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Department of biochemistry and Molecular biology

Julie Chao, PhD

ProfessorJulie Chao, PhD
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, as well as 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 and a 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, while kallistatin depletion by neutralizing antibody injection has the opposite effects. We have shown that circulating kallistatin levels are markedly reduced in patients with liver disease, septic syndrome, severe pneumonia as well as colon, prostate, and liver cancer. Moreover, diminished kallistatin levels are associated with adiposity in healthy human population cohorts. We are currently investigating the role of kallistatin in vascular and organ damage by promoting endothelial progenitor cell viability, migration, and vasculogenic activity in animal models and cultured cells. These studieshttp://www.google.com/firefox?client=firefox-a&rls=org.mozilla:en-US:official could reveal important information regarding the role and mechanism of kallistatin in cardiovascular and renal diseases.

Recent Publications

1. 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, in press.

2. 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.

3. 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.

4. 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.

5. 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 Clinical and Experimental 62:642-646.

6. 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.

7. 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.

8. Patel AB, Chao J, Palmer LG. 2012. Tissue kallikrein activation of the epithelial Na channel. Am. J. Physiology 303(4):F540-550. PMID: 22622459

9. 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

10. 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.

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