生物医学工程系学术报告8.23(报告人：Wenjun Ju, Ph.D)
发布时间: 2010-08-23 11:29:00
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北京大学工学院 生物医学工程系学术报告 |
报告一题目：Identification and Validation of Molecular Marker for Chronic Kidney disease
报告人 Wenjun Ju, Ph.D.
Research Assistant Professor,
Department of Internal Medicine-Nephrology,
University of Michigan, Ann Arbor, MI
主持人：葛子钢 特聘研究员
时间：8月23日（周一）下午3:00
地点：廖凯原楼2-102会议室
CURRICULUM VITAE
Wenjun Ju, Ph.D.
Research Assistant Professor of Internal Medicine/Nephrology
University of Michigan
1150 West Medical Center Drive
1552 MSRBII
Ann Arbor, MI 48109-0676
Tel. (001) 734-615-0480
Fax. (001) 734-763-0982
Wenjunj（at）med.umich.edu
EDUCATION:
1987-91 B.Sc. Beijing Normal University, Beijing, China
1991-94 M.Sc Beijing Normal University Graduate School, Beijing, China
1995-99 Ph.D. Helmholtz Centre for Infection Research Center (previous Geselschaft fuer Biotechnologische Forschung (GBF) & Technische Universität Braunschweig, Braunschweig, Germany
POSTDOCTORAL TRAINING:
4/1999-1/2004 Research Associate, Department of Medicine, Division of Nephrology,
Albert Einstein College of Medicine, Bronx, NY
ACADEMIC APPOINTMENTS:
2/2004-6/2009 Research Assistant Professor, Department of Medicine, Division of Nephrology,
Mount Sinai School of Medicine, New York, NY
7/2009-present Research Assistant Professor, Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI
TEACHING EXPERIENCE:
2001-2004 Supervisor for MD PhD student
2005-2008 Supervisor for PhD student
2001-2009 Supervisor for technicians and lab manager
RESEARCH INTERESTS: Chronic kidney diseases (CKD) affect millions of people in the United States. It can lead to end-stage renal disease (ESRD) requiring dialysis and renal replacement therapy, associated with high cost, morbidity and mortality. Decline of kidney function can be delayed and patient outcomes can be positively improved if disease progression could be predicted at early stage.
My research interests are the following:
1. To identify and develop molecular markers correlated with CKD progression. With established national and international multicenter collaboration, we generated molecular signatures of various nephropathies, including: diabetic nephropathy (DN), hypertensive nephropathy (HTN), focal segmental glomerulosclerosis (FSGS), Minimal change disease (MCN), lupus nephritis (SLE), IgA Nephropathy (IgAN), thin membrane disease (TMD), rapid progressive glomerulonephritis (RPGN). With computational and bioinformatics resources available, I will identify common molecular markers for kidney disease progression. In the mean time, I also aim at identifying disease specific markers for molecular diagnosis and interventional guidance.
2. To prospectively test the identified candidate markers in archival renal biopsies from independent cohorts of CKD patients to determine the predictive power of those markers for long-term renal disease course.
3. I strongly pursue the minimally invasive way of CKD diagnosis and progression prediction. The ideal biomarker for experimental studies and clinical applications is minimally invasive. A major barrier in defining robust markers is the multiple, non-renal confounders influencing mRNA and protein levels in body fluids. I will apply approach that limits the influence by evaluating kidney tissue-derived markers for associated alterations in blood and urine. Complimentary proteomic and antibody-based strategies will be used to characterize proteins from blood and urine.
4. Most importantly, I am interested in the pathomechanism that is underlying the bio-network. In-depth understanding of the molecular pathways involved in CKD disease progression will be able to provide interventional strategies by targeting altered signaling pathways thereby ameliorate or prevent disease progression.
