Contact Information
Vanderbilt Center for Kidney Disease Vanderbilt Division of Nephrology S-3223 Medical Center North Nashville, TN 37232-2372 615 322-2150 (phone) 615 343-2675 (fax)
Leslie Stuart Gewin MD
Department: Medicine
Biography
My research focuses on understanding how growth factors (e.g. TGF-beta, Wnt/beta-catenin) modulate the renal response to acute and chronic injury. Growth factors such as TGF-beta mediate different cellular effects depending upon the target cell type. As the epithelial cells are often the target of renal injury, we have used the Cre/lox system to generate mice lacking various growth factors and transcription factors specifically in renal tubules. In addition, we have generated specific cell populations in vitro to better understand how growth factors affect cell cycle progression, mitochondrial function, and other cellular responses. I was previously funded by a VA Career Development Award and now have NIH funding to investigate growth factors and renal epithelial injury.
Featured Publications
1. The many talents of transforming growth factor-β in the kidney.
Gewin L (2019) Curr Opin Nephrol Hypertens ():
Citation ⋅ 30893214 (PubMed)2. Novel kidney dissociation protocol and image-based flow cytometry facilitate improved analysis of injured proximal tubules.
Manolopoulou M, Matlock BK, Nlandu Khodo S, Simmons AJ, Lau KS, Phillips-Mignemi M, Ivanova A, Alford CE, Flaherty DK, Gewin LS (2019) Am J Physiol Renal Physiol ():
Citation ⋅ 30759021 (PubMed)3. Peroxidasin and eosinophil peroxidase, but not myeloperoxidase, contribute to renal fibrosis in the murine unilateral ureteral obstruction model.
Colon S, Luan H, Liu Y, Meyer C, Gewin L, Bhave G (2019) Am J Physiol Renal Physiol 316(2): F360-F371
Citation ⋅ 30565999 (PubMed) PMC6397377 (PubMed Central)Publications
1. The many talents of transforming growth factor-β in the kidney.
Gewin L (2019) Curr Opin Nephrol Hypertens ():
Citation ⋅ 30893214 (PubMed)2. Novel kidney dissociation protocol and image-based flow cytometry facilitate improved analysis of injured proximal tubules.
Manolopoulou M, Matlock BK, Nlandu Khodo S, Simmons AJ, Lau KS, Phillips-Mignemi M, Ivanova A, Alford CE, Flaherty DK, Gewin LS (2019) Am J Physiol Renal Physiol ():
Citation ⋅ 30759021 (PubMed)3. Peroxidasin and eosinophil peroxidase, but not myeloperoxidase, contribute to renal fibrosis in the murine unilateral ureteral obstruction model.
Colon S, Luan H, Liu Y, Meyer C, Gewin L, Bhave G (2019) Am J Physiol Renal Physiol 316(2): F360-F371
Citation ⋅ 30565999 (PubMed) PMC6397377 (PubMed Central)4. Substrate Elasticity Governs Differentiation of Renal Tubule Cells in Prolonged Culture.
Love HD, Ao M, Jorgensen S, Swearingen L, Ferrell NJ, Evans RC, Gewin L, Harris RC, Zent R, Roy S, Fissell WH (2018) Tissue Eng Part A ():
Citation ⋅ 30484388 (PubMed)5. TGF-β promotes fibrosis after severe acute kidney injury by enhancing renal macrophage infiltration.
Chung S, Overstreet JM, Li Y, Wang Y, Niu A, Wang S, Fan X, Sasaki K, Jin GN, Khodo SN, Gewin L, Zhang MZ, Harris RC (2018) JCI Insight 3(21):
Citation ⋅ 30385721 (PubMed) PMC6238749 (PubMed Central)6. Renal fibrosis: Primacy of the proximal tubule.
Gewin LS (2018) Matrix Biol 68-69(): 248-262
Citation ⋅ 29425694 (PubMed) PMC6015527 (PubMed Central)7. Renal Tubule Repair: Is Wnt/β-Catenin a Friend or Foe?
