BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Youhua Liu
eRA COMMONS USER NAME
Professor of Pathology
YOUHUA_LIU
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Anhui University, Anhui, China
China Medical University, Shenyang, China
Peking Union Medical College, Beijing, China
DEGREE
(if applicable)
YEAR(s)
B.S.
M. S.
Ph.D
1982
1985
1988
FIELD OF STUDY
Biochemistry
Cell Biology
Cell Biology
A. Positions and Honors:
Academic Appointment:
1989-1992: Fogarty Visiting Fellow, National Institute of Environmental Health Sciences, National
Institutes of Health
1992-1994: Postdoctoral Research Associate, Department of Pathology, University of Pittsburgh
School of Medicine
1994-1999: Assistant Professor of Medicine, Department of Medicine, Rhode Island Hospital, Brown
University School of Medicine
1999-2006: Associate Professor of Pathology, Department of Pathology, University of Pittsburgh
School of Medicine
2006-Date:
Professor of Pathology, Department of Pathology, University of Pittsburgh School of Medicine
Awards and Professional Activities:
Independent Scientist Award, NIDDK/NIH, 1999-2004; Ad hoc reviewer, NIH Fogarty Center Special
Program, 1998; Ad hoc member, NIH General Medicine B Study Section, 1999; Member, NIH/NIEHS
Special Emphasis Panel, 2000; International peer reviewer: Science Foundation Ireland, 2001; Expert
reviewer, Research Grants Council of Hong Kong, 2004; Ad hoc member, NIH Pathobiology of Kidney
Disease Study Section, 2004; Member, NIH Renal cell and Molecular Biology Special Emphasis Panel,
2004; Member, Editorial Board of Journal of the American Society of Nephrology; Organizer and Co-chair,
Symposium on “Epithelial-Mesenchymal Transition and Oncogenesis”, EB 2006.
B. Relevant publications (Selected from a total of 80):
1. Yang J, Shultz RW, Mars WM, Wegner RE, Li Y, Dai C, Nejak K, and Liu Y. 2002. Disruption of
tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive
nephropathy. J. Clin. Invest. 110: 1525-1538.
2. Yang J, and Liu Y. 2002. Blockage of tubular epithelial to myofibroblast transition by hepatocyte
growth factor prevents renal interstitial fibrosis. J. Am. Soc. Nephrol. 13: 96-107.
3. Dai C, Yang J, and Liu Y. 2002. Single injection of naked plasmid encoding hepatocyte growth factor
prevents cell death and ameliorates acute renal failure in mice. J. Am. Soc. Nephrol. 13: 411-422.
4. Yang J, Dai C, and Liu Y. 2002. Hepatocyte growth factor gene therapy and angiotensin II blockade
synergistically attenuate renal interstitial fibrosis in mice. J. Am. Soc. Nephrol. 13: 2464-2477.
5. Liu Y. 2002. Hepatocyte growth factor and the kidney. Curr. Opin. Nephrol. Hypertens. 11: 23-30.
6. Radaeva S, Jaruga B, Hong F, Kim WH, Fan S, Cai H, Strom S, Liu Y, El-Assal O, and Gao B. 2002.
Interferon-α activates multiple STAT signals and down-regulates c-Met in primary human hepatocytes.
Gastroenterology 122: 1020-1034.
7. Zhang X, Li Y, Dai C, Yang J, Mundel P, and Liu Y. 2003. Sp1 and Sp3 transcription factors
synergistically regulate HGF receptor gene expression in kidney. Am. J. Physiol. Renal Physiol.
284: F82-F94.
8. Yang J, and Liu Y. 2003. Delayed administration of hepatocyte growth factor reduces renal fibrosis in
obstructive nephropathy. Am. J. Physiol. Renal Physiol. 284: F349-F357.
9. Zhang X, and Liu Y. 2003. Suppression of HGF receptor gene expression by oxidative stress is
mediated through the interplay between Sp1 and Egr-1. Am. J. Physiol Renal Physiol. 284: F1216F1225.
10. Dai C, Yang J, and Liu Y. 2003. Transforming growth factor-β1 potentiates renal tubular epithelial cell
death by a mechanism independent of Smad signaling. J. Biol. Chem. 278: 12537-12545.
11. Dai C, Li Y, Yang J, and Liu Y. 2003. Hepatocyte growth factor preserves beta cell mass and
mitigates hyperglycermia in streptozotocin-induced diabetic mice. J. Biol. Chem. 278: 27080- 27087.
12. Yang J, Dai C, and Liu Y. 2003. Hepatocyte growth factor suppresses renal interstitial myofibroblast
activation and intercepts Smad signal transduction. Am. J. Pathol. 163: 621-632.
13. Li Y, Yang J, Dai C, Wu C, and Liu Y. 2003. Role for integrin-linked kinase in mediating tubular
epithelial to mesenchymal transition and renal interstitial fibrogenesis. J. Clin. Invest. 112: 503-516.
14. Zhang G, Kim H, Cai X, Lopez-Guisa JM, Alpers CE, Liu Y, Carmeliet P, and Eddy AA. 2003.
Urokinase receptor deficiency accelerates renal fibrosis in obstructive nephropathy. J. Am. Soc.
Nephrol. 14: 1254-1271.
15. Yang J, Zhang X, Li Y, and Liu Y. 2003. Down-regulation of Smad transcriptional corepressors SnoN
and Ski in the fibrotic kidney: an amplification mechanism for TGF-β1 signaling. J. Am. Soc. Nephrol.
14: 3167-3177.
16. Liang H, O’Reilly S, Liu Y, Abounader R, Laterra J, Maher VM, McCormick JJ. 2004. Sp1 regulates
expression of MET, and ribozyme-induced down-regulation of MET in fibrosarcoma-derived human
cells reduces or eliminates their tumorigenicity. Int. J. Oncol. 24: 1057-1067.
17. Liu Y. 2004. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance,
molecular mechanism and therapeutic intervention. J. Am. Soc. Nephrol. 15: 1-12.
18. Dai C, and Liu Y. 2004. Hepatocyte growth factor antagonizes the profibrotic action of TGF-β1 in
mesangial cells by stabilizing Smad transcriptional corepressor TGIF. J. Am. Soc. Nephrol. 15: 14021412.
19. Dai C, Yang J, Bastacky S, Xia J, Li Y, and Liu Y. 2004. Intravenous administration of hepatocyte
growth factor gene ameliorates diabetic nephropathy in mice. J. Am. Soc. Nephrol. 15: 2637-2647.
20. Liu Y. 2004. Hepatocyte growth factor in kidney fibrosis: therapeutic potential and molecular
mechanism. Am. J. Physiol. Renal Physiol. 287: F7-F16.
21. Zhang X, Yang J, Li Y, and Liu Y. 2005. Both Sp1 and Smad participate in mediating TGF-β1-induced
HGF receptor expression in renal epithelial cells. Am. J. Physiol. Renal Physiol. 288: F16-F26.
22. Yang J, Dai C, and Liu Y. 2005. A novel mechanism by which hepatocyte growth factor blocks tubular
epithelial to mesenchymal transition. J. Am. Soc. Nephrol. 16: 68-78.
23. Volonte D, Liu Y, and Galbiati F. 2005. The modulation of caveolin-1 expression controls satellite cell
activation during muscle repair. FASEB J. 19: 237-239.
24. Dai C, Huh CG, Thorgeirsson SS, and Liu Y. 2005. Beta-cell-specific ablation of the hepatocyte growth
factor receptor results in reduced islet size, impaired insulin secretion and glucose intolerance. Am. J.
Pathol. 167: 429-436.
25. Li Y, Spataro BC, Yang J, Dai C, and Liu Y. 2005. 1,25-Dihydroxyvitamin D3 inhibits renal interstitial
myofibroblast activation by inducing hepatocyte growth factor expression. Kidney Int. 68: 1500-1510.
26. Wen X, Li Y, Hu K, Dai C, and Liu Y. 2005. Hepatocyte growth factor receptor signaling mediates the
anti-fibrotic action of 9-cis-retinoic acid in glomerular mesangial cells. Am. J. Pathol. 167: 947-957.
27. Li Y, Wen X, Spataro BC, Hu K, Dai C, and Liu Y. 2006. Hepatocyte growth factor is a downstream
effector that mediates the anti-fibrotic action of peroxisome proliferator-activated receptor-γ agonists. J.
Am. Soc. Nephrol. 17: 54-65.
28 Liu Y. 2006. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int. 69: 213217.
29 Hu K, Yang J, Tanaka S, Gonias SL, Mars WM, and Liu Y. 2006. Tissue-type plasminogen activator
acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9
gene expression. J. Biol. Chem. 281: 2120-2127.
30. Giannopoulou M, Iszkula SC, Dai C, Tan X, Yang J, Michalopoulos GK, and Liu Y. 2006. Distinctive
role of Stat3 and Erk-1/2 activation in mediating interferon-γ inhibition of TGF-β1 action. Am. J. Physiol.
Renal Physiol. 290: F1234-F1240.
31. Xia J, Dai C, Michalopoulos GK, and Liu Y. 2006. Hepatocyte growth factor attenuates liver fibrosis
induced by bile duct ligation. Am. J. Pathol. 168: 1500-1512.
32. Liu Y. 2006. Rapamycin and chronic kidney disease: beyond the inhibition of inflammation. Kidney
Int. 69: 1925-1927.
33. Dai C, Stolz DB, Bastacky SI, St-Arnaud R, Wu C, Dedhar S, and Liu Y. 2006. Essential role of
integrin-linked kinase in podocyte biology: bridging the integrin and slit diaphragm signaling. J. Am.
Soc. Nephrol. 17: 2164-2175.
34. Liu Y, and Yang J. 2006. Hepatocyte growth factor: new arsenal in the fights against renal fibrosis?
Kidney Int. 70: 238-240.
