Department of biochemistry and Molecular biology
Julie Chao
Julie Chao, Ph.D.
Professor
Biochemistry and Molecular Biology
1971-1974 Postdoctoral Research, University of Connecticut
Education
1970 Ph.D., Iowa State University
1967 M.S., Utah State University
Contact Info
Email: chaoj@musc.edu
Office: 843-792-9927
Lab: 843-792-6748
Fax: 843-792-8568
BSB-518A
Research Interests
Role of Tissue Kallikrein in Cardiovascular and Renal Diseases
Our studies have focused on the role and mechanisms of the tissue kallikrein-kinin system (KKS) in blood pressure regulation, cardiovascular, cerebrovascular, and renal function. The KKS can be blocked by specific kinin receptor antagonists, and kallikrein’s activity is inhibited by the endogenous protein kallistatin. Tissue kallikrein, through kinin formation and kinin receptor activation, exerts a wide spectrum of biological actions. Using gene delivery, protein infusion, and mesenchymal stem cell approaches, we have demonstrated that tissue kallikrein through kinin B2 receptor signaling reduces cardiac and renal damage, restenosis and ischemic stroke, and promotes angiogenesis and skin wound healing, independent of blood pressure reduction. Protection by tissue kallikrein in organ damage is attributed to its pleiotropic effects by inhibiting apoptosis, inflammation, hypertrophy and fibrosis through multiple signaling pathways. Our recent studies indicated that tissue kallikrein can also directly activate the kinin B2 receptor or proteinase-activated receptor independent of kinin generation. The information obtained from these studies will be useful for potential application of tissue kallikrein in the prevention and treatment of heart failure, renal disease and stroke in humans.
Role of Kallistatin in Inflammation-Induced Angiogenesis and Tumor Progression
Kallistatin was discovered and identified as a tissue Kallikrein-binding protein in our laboratory. We have demonstrated that kallistatin is a regulator of vascular homeostasis capable of controlling a broad range of biological effects independent of its interaction with tissue kallikrein. Kallistatin through its heparin-binding site competes with the binding of tumor necrosis factor-α and vascular endothelial growth factor to endothelial cells, thus preventing inflammation, vascular permeability and angiogenesis. We have shown that kallistatin inhibits vascular injury, inflammation, angiogenesis and tumor growth in several animal models. We have also demonstrated that kallistatin levels are reduced in hypertensive and normotensive animals with oxidative organ damage. However, kallistatin administration by gene delivery into these animal models reduces hypertension, vascular and organ injuries associated with suppression of apoptosis, inflammation, hypertrophy and fibrosis. Moreover, circulating kallistatin levels are markedly reduced in patients with colon, prostate, and liver cancer. We are currently investigating the potential role of kallistatin in protection against tumor progression by inhibiting angiogenesis and cancer cell invasiveness. These studies could reveal important information regarding the role and mechanism of kallistatin in inflammation-associated angiogenesis, cancer progression and prognosis.
Recent Publications
1. Zhu H, Chao J, Kotak I, Guo D, Rarikh S, Bhagatwala J, Patel SY, Houk C, Chao L, Dong Y. 2013. Plasma kallistatin is associated with adiposity and cardiometabolic risk in apparently healthy African American adolescents. Metabolism, in press.
2. 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, in press.
3. 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, in press.
4. Zhou J, Zhang ZM, Chao J. 2012. Porphyromonas gingivalis promotes monocyte migration by activating MMP-9. J. Peridontal Research, 47(2):236-242.
5. Patel AB, Chao J, Palmer LG. 2012. Tissue kallikrein activation of the epithelial Na channel. Am. J. Physiology 303(4):F540-550. PMID: 22622459
6. 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
7. 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.