GRANTS:
Co-Investigator:
Active:
Molecular Predictors of Progressive Renal Failure in the Chronic Renal Insufficiency
5R01DK079912-02 07/15/2008-06/30/2013
PI: Matthias Kretzler, Co-investigator: Ju W
Our specific aims will extract the most effective non-invasive, accurate and sensitive biomarkers from available expression profiles taking advantage of the unique design of CRIC: In Aim 1 candidate mRNA markers of renal function will be extracted from already available renal biopsy gene expression data using biostatistical modeling tools. In Aim 2 these candidate markers will be prospectively evaluated in CRIC biopsies to test their power for predicting the primary endpoint of CRIC (i.e. decline of renal function over time measured as slope of GFR). In Aim 3 non-invasive markers of CRI will be extracted from the kidney tissue-derived predictors using parallel studies in plasma, urine and leukocyte samples from the same patients studied in Aim 2. In Aim 4 the full CRIC cohort will be analyzed to test the strength of the non-invasive marker panel and define effects of age, race, renal function and diabetes on the prediction of progressive CRI. Combining the molecular datasets from renal biopsy profiling study of CRI with the power of a prospectively followed cohort of CRI patients presents the opportunity to fundamentally alter the way we define and manage CRI. Using intra-renal gene expression profiles to guide the identification of non-invasive molecular diagnostic targets will focus the study on the most promising biomarker candidates for risk stratification of CRI. We anticipate that this study will be a crucial step of a transition from a "one size fits all" management of CRI towards an approach valuing the molecular individuality of each kidney
HONORS/AWARDS:
7/2001 – 6/2003 American Heart Association (AHA), Research Fellowship Award
“Role of Smad2 in TGF-β signaling in atherosclerotic lesions”
MEMBERSHIPS IN PROFESSIONAL SOCIETIES:
2005-present American Society of Nephrology
EXTRAMURAL INVITED PRESENTATIONS
1. Expression Monitoring in a Transgenic Model of progressive Glomeruosclerosis. 2001
Renal week - American Society of Nephrology (ASN), Toronto, Canada.
2. Dickkopf-3 (dkk3) is a Podocyte-Restricted TGF beta Target Gene Expressed in Mice with Progressive kidney disease. 2002
Renal week - American Society of Nephrology (ASN), Philadelphia, PA.
3. Hepatocyte-specific deletion of Smad2 in mouse indicates inhibitory roles in hepatocytes growth and EMT. 2005
Annual Meeting for American Association of Cancer Research. Anaheim, Orange County, California, USA.
4. Characterization of Diagnostic and Predictive Marker Gene Candidates in Mouse Models of Progressive Kidney Disease. 2007
Renal week - American Society of Nephrology (ASN), San Francisco, CA.
5. TGF beta Signaling, A Window to Look into Progressive Chronic Kidney Disease. Renal Grand Rounds, Miller School of Medicine, University of Miami. 2008
6. A novel molecular predictor of glomerular filtration rate in patients with chronic kidney disease. 2008
Renal week - American Society of Nephrology (ASN), Philadelphia, PA.
AD HOC REVIEWER FOR:
Kidney International
Clinical Journal of the American Society of Nephrology
BIBLIOGRAPHY:
Publications in Scientific Journals
Peer-Reviewed
1.Ju W, Yin L, Wang D. The effect of the reorganization of Microfilaments on activity of PKII and PKA. J. Beijing Normal Univ. (Nature Science), Vol. 31, No. 1, 1995.
2. Ju W and Wang DS. Effects of microfilamentous depolymerization by cytochalasin B on cAMP-PKA pathway. Chinese Science Bulletin 41 (8): 684-, 1996.
3. Ju W and Wang DS. Localization of the mRNA of early genes along cytoskeleton. Chinese Science Bulletin 42 (19): 1655-, 1997.
4. Kaps C, Lauber J, Ju W, Czichos S and Gross G. The recombinant expression of bone morphogenetic protein type IA receptor (Alk3) in mesenchymal progenitors C3H10T1/2 is sufficient for osteo-/chondrogenic development. Biochem Soc Transactions 26: 27-332, 1997.
5.Gross,G., Czichos,S., Ju,W., Kaps,C., Häupl,T., Sittinger,M., Burmester,G., and Hoffmann,A. Signalkaskaden bei der Knorpel- und Knochenbildung. Zeitschrift für Rheumatologie 59, 406-407, 2000.
6. Bottinger E, Ju W, and Zavadil J. Application of Microarrays in Renal Biology and Medicine. Exp. Nephrol 10: 93-101, 2002.
