Office: 843-792-5786
Lab: 843-792-6748
Fax: 843-792-1627
Email: chaol@musc.edu
BSB-535C

Research Interests

My laboratory's current research effort focuses on four areas. The first is to analyze the structure, organization and regulation of the genes involved in the kallikrein-kinin system. The primary function of kallikrein is to cleave low molecular weight kininogen to produce the vasoactive kinin peptide. We are analyzing the promoter of kallikrein genes by gel retardation assays and foot-printing analysis and probing the function of the kallikrein-kinin system by transgenic analysis and by homologous recombination. A number of transgenic mouse lines expressing the human tissue kallikrein gene have been generated for functional studies. Second, we are using genetically hypertensive animal models to explore the role of the kallikrein-kinin system in hypertension and to clone the defective kallikrein gene from the hypertensive animal to study the genetic defects at the molecular level. Hypertensive human populations and selected pedigrees are used to evaluate kallikrein-kinin genotypes as potential risk factors in essential hypertension and to use genotyping as a tool to identify individuals who may be predisposed to the risk factors for intervention and treatment. Third, we are developing gene delivery techniques as a tool for studying gene expression in vivo. We have successfully delivered various constructs into rat muscle, kidney, heart, lung, brain and vasculature for direct biochemical, molecular biological and physiological studies. Further development of the delivery technology could make it widely applicable for studying gene function, regulation and interaction at molecular, cellular and organismal levels. Four, we are exploring somatic gene therapy for cardiovascular and hypertensive diseases. A major objective is to improve the vector system for long-term expression in vivo. In addition, we are exploring the potential of using gene delivery to prevent tissue damage such as kidney damage caused by high salt diet and damage to the heart caused by ischemia and reperfusion.

