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Department of Medicine

Department of Medicine

  Division of Pulmonary, Allergy and Critical Care Medicine



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photo Yutong Zhao, MD, PhD

Associate Professor of Medicine

Associate Professor of Cell Biology

Co-Director of Acute Lung Injury Center of Excellence

Email: zhaoy3@upmc.edu

Phone: 412-648-9488

Contact
Office: 3459 Fifth Avenue
628 NW MUH
Pittsburgh, PA 15213
 
Phone: 412-648-9488
Fax: 412-383-7113
E-mail: zhaoy3@upmc.edu
Administrative Assistant:
Roe Catley
Email: catlrx@upmc.edu
Phone: 412-624-8669
Fax: 412-383-7113
Education and Training
Education
MD, Dalian Medical University, Dalian, China, 1994
PhD, Biochemistry, Gifu University School of Medicine, Gifu, Japan, 2000
Pulmonary Research Fellow, Johns Hopkins University School of Medicine, Baltimore, MD, 2004
Research Interest
The primary goal of my laboratory research is to investigate the role of bio-active phospholipid receptors in the pathogenesis of sepsis and lung inflammatory diseases. We have discovered that lysophosphatdic acid (LPA) and its receptors play a critical role in regulating cytokine release and cytokine receptor expression, and the pro-inflammatory effects are mediated by GPCR and cross-talk with LPS co-receptor, CD14. Our current project is to reveal molecular regulation of LPA receptors by ubiquitination and de-ubiquitination.

A second research field in my laboratory is to understand the role of de-ubiquitination enzymes in the regulation of of the interleukin-1 receptor/Toll-like receptors (TLRs). We have been investigating on the IL-33 receptor ubiquitination, phosphorylation, and internalization. We uncovered a new ubiquitin E3 ligase regulates IL-33 receptor stability. Recently, we showed that phosphorylation of IL-33 receptor by GSK3ß promotes IL-33 receptor internalization. Currently, we are focusing on molecular regulation of IL-1R8 stability in lung injury and sepsis.

We are also interested in revealing the role of de-ubiquitination enzymes in TGFß signaling, tumorigenesis, and innate and adaptive immunity. Our research works show that TGFRII and Smad2/3 stability are tightly controlled by USP11 and UCHL5. We are focusing on the molecular regulation of key transcriptional factors stability by novel de-ubiquitination enzymes.
Educational Interest
We are training pulmonary fellows, residences, medical students, undergraduate students, postdoc fellows the pulmonary, cellular, and molecular biology.
Publications
For my complete bibliography, Click Here.
Selected Publications:
He, D., Su, Y., Usatyuk, P. V., Spannhake, E. W., Kogut, P., Solway, J., Natarajan, V., Zhao, Y. Lysophosphatidic acid enhances pulmonary epithelial barrier integrity and protects endotoxin-induced epithelial barrier disruption and lung injury. Journal of Biological Chemistry. 2009; 284(36): 24123-32.
He, D., Natarajan, V., Stern,R., Gorshkova, I. A., Solway, J., Spannhake, E. W., Zhao, Y. Lysophosphatidic acid-induced transactivation of epidermal growth factor receptor regulates cyclo-oxygenase-2 expression and prostaglandin E(2) release via C/EBPbeta in human bronchial epithelial cells. Biochemical Journal. 2008; 412(1): 153-62.
Zhao, J., Wei, J., Mialki, R. K., Mallampalli, D. F., Chen, B. B., Coon, T., Zou, C., Mallampalli, R. K., Zhao, Y. F-box protein FBXL19-meidated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation. Nature Immunology. 2012; 13(7): 651-8.
Zhao, J., Mialki, R. K., Wei, J., Coon T. A., Zou, C., Chen, B. B., Mallampalli, R. K., Zhao, Y. SCF E3 ligase F-box protein complex SCF(FBXL19) regulates cell migration by mediating Rac1 ubiquitination and degradation. FASEB Journal. 2013; 27(7): 2611-9.
Mialki, K. R., Zhao, J., Wei, J., Mallampalli, D. F., Zhao, Y. Over-expression of USP14 protease reduces I-?B levels and increases cytokine release in lung epithelial cells. Journal of Biological Chemistry. 2013; 288(22): 15437-41.
Zhao, J, Wei, J, Bowser, R. K., Traister, S. R., Fan, M-H., Zhao, Y. Focal adhesion kinase-mediated activation of glycogen synthase kinase 3ß regulates IL-33-induced ST2L internalization and IL-33 signaling. Journal of Immunology. 2015; 194(2): 795-802.
Zhao, J., Wei, J., Dong, S., Bowser, R. K., Zhang, L., Jacko, A. M., Zhao, Y. Destabilization of lysophosphatidic acid receptor 1 reduces cytokine release and protects against lung injury. Ebiomedicine. 2016; in press.
Sponsored Research/Activities
Title: Regulation of the IL-33 Receptor, ST2L, by Protein Stability in Septic Injury
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL112791
Start Year: 2013
End Year: 2017
Title: Lysophosphatidic Acid in Airway Barrier Function and Remodeling
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL091916
Start Year: 2010
End Year: 2015
Title: HIPPO Signaling in Pulmonary Arterial Hypertension
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL130261
Start Year: 2016
End Year: 2020
Title: Regulation of Histone Acetyltransferase Stability in Sepsis
Role: Co-Investigator
Funding Agency: National Institute of General Medical Science
Grant Number: R01 GM115389
Start Year: 2015
End Year: 2020
Title: Cardiolipin as a Novel Mediator of Acute Lung Injury - Project 1
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: P01 HL114453
Start Year: 2014
End Year: 2018
Title: Hemostasis and Vascular Biology Research Institute - Zhao
Role: Co-Investigator
Funding Agency: Institute for Transfusion Medicine
Start Year: 2013
End Year: 2028
Title: Septic Lung Injury and Surfactant
Role: Faculty Collaborator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL098174
Start Year: 2010
End Year: 2017
Notable Achievements
Member, American Thoracic Society, 2006-current
Member, American Federation for Medical Research Society, 2006-current
Member, American Physiology Society, 2013-current
Member, American Society for Clinical Investigation, 2014-current
Cardiovascular Investigator Award from CSCTR, 2008
Henry Christian Award from AFMR, 2008
Outstanding Young Investigator Award from CSCTR, 2012
Outstanding Investigator Award from AFMR, 2014
Reviewer, NIH NCI SBIR study section, 2010
Reviewer, American Heart Association lung study section, 2012-current