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 is detected at early stage.
My research interests have always been the following:
- To identify and develop molecular markers for early disease detection. My previous work identified molecular markers for prediction and progression of CKD in mouse models and validated them using gene expression data from patients with different types of kidney disease. Further study includes evaluation the potential of the predictive marker genes in CKD patients as early diagnostic molecular markers in prospective studies.
- To investigate the underlying pathomechanism of differentially represented markers in CKD. Several of these genes and signaling cascades have not been previously associated with kidney disease. Therefore, I plan to identify their functional roles and associated signaling mechanisms in normal and diseased kidney. These findings will provide new insights into the pathomechanism of renal disease and may open new alleys for early interventional strategies for CKD.
- To provide possible treatment options for patients with potential progression risk. I plan to make use of inhibitors and/or antagonists of early genetic markers to ameliorate or even prevent disease progression primarily in mouse models.
Link to PubMed Citations
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. In Print. J. Am. Soc. Nephrol. 20 (9): 2009.
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.
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.
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.
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.
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.
Ju W, Ogawa A, Heyer J, Nierhof D, Yu L, Schafritz D, Kucherlapati R, and Bottinger E. Smad2 Functions As Negative Regulator of Epithelial-Mesenchymal Transition and Proliferation in Conditional Knockout Mouse Model. Mol. Cell. Biol. 26 (2), 654-667, 2006.
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.
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.
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.
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.