7. Ju W, Hoffman A, Verschueren K, Tylzanowski P, Kaps C, Gross G and Huylebroeck D. The Bone Morphogenetic Protein 2 signaling mediator Smad1 participates predominantly in osteogenic but not in chondrogenic differentiation in mesenchymal progenitors C3HT10T1/2. J Bone & Mineral Res 15(10): 1889-99, 2000.
8. Piek E, Ju W, Heyer J, Escalante-Alcalde D, Stewart CL, Weinstein M, Deng C, Kucherlapati R, Böttinger EP, and Roberts AB. Functional Characterization of TGF-beta signaling in mouse embryonic fibroblasts lacking expression of Smad2 or Smad3: Differential roles for Smad2 and Smad3 in TGF-beta signal transduction. J Biol Chem. 276(23): 19945-532001, 2001.
9. Blush J, Lei J, Ju W, Silbiger S, Pullman J, and Neugarten J. Estradiol reverses renal injury in Alb/TGF-beta1 transgenic mice. Kidney Int. 66(6):2148-54, 2004.
10. Wu D, Bitzer M, Ju W , Mundel P, and Böttinger E. TGF- β Concentration Specifies Differential Signaling Profiles of Growth Arrest/Differentiation and Apoptosis in Podocytes. J. Am. Soc. Nephrol. 16(11): 3211-21, 2005.
11. Wang W, Huang XR, Canlas E, Oka K, Truong LD, Deng C, Bhowmick NA, Ju W, Bottinger E, Lan HY. TGF-b Dependent and Independent Smad Signaling Pathways in Angiotensin II-Induced Vascular Sclerosis: Essential Role of Smad3. Circ. Res. 98(8):1032-9. 2006.
12. Klein J, Ju W, Heyer J, Witte B, Knaus P, Kucherlapati R, Bottinger E, Nitschke L, and Kneitz B. B cell-specific deficiency for SMAD2 in vivo leads to defects in TGF-β directed IgA switching and changes in B-cell fate. J. Immunol. 176 (4): 2389-2396. 2006.
13. Ju W, Ogawa A, Heyer J, Nierhof D, Yu L, Schafritz D, Kucherlapati R, and Bottinger E. Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. Mol. Cell. Biol. 26 (2), 654-667, 2006.
14. Krick S, Shi S, Ju W, Mundel P, and Bottinger E. Mpv17l Protects against Mitochondrial Oxidative Stress and Apoptosis by Activation of Omi/HtrA2 protease. Proc. Natl. Acad. Sci. U.S.A, 105(37), 14106-14111, 2008.
15. Hoot K, Lighthall J, Lu S, Han G, Li A, Ju W, Kulesz-Martin M, Bottinger E, Wang XJ. Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. J. Clin. Invest. 118(8) 2722-2732, 2008.
16. Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger E, Reid P, Levy D and Bromberg J. Epigenetic regulation of Foxp3 expression and regulatory T cells by DNA methyltransferase. J. Immunol. 182(1):259-73, 2009.
17. Ju W, Eichinger F, Bitzer M, Oh J, McWeeney S, Berthier C, Shedden K, Cohen C, Henger A, Krick S, Kopp J, Stoeckert C, Dikman S, Schröppel B, Thomas D, Schlondorff D, Kretzler M and Bottinger E. Renal Gene and Protein Expression Signatures for Prediction of Kidney Disease Progression. Am. J. Pathol. 174 (6): 2073-2085, 2009.
18. Xavier S, Niranjan T, Krick S, Zhang T, Ju W, Shaw A, Schiffer M, and Bottinger E. TGFBRI Independently Activates Smad- and CD2APDependent Pathways in Podocytes. J. Am. Soc. Nephrol. 20 (10):2127-2137, 2009.
19. Meng X, Huang X, Chung A , Wei Q, Shao X, Igarashi P, Ju W, Bottinger E, and Lan HY. Smad2 protects against TGF-β/Smad3-mediated renal fibrosis in vivo and in vitro. J. Am. Soc. Nephrol. Accepted, 2010.
