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Novel Signaling Mechanisms for Endoglin During Angiogenesis

Pan, Chris C

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Pharmacy.
Endoglin is an endothelial-specific TGF-ß co-receptor that is essential for angiogenesis and vascular remodeling. It regulates a wide range of cellular and biological processes, including cell proliferation, migration and adhesion. Endoglin’s importance in endothelial biology is highlighted by the embryonic lethal phenotypes observed in endoglin knockout mice and by the presence of vascular diseases including the autosomal dominant disorder, HHT1. Aside from normal angiogenesis, endoglin has a critical role in tumor-associated angiogenesis and has become a therapeutic target for the treatment of many solid tumor types. Despite its therapeutic potential and established role in physiology and disease, the underlying mechanisms for endoglin’s actions are poorly defined. In Chapter I, we demonstrate that endoglin inhibits endothelial proliferation by suppressing ERK activation. In Chapter II, we establish endoglin’s evolutionary conserved tyrosine motif as a critical determinant of its stability and function. In Chapter III, we show that endoglin promotes angiogenesis by inducing endothelial autophagy. Lastly, in Chapter IV, we define a novel mechanism by which the endoglin-targeting antibody, TRC105, neutralizes endoglin function through direct coupling of MMP-14 and endoglin at the cell surface. Taken together, the work presented here provides a greater understanding of endoglin biology, defines several novel signaling mechanisms for endoglin during angiogenesis, and highlights endoglin’s therapeutic potential.
Nam Lee (Advisor)
Dale Hoyt (Committee Member)
Keli Hu (Committee Member)
167 p.

Recommended Citations

Citations

  • Pan, C. C. (2016). Novel Signaling Mechanisms for Endoglin During Angiogenesis [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1468451077

    APA Style (7th edition)

  • Pan, Chris. Novel Signaling Mechanisms for Endoglin During Angiogenesis . 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1468451077.

    MLA Style (8th edition)

  • Pan, Chris. "Novel Signaling Mechanisms for Endoglin During Angiogenesis ." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1468451077

    Chicago Manual of Style (17th edition)