Gewin LS (2018) Genes (Basel) 9(2):
Citation ⋅ 29364168 (PubMed) PMC5852554 (PubMed Central)8. Blocking TGF- and -Catenin Epithelial Crosstalk Exacerbates CKD.
Nlandu-Khodo S, Neelisetty S, Phillips M, Manolopoulou M, Bhave G, May L, Clark PE, Yang H, Fogo AB, Harris RC, Taketo MM, Lee E, Gewin LS (2017) J Am Soc Nephrol 28(12): 3490-3503
Citation ⋅ 28701516 (PubMed) PMC5698068 (PubMed Central)9. Selective activation of epidermal growth factor receptor in renal proximal tubule induces tubulointerstitial fibrosis.
Overstreet JM, Wang Y, Wang X, Niu A, Gewin LS, Yao B, Harris RC, Zhang MZ (2017) FASEB J 31(10): 4407-4421
Citation ⋅ 28626027 (PubMed) PMC5602893 (PubMed Central)10. Kidney-specific transposon-mediated gene transfer in vivo.
Woodard LE, Cheng J, Welch RC, Williams FM, Luo W, Gewin LS, Wilson MH (2017) Sci Rep 7(): 44904
Citation ⋅ 28317878 (PubMed) PMC5357952 (PubMed Central)11. Pharmacologic Blockade of v1 Integrin Ameliorates Renal Failure and Fibrosis .
Chang Y, Lau WL, Jo H, Tsujino K, Gewin L, Reed NI, Atakilit A, Nunes ACF, DeGrado WF, Sheppard D (2017) J Am Soc Nephrol 28(7): 1998-2005
Citation ⋅ 28220032 (PubMed) PMC5491273 (PubMed Central)12. Integrin alpha6 maintains the structural integrity of the kidney collecting system.
Viquez OM, Yazlovitskaya EM, Tu T, Mernaugh G, Secades P, McKee KK, Georges-Labouesse E, De Arcangelis A, Quaranta V, Yurchenco P, Gewin LC, Sonnenberg A, Pozzi A, Zent R (2017) Matrix Biol 57-58(): 244-257
Citation ⋅ 28043890 (PubMed) PMC5330664 (PubMed Central)13. Progression of chronic kidney disease: too much cellular talk causes damage.
Gewin L, Zent R, Pozzi A (2017) Kidney Int 91(3): 552-560
Citation ⋅ 27773427 (PubMed) PMC5313325 (PubMed Central)14. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-α-induced apoptosis in vivo.
Simmons AJ, Banerjee A, McKinley ET, Scurrah CR, Herring CA, Gewin LS, Masuzaki R, Karp SJ, Franklin JL, Gerdes MJ, Irish JM, Coffey RJ, Lau KS (2016) Mol Syst Biol 12(8): 881
Citation ⋅ 27574014 (PubMed) PMC5119492 (PubMed Central)15. NO clue to pathogenesis of aristolochic acid nephropathy.
Gewin L (2016) Exp Physiol 101(1): 33
Citation ⋅ 26782267 (PubMed)16. Deleting the TGF-β receptor in proximal tubules impairs HGF signaling.
Nlandu Khodo S, Neelisetty S, Woodbury L, Green E, Harris RC, Zent R, Gewin L (2016) Am J Physiol Renal Physiol 310(6): F499-510
Citation ⋅ 26739889 (PubMed) PMC4796273 (PubMed Central)17. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-α-induced apoptosis in vivo.
Simmons AJ, Banerjee A, McKinley ET, Scurrah CR, Herring CA, Gewin LS, Masuzaki R, Karp SJ, Franklin JL, Gerdes MJ, Irish JM, Coffey RJ, Lau KS (2015) Mol Syst Biol 11(10): 835
Citation ⋅ 26519361 (PubMed) PMC4631206 (PubMed Central)18. Renal fibrosis is not reduced by blocking transforming growth factor-β signaling in matrix-producing interstitial cells.
Neelisetty S, Alford C, Reynolds K, Woodbury L, Nlandu-Khodo S, Yang H, Fogo AB, Hao CM, Harris RC, Zent R, Gewin L (2015) Kidney Int 88(3): 503-14
Citation ⋅ 25760325 (PubMed) PMC4556568 (PubMed Central)19. Integrin-mediated type II TGF-β receptor tyrosine dephosphorylation controls SMAD-dependent profibrotic signaling.
Chen X, Wang H, Liao HJ, Hu W, Gewin L, Mernaugh G, Zhang S, Zhang ZY, Vega-Montoto L, Vanacore RM, Fässler R, Zent R, Pozzi A (2014) J Clin Invest 124(8): 3295-310
Citation ⋅ 24983314 (PubMed) PMC4109532 (PubMed Central)20. Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney.
Zhang MZ, Wang Y, Yao B, Gewin L, Wei S, Capdevila JH, Harris RC (2013) Am J Physiol Renal Physiol 305(12): F1680-6
Citation ⋅ 24154693 (PubMed) PMC3882452 (PubMed Central)21. Imatinib: novel treatment of immune-mediated kidney injury.
Wallace E, Gewin L (2013) J Am Soc Nephrol 24(5): 694-701
Citation ⋅ 23431076 (PubMed)22. Deleting the TGF-β receptor attenuates acute proximal tubule injury.
Gewin L, Vadivelu S, Neelisetty S, Srichai MB, Paueksakon P, Pozzi A, Harris RC, Zent R (2012) J Am Soc Nephrol 23(12): 2001-11
Citation ⋅ 23160515 (PubMed) PMC3507360 (PubMed Central)23. β1 integrin NPXY motifs regulate kidney collecting-duct development and maintenance by induced-fit interactions with cytosolic proteins.
Mathew S, Lu Z, Palamuttam RJ, Mernaugh G, Hadziselimovic A, Chen J, Bulus N, Gewin LS, Voehler M, Meves A, Ballestrem C, Fässler R, Pozzi A, Sanders CR, Zent R (2012) Mol Cell Biol 32(20): 4080-91
Citation ⋅ 22869523 (PubMed) PMC3457338 (PubMed Central)24. How does TGF-β mediate tubulointerstitial fibrosis?
Gewin L, Zent R (2012) Semin Nephrol 32(3): 228-35
Citation ⋅ 22835453 (PubMed) PMC4948283 (PubMed Central)25. Membrane-type 4 matrix metalloproteinase (MT4-MMP) modulates water homeostasis in mice.
Srichai MB, Colleta H, Gewin L, Matrisian L, Abel TW, Koshikawa N, Seiki M, Pozzi A, Harris RC, Zent R (2011) PLoS One 6(2): e17099
Citation ⋅ 21347258 (PubMed) PMC3037967 (PubMed Central)26. TGF-beta receptor deletion in the renal collecting system exacerbates fibrosis.
Gewin L, Bulus N, Mernaugh G, Moeckel G, Harris RC, Moses HL, Pozzi A, Zent R (2010) J Am Soc Nephrol 21(8): 1334-43
Citation ⋅ 20576806 (PubMed) PMC2938601 (PubMed Central)27. beta1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity.
Zhang X, Mernaugh G, Yang DH, Gewin L, Srichai MB, Harris RC, Iturregui JM, Nelson RD, Kohan DE, Abrahamson D, Fässler R, Yurchenco P, Pozzi A, Zent R (2009) Development 136(19): 3357-66
Citation ⋅ 19710172 (PubMed) PMC2739149 (PubMed Central)28. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity.
Pozzi A, Jarad G, Moeckel GW, Coffa S, Zhang X, Gewin L, Eremina V, Hudson BG, Borza DB, Harris RC, Holzman LB, Phillips CL, Fassler R, Quaggin SE, Miner JH, Zent R (2008) Dev Biol 316(2): 288-301
Citation ⋅ 18328474 (PubMed) PMC2396524 (PubMed Central)