20. Ju W and Brosius F. Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species. Accepted. Seminars in Nephrology, 2010
BOOK CHAPTERS:
1.Bottinger E & Ju W. Gene expression signatures of Tgf-beta/ Smad-induced responses, Chapter 17 of Smad Signal Transduction • Smads in Proliferation, Differentiation and Disease. Dijke, P.t., Heldin, C.-H. (Eds.), Vol. 5, ISBN 978-1-4020-4542-4, 2006.
MANUSCRIPTS IN PREPARATION:
1. Zhang R, Ju W, Vigneau C, Dikman S, Gordon R, Vlassara H, Striker GE, Zheng F. Increased Susceptibility to Endoplasmic Reticulum Stress Injury in the Aging. Am. J. Pathol.
2. Ju W, Gruhn W, Wu D, Zhang T, Schiffer M, Rastaldi M, Bitzer M, Cohen C, Kretzler M, and Böttinger E. Dickkopf-3 is Associated with Kidney Disease Progression and Protects Podocytes from TGF Beta Induced Apoptosis
PUBLISHED ABSTRACTS (PRESENTATIONS):
1. Ju W, The C-terminal domain of SMAD1, a signaling mediator for the bone morphogenetic protein 2 (BMP2), is sufficient for osteo/chondrogenic development in mesenchymal progenitors (C3H10T1/2). Cellular Signal Transduction Meeting, Jena, Germany, September 26 – 28, 1997. (Poster)
2.Ju W, Piek E, Heyer J, Roberts A, Kucherlapatti R, and Bottinger EP. Differential Roles of Smad2 and Smad3 in Regulation of Cell Growth and Gene Expression by TGF-beta. J. Am. Soc. Nephrol 2000, Vol 11, pp 457A-457A
3. Sharma K, Liang D, Wu D, Dunn SR, Zhu Y, Ju W, and Bottinger EP. Gene Expression Profiling In Mouse Models of Diabetic Nephropathy. J. Am. Soc. Nephrol 2001, Vol 12, pp 847A-847A, A4435
4. Bitzer M, Ju W, Yu LP, Roberts AB and Bottinger EP. Smad3 Mediates Progressive Renal Disease in Transforming Growth Factor-b1 (TGF-b1) Transgenic Mice. J. Am. Soc. Nephrol 2001, Vol 12, pp 672A-672A A3498
5. Ju W, Bitzer M, Liang D, Zavadil J, Zhang W, and Bottinger EP. Candidate Genes for Initiation of Progressive Glomerulosclerosis and Tubulo-Interstitial Fibrosis in TGF-b1 Transgenic Mice Identified by Functional Genomics Screens. J. Am. Soc. Nephrol 2001, Vol 12, pp 706A-706A, A3682
6. Woroniecki RP, Suztak K, Bitzer M, Ju W, Cermak L, Kaskel F, and Bottinger E. Laser Capture Microdissection (LCM) and Quantitative rt-PCR (qrt-PCR) for Isolated Glomerular and Tubular Model of Progressive Glomerular Sclerosis., J. Am. Soc. Nephrol 2002, Vol 13, Iss S, pp A118-A119 (589KL)
7. Susztak K, Wyckoff J, Ju W, Condeelis J, and Bottinger E. Real time in Vivo Multiphoton Imaging of Mouse Renal Cortex. ), J. Am. Soc. Nephrol 2002, Vol 13, Iss S, pp A118-A118 (589KL)
8. Bitzer M, Wu D, Ju W, Mundel P, and Bottinger E. Deletion of Smad3 Alters Phenotype and TGF-beta Responsiveness of Podocytes. Role of GADD45-Family Members. ), J. Am. Soc. Nephrol 2002, (Oral Presentation SA-FC160)
9. Bitzer M, Ju W, Yu L, Roberts A, and Bottinger E. TGF- β1 signaling in Glomerularsclerosis. ASCI /AAP joint meeting. 2002.
10. Ju W, Bitzer M, McWeeney S, Liang D, Yu L, Stoeckert C, and Bottinger E. Functional Genomics of TGF-β/SMAD Signaling in Murine Kidney Disease. Gorden Conference 2002.