35. Tan R, Zhang J, Tan X, Zhang X, Yang J, and Liu Y. 2006. Downregulation of SnoN expression in
obstructive nephropathy is mediated by an enhanced ubiquitin-dependent degradation. J. Am. Soc.
Nephrol. 17: 2781-2791.
36. Tan X, Li Y, and Liu Y. 2006. Paricalcitol attenuates renal interstitial fibrosis in obstructive
nephropathy. J. Am. Soc. Nephrol. 17: 3382-3393.
37. Apte U, Zeng G, Muller P, Tan X, Micsenyi A, Cipley B, Dai C, Liu Y, Kaestner KH, and Monga SPS.
2006. Activation of Wnt/β-catenin pathway during hepatocyte growth factor-induced hepatomegaly.
Hepatology. 44: 992-1002.
38. Tian J, Liu Y, Williams LA, and de Zeeuw D. 2007. Potential role of active vitamin D in retarding the
progression of chronic kidney disease. Nephrol Dial Transplant. 22: 321-328.
39. Tan X, Li Y, and Liu Y. 2007. Therapeutic role and potential mechanisms of active vitamin D in renal
interstitial fibrosis. J. Steroid Biochem. Mol. Biol. 103:491-496.
40. Poncelet AC, Schnaper HW, Tan R, Liu Y, and Runyan CE. 2007. Cell phenotype-specific downregulation of Smad3 involves decreased gene activation as well as protein degradation. J. Biol. Chem.
282: 15534-15540.
41. Li Y, Yang J, Luo JH, Dedhar S, and Liu Y. 2007. Tubular epithelial cell dedifferentiation is driven by
the helix-loop-helix transcription inhibitor Id1. J. Am. Soc. Nephrol. 18: 449-460.
42. Tan R, Zhang X, Yang J, Li Y, and Liu Y. 2007. Molecular basis for the cell type-specific induction of
SnoN expression by hepatocyte growth factor. J. Am. Soc. Nephrol. 18: 2340-2349.
43. Li Y, Dai C, Wu C, and Liu Y. 2007. PINCH-1 promotes tubular epithelial to mesenchymal transition
through interacting with integrin-linked kinase. J. Am. Soc. Nephrol. 18: 2534-2543.
44. Hu K, Wu C, Mars WM, and Liu Y. 2007. Tissue-type plasminogen activator promotes murine
myofibroblast activation through LDL receptor-related protein-1-mediated integrin signaling. J. Clin.
Invest. 117: 3821-3832.
45. Zhang J, Yang J, and Liu Y. 2008. Role of Bcl-xL induction in HGF-mediated renal epithelial cell
survival after oxidant stress. Int. J. Clin. Exp. Pathol. 1: 242-253.
46. Hu K, Lin L, Tan X, Yang J, Bu G, Mars WM, and Liu Y. 2008. Tissue-type plasminogen activator is a
survival factor that protects renal interstitial fibroblasts and myofibroblasts from apoptosis. J. Am. Soc.
Nephrol. 19: 000-000, in press. Doi: 10.1681/ASN.20070303000
68. Li Y, Kang YS, Dai C, Kiss LP, Wen X, and Liu Y. 2008. Epithelial to mesenchymal transition is a
potential pathway leading to podocyte dysfunction and proteinuria. Am. J. Pathol. 172:000-000, in
press. Doi: 10.2353/ajpath.2008.070057
C. Research Support:
Ongoing Research Support:
1 R01 DK071040-01
NIH/NIDDK
Liu (PI)
06/01/05 ~ 05/31/09
Integrin-linked kinase and renal interstitial fibrosis
The major goal of this project is to investigate the role of ILK and its interacting partners in renal interstitial
fibrogenesis.
Role: PI
1 R01 DK61408-04
Liu (PI)
04/01/02 ~ 03/31/10
NIH/NIDDK
HGF gene therapy for chronic renal fibrosis
The major goals of this project are to evaluate the efficacy of HGF gene therapy for chronic renal fibrosis
and to investigate the mechanism underlying HGF inhibition of renal fibrosis.
Role: PI
Completed Research Support:
7-03-RA-54
Liu (PI)
07/01/03 ~ 06/30/06
American Diabetes Association
Therapeutic role of hepatocyte growth factor in diabetic nephropathy
The major goal of this project is to evaluate the efficacy of HGF therapy for diabetes nephropathy.
Role: PI
1 R01 DK064005-03 Liu (PI)
05/01/03 ~ 02/28/07
NIH/NIDDK
Renal myofibroblast: origins, activation and fate
The major goals of this project are to investigate the origins, activation process and fate of renal
myofibroblasts and to design strategies for therapeutic intervention.
Role: PI
2 R01 DK54922-08
Liu (PI)
06/01/03 ~ 5/31/07
NIH/NIDDK
HGF receptor and renal cell survival and differentiation
The major goals of this project are to investigate the role of HGF receptor signaling in renal cell survival and
differentiation.
Role: PI