Selected Publications

• Wang, C., Dobrzynski, E., Chao, J. and Chao, L. (2001) Adrenomedullin gene delivery attenuates renal damage and cardiac hypertrophy in Goldblatt hypertensive rats. Am. J. Physiol. Renal Physiol., 280(6): F964-F971.
• Chen, L.M., Skinner, M.L., Kauffman, S.W., Chao, J., Chao, L., Thaler, C.D., and Chai, K.X. (2001) Prostasin is a glycosylphosphatidylinositol-anchored active serine protease. J. Biol. Chem., 276(24): 21434-21442.
• Chao, J., Miao, R.Q., Chen, V., Chen, L.M. and Chao, L. (2001) Novel roles of kallistatin, a specific tissue kallikrein inhibitor, in vascular remodeling. Biol. Chem., 382(1): 15-21.
• Emmanueli, C., minasi, A., Zacheo, A., Chao, J., Chao, L., Salis, M.B., Straino, S., Tozzi, M.G., Smith, R., Gaspa, L., Bianchini, G., Stillo, F., Capogrossi, M.C., Madeddu, P. (2001) Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia. Circulation, 103(1): 125-132.
• Chen, V.C., Chao, L., Pimenta, D.C., Bledsoe, G., Juliano, L. and Chao, J. (2001) Identification of a major heparin-binding site in kallistatin. J. Biol. Chem., 276(2): 1276-1284.
• Emanueli, C., Zacheo, A., Minasi, A., Chao, J., Chao, L., Salis, M.B., Stacca, T., Straino, S., Capogrossi, M.C., Mededdu, P. (2000) Adenovirus-mediated human tissue kallikrein gene delivery induces angiogenesis in normoperfused skeletal muscle. Arterioscler. Thrmob. Vasc. Biol., 20(11): 2379-2385.
• Silva, J.A., Jr., Araujo, R.C., Baltatu, O., Oliveira, S.M., Tschope, C., Fink, E., Hoffman, S., Plehm, R., Chai, K.X., Chao, L., Chao, J., Ganten, D., Pesquero, J.B., and Bader, M. (2000) Reduced cardiac hypertrophy and altered blood pressure control in transgenic rats with the human tissue kallikrein gene. FASEB J., 14(13): 1858-1860.
• Chen, V.C., Chao, L. and Chao, J. (2000) Roles of the P1, P2, and P3 residues in determining inhibitory specificity of kallistatin toward human tissue kallikrein. J. Biol. Chem., 275(49): 38457-38466.
• Chen, V.C., Chao, L., and Chao, J. (2000) A positively charged loop on the surface of kallistatin functions to enhance tissue kallikrein inhibition by acting as a secondary binding site for kallikrein. J. Biol. Chem., 275(51): 40371-40377.
• Agata, J., Miao, R.Q., Yayama, K., Chao, L., and Chao, J. (2000) Bradykinin B(1) receptor mediates inhibition of neointima formation in rat artery after balloon angioplasty. Hypertension, 36(3): 364-370.
• Zhang, J.J., Yoshida, H., Chao, L. and Chao, J. (2000) Human adrenomedullin gene delivery protects against cardiac hypertrophy, fibrosis, and renal damage in hypertensive dahl salt-sensitive rats. Human Gene Therapy, 11(13): 1817-1827.
• Wolf, W.C., Yoshida, H., Agata, J., Chao, L. and Chao, J. (2000) Human tissue kallikrein gene delivery attenuates hypertension, renal injury, and cardiac remodeling in chronic renal failure. Kidney Int., 58(2): 730-739.
• Emanueli, C., Bonaria Salis, M., Figueroa, C., Chao, J., Chao, L., Gaspa, L., Capogrossi, M.C., Madeddu, P. (2000) Participation of kinins in the captopril-induced inhibition of intimal hyperplasia caused by interruption of carotid blood flow in the mouse. Br. J. Pharmacol., 30(5): 1076-1082.
• Chen, V.C., Chao, L. and Chao, J. (2000) Reactive-site specificity of human kallistatin toward tissue kallikrein probed by site-directed mutagenesis. Biochim. Biophys. Acta., 1479(1-2): 237-246.
• Emanueli, C., Salis, M.B., Chao, J., Chao, L., Agata, J., Lin, K-F., Munao, A., Straino, S., Minasi, A., Capogrossi, M.C., Madeddu, P. (2000) Adenovirus-mediated human tissue kallikrein gene delivery inhibits neointima formation induced by interruption of blood flow in mice. Arterioscler. Thromb. Vasc. Biol., 20(6): 1459-1466.
• Wang, D., Yoshida, H., Song, Q., Chao, L., and Chao, J. (2000) Enhanced renal function in bradykinin B(2) receptor transgenic mice. Am. J. Physiol. Renal Physiol., 278(3): F484-F491.
• Miao, R.Q., Murakami, H., Song, Q., Chao, L. and Chao, J. (2000) Kallistatin stimulates vascular smooth muscle cell proliferation and migration in vitro andneointima formation in balloon-injured rat artery. Circ. Res., 86(4): 418-424.
• Yoshida, H., Zhang, J.J., Chao, L. and Chao, J. (2000) Kallikrein gene delivery attenuates myocardial infarction and apoptosis after myocardial ischemia and reperfusion. Hypertension, 35(Pt. 1): 25-31.
• Dobrzynski, E., Wang, C., Chao, J., and Chao, L. (2000) Adrenomedullin gene delivery attenuates hypertension, cardiac remodeling, and renal injury in deoxycorticosterone acetate-salt hypertensive rats. Hypertension, 36(6): 995-1001.
• Murakami, H., Miao, R.Q., Chao, L. and Chao, J. (1999) Adenovirus-mediated kallikrein gene transfer inhibits formation via increased production of nitric oxide in rat artery. Immunopharmacology, 44(1-2): 137-143.
• Dobrzynski, E., Yoshida, H., Chao, J. and Chao, L. (1999) Adenovirus-mediated kallikrein gene delivery attenuates hypertension and protects against renal injury in deoxycorticosterone-salt rats. Immunopharmacology, 44(102): 57-65.
• Madeddu, P., Emanueli, C., Gaspa, L., Salid, B., Milia, A.F., Chao, L. and Chao, J. (1999) Role of the bradykinin B2 receptor in he maturation of blood pressure phenotype: lesson from transgenic and knockout mice. Immunopharmacology, 44(1-2): 9-13.
• Zhang, J.J., Wang, C., Lin, K-F., Chao, L. and Chao, J. (1999) Human tissue kallikrein attenuates hypertension and secretes into circulation and urine after intramuscular gene delivery in hypertensive rats. Clin. Exp. Hypertens., 21(7): 1145-1160.
• Hatcher, H.C., Wright, N.M., Chao, J., Chao, L. and Ma, J.X. (1999) Kallikrein-binding protein is induced by growth hormone in the dwarf rat. FASEB J., 13(13): 1839-1844.
• Wolf, W.C., Harley, R.A., Sluce, D., Chao, L. and Chao, J. (1999) Localization and expression of tissue kallikrein and kallistatin in human blood vessels. J. Histochem. Cytochem., 47: 221-228.
• Murakami, H., Yayama, K., Miao, R.Q., Wang, C., Chao, L. and Chao, J. 1999. Kallikrein gene transfer inhibits vascular smooth muscle cell growth and neointima formation in the rat artery after balloon angioplasty. Hypertension, 34: 164-170.
• Zhang, J.J., Chao, L. and Chao, J. (1999) Adenovirus-Mediated Kallikrein Delivery Reduces Aortic Thickening and Stroke-Induced Death Rate in Dahl Salt-Sensitive Rats. Stroke 30: 1925-1932.