11.Blush JA, Lei J, Pullman J, Ju W, Bottinger EP, Silbiger S, Neugarten J. Estrodial Ameliorates Progressive Renal Injury in Alb/TGF-Transgenic Mice. J. Am. Soc. Nephrol 2003. (Oral Presentation F-FC085)
12. Ju W, Bitzer M, Oh J, Yu LP, Boettinger EP. Predictive Genes for Progressive Kidney Fibrosis in Transforming Growth Factor-Beta 1 (TGF-b) Transgenic Mice. J. Am. Soc. Nephrol 2003 [SA-PO344]
13.Wang W, Huang X, Hou C, Liu F, Ju W, Shao X, Oka K, Igarashi P, Bottinger E, Lan H. A Novel Approach for Generating Conditional Knockout Mice Using Ultrasound-Mediated-Cre-LoxP Technique. J. Am. Soc. Nephrol 2004 [SA-PO546]
14. Kohn E, Du Z, Ju W, Bottinger E, and Wakefield L. Smad3 gene dosage differentially impacts a variety of TGF-β-mediated biological responses in the mammary epithelium. Roles of TGF-beta in Disease Pathogenesis: Novel Therapeutic Strategies (C4), Keystone, Colorado, USA. 2005
15. Ju W, Ogawa A, Heyer J, Yu L, Schafritz D, Kucherlapati R, and Bottinger E. Smad2 Negativly Regulates Epithelial-Mesenchymal-Transition and Proliferation in Mouse Liver Hepatocytes. Roles of TGF-beta in Disease Pathogenesis: Novel Therapeutic Strategies (C4), Keystone, Colorado, USA. 2005
16.Ju W, Rastaldi MP, Kretzler M, and Böttinger E. Correlation of Dickkopf3 expression with type II diabetic nephropathy. 6th International Podocyte Conference, Helsinki, Finland. 2006.
17. Xavier S, Niranjan T, Krick S, Schiffer M, Ju W, Bottinger E. Cd2-Associated Protein (Cd2ap) Interacts with Cytoplasmic Transforming Growth Factor beta (TGF ) Receptor Type1 (TGF R1) through Its C-Terminal Region and Functions as the Essential Molecular Linker Mediating Activation of Anti-Apoptotic Phosphoinositide 3-OH Kinase-Dependent AKT Survival by TGF in Podocytes and Tubular Epithelial Cells. J. Am. Soc. Nephrol 2006, TH- FC-009
18. Bitzer M, Siconolfi-Baez L, Ju W, Bottinger E, Angeletti R, Hostetter T. Urinary Proteome Alterations in Chronic Fibrotic Kidney Disease Induced by TGF-b. J. Am. Soc. Nephrol 2006, F FC-015
19. Ju W, Rastaldi M, Kretzler M, Bottinger E. et al, Correlation of Dickkopf3 Expression with Type II Diabetic Nephropathy, J. Am. Soc. Nephrol 2006, SA-PO370
20. Krick S, Shi S, Ju W, and Bottinger E. The Mpv17-Like Protein, a Homolog of Mpv17, Is a Novel Mitochondrial Membrane Protein That Protects Proximal Tubular Epithelial Cells Against ROS-Induced Mitochondrial Dysfunction and Apoptosis. J. Am. Soc. Nephrol 2007, F-FC039.
21. Jing X, Ju W, Kopp J, Zavadil J, and Bitzer M. Role of mir-21 in Transforming Growth Factor-beta Induced Renal Injury. J. Am. Soc. Nephrol 2007, F-PO346.
22. Jing X, Ju W, Shang, H, Kim M, Kopp J, Esau C and Bitzer M. Role of miR-21 in renal injury. J. Am. Soc. Nephrol 2008.
23. Bitzer M, Juan L, Rosenfeld G, Kim M, Ju W, Hostetter T, and Fazzari M. Early mRNA Expression and Splicing Events Induced by Uninephrectomy. J. Am. Soc. Nephrol 2009, F-PO1833.
24. Bitzer M, Ju W, Jing X, Angeletti R, and Lim J. Role of microRNA-21and New Target Genes in Glomerular Homeostasis. J. Am. Soc. Nephrol 2009, TH-PO797.
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