Department of biochemistry and Molecular biology
Julie Chao, PhD
Biochemistry and Molecular Biology
1971-1974 Postdoctoral Research, University of Connecticut
1970 Ph.D., Iowa State University
1967 M.S., Utah State University
We have been studying the role and molecular basis of tissue kallikrein, kinin B1 and B2 receptors, related vasodilating peptides/proteins, prostasin and kallistatin in hypertension, cardiovascular and renal injury, and ischemic stroke for 40 years. Our work has involved a wide range of activities, including protein purification, molecular cloning, regulation of enzyme activity and gene expression, signaling pathways, and therapeutic gene/protein delivery in various animal models. We have discovered, purified and cloned two new human proteins: prostasin and kallistatin. Prostasin, a serine proteinase, plays crucial roles in sodium balance regulation, bladder inflammation and tumor invasion. Kallistatin, a specific tissue kallikrein inhibitor, exerts pleiotropic functions in vasodilation, and modulating angiogenesis, inflammation, apoptosis, fibrosis, and tumor growth and metastasis. We are currently investigating the role and mechanisms of kallistatin in vascular repair. Our hypothesis is that kallistatin protects against vascular injury by: 1) inhibiting oxidative stress and inflammation, 2) stimulating the mobilization and functional activity of endothelial progenitor cells, and 3) preventing endothelial senescence. Our objective is to identify new avenues in rejuvenating endothelial function in cardiovascular and related diseases.
Guo YM, Li PF, Gao L, Zhang JM, Yang ZR, Bledsoe G, Chang E, Chao L, Chao J. (2017) Kallistatin reduces vascular senescence and aging by regulating microRNA-34a-SIRT1 pathway. Aging Cell 16:837-846.
Chao J, Li PF, Chao L. (2017) Kallistatin suppresses cancer development via multi-factorial actions. Critical Reviews in Oncology/Hematology 113:71-78.
Chao J, Bledsoe G, Chao L. (2016) Kallistatin: A protective agent for vascular and organ injury. Hypertension 68:533-541.
Li P, Guo Y, Bledsoe G, Yang ZR, Chao L, Chao J. (2016) Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis. Experimental Cell Research 340(2):305-314.
Li P, Guo Y, Bledsoe G, Yang ZR, Fan H, Chao L, Chao J. (2015) Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis. Critical Care 19(1):200.
Gou Y, Li P, Bledsoe G, Yang ZR, Chao L, Chao J. (2015) Kallistatin inhibits TGF-β-induced endothelial-mesenchymal transition by differential regulation of microRNA-21 and eNOS expression. Experimental Cell Research 337:103-110.
Chao J, Bledsoe G, Chao L. (2015) Kallistatin: a novel biomarker for organ injury and cancer. Invited review article for Austin Biomarkers & Diagnosis.
Lin, WC, Chen CW, Chao L, Chao J, Lin YS, Lin CF. (2015) Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis. Scientific Reports 5:12463.
Li PF, Bledsoe G, Yang ZR, Fan HF, Chao L, Chao J. (2014) Human kallistatin administration reduces organ injury and improves survival in a mouse model of polymicrobial sepsis. Immunology 142(2):216-226.
Chao J, Bledsoe G, Chao L. (2014) Tissue kallikrein-kinin therapy in hypertension and organ damage. Prog Drug Res 69:37-57.
Gao L, Li PF, Hagiwara M, Shen B, Bledsoe G, Chang E, Chao L, Chao J. (2014) Novel role of kallistatin in vascular repair by promoting mobility, viability, and function of endothelial progenitor cells. Journal of American Heart Association 3(5):e001194.
Chao J, Bledsoe G, Chao L. (2014) Kallikrein-kinin in stem cell therapy. Special issue of World Journal Stem Cells 6(4):448-457.
Gao L, Hang Y, Bledsoe G, Shen B, Chao L, Chao J. (2013) Tissue kallikrein-modified mesenchymal stem cells protect against ischemic cardiac injury after myocardial infarction. Circulation Journal 77:2134-2144.
Zhang J, Yang ZR, Li PF, Bledsoe G, Chao L, Chao, J. (2013) Kallistatin blocks Wnt/β-catenin signaling and cancer cell motility by binding to LRP6. Molecular and Cellular Biochemistry 379:295-301.
Lu SL, Tsai CY, Luo YH, Kuo CF, Lin WC, Chang YT, Wu JJ, Chuang WJ, Liu CC, Chao L, Chao J, Lin YS. (2013) Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group A Streptococcal infection. Antimicrobial Agents and Chemotherapy 57:5366-5372.
Yao YY, Sheng CF, Li Y, Cong F, Ma G., Liu N, Chao J, Chao L. (2013) Tissue kallikrein-modified human endothelial progenitor cell implantation improves cardiac function via enhanced activation of Akt and increased angiogenesis. Laboratory Investigation 93:577-591.
Guo DH, Parikh S, Chao J, Pollock N, Wang X, Snieder H, Navis G, Wilson J, Bhagatwala J, Zhu H, Dong YB. (2013) Urinary prostasin excretion is associated with adiposity in non-hypertensive African American adolescents. Pediatric Research 74:206-210.
Yao YY, Li Y, Sheng Z, Yan F, Ma G, Liu N, Chao J, Chao L. (2012) Tissue kallikrein promotes cardiac neovascularization by enhancing endothelial progenitor cell migration and functional capacity. Human Gene Therapy 23(8):859-870. PMID: 22435954
Liu YY, Bledsoe G, Hagiwara M, Shen B, Chao L, Chao J. (2012) Depletion of endogenous kallistatin exacerbates renal and cardiovascular oxidative stress, inflammation and organ remodeling. Am J Physiology 303(8):F1230-1238.