We have been working on the effects of snake venom components on blood coagulation, platelet aggregation, cell-matrix interaction, angiogenesis, and tumor metastasis since 1972. Snake venoms contain many unique components that affect cell-matrix interactions. Disintegrins represent a class of low molecular weight, Arg (or Lys )-Gly-Asp (R/KGD ) containing, cysteine-rich polypeptides which bind specifically to integrin aIIbb3, avb3, and a5b1 expressed on platelets, endothelial cells, fibroblasts and other cells. Integrins are transmembrane, heterodimeric complex, and mediate platelet aggregation, cell adhesion, migration, and proliferation, playing important roles in thrombosis, wound healing, inflammatory reaction, tissue remodelling, angiogenesis and tumor metastasis. Disintegrins have been successfully developed as lead compounds in field of the antithrombosis, and anti-angiogenesis.

Our laboratory currently focuses our studies on the effects of disintegrins on adhesion, migration and proliferation of endothelial cells and smooth muscle cells, and tumor- or growth factor-induced angiogenesis. Both in vivo and in vitro models are used to assess these topics at a molecular level. In addition, snake venom metalloproteinases (MPs), platelet glycoprotein (GP) Ib binding proteins, a2b1 and GPVI agonists are also explored in field of thrombosis and angiogenesis. The structure-function relationships of these proteins are being investigated by means of genetic cloning, protein expression and genetic manipulation, aiming to further explore the potential clinical application of the new classes of anti-thrombotic, anti-angiogenic and anti-metastatic agents.

Publications:

1] Snake Venom Disintegrin Inhibits the Activation of Toll-Like Receptors and Alleviates Sepsis through Integrin alphaVbeta3 Blockade.  Sci Reports. 6 : 23387, 2016.  [Abstract]

2] A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models. Thrombosis and Haemostasis. Epub ahead of print: May 12;116(2), 2016.  [Abstract]

3] Antiangiogenic mechanism of PJ-8, a novel inhibitor of vascular endothelial growth factor receptor signaling. Carcinogenesis. 33(5):1022-30. 2012. [Abstract]

4] NP-313, 2-Acetylamino-3-chloro-1,4-naphthoquinone, a novel antithrombotic agent with dual inhibition on thromboxane A2 synthesis and calcium entry. Br J Pharmacol. 162(8):1871-1883, 2011. [Abstract]

5] A novel mechanism of cytokine release in phagocytes induced by aggretin, a snake venom C-type lectin protein, through CLEC-2 ligation. J. Thromb. Haemost, 8(11):2563-2570. 2010.  [Abstract]

We are carrying out some projects regarding the effects and molecular characterization of snake venom components, including disintegrins, metalloproteinases, GPIb binding proteins, and integrin a2b1 agonist, in field of thrombosis, angiogenesis and tumor metastasis. The structure-function relationships are explored by means of genetic cloning, protein expression, and genetic manipulation coupled with biological assays.

1] HPLC, FPLC for protein purification

2] PCR

3] Lumi-Aggregometer for measurement of ATP release and platelet aggregation