. 100:2072-8