Leslie Stuart Gewin, M.D.

Assistant Professor

l.gewin@vanderbilt.edu
Faculty Appointments
Assistant Professor of Medicine Assistant Professor of Cell and Developmental Biology
Education
M.D., Medicine, University of Alabama, Birmingham, AlabamaB.A., Princeton University, Princeton, New Jersey
Office Address
1161 21st Avenue South
MCN S-3223
Nashville, TN 37232
Research Description
The Gewin laboratory is interested in the pathophysiology of renal injury and tubulointerstitial fibrosis with a specific interest in tubule epithelial injury. Renal tubule epithelial cells, particularly proximal tubules, are both vulnerable to kidney injury but also play an important role in the progression of chronic kidney disease. Our group is focused on understanding how growth factors, particularly the TGF-beta and Wnt/beta-catenin pathways, modulate the epithelial response to injury. We use mouse models with renal tubule-specific alterations in these growth factor pathways and study how those altered pathways affect the response to injury. The Gewin laboratory is also interested in alterations in metabolism, cell cycle, and mitochondrial function in the injured proximal tubule and how TGF-beta and Wnt/beta-catenin affect these responses to stress. In addition to in vivo models, we use cell culture and molecular biology techniques to better define mechanisms of injury. By improving our understanding of epithelial repair mechanisms, we hope to identify better targets for the treatment of chronic kidney disease.
Research Keywords
Growth factors, Fibrosis, Epithelial biology
Publications
Gewin LS. Renal fibrosis: Primacy of the proximal tubule. Matrix Biol [print-electronic]. 2018 Feb 2/6/2018; PMID: 29425694, PII: S0945-053X(17)30412-2, DOI: 10.1016/j.matbio.2018.02.006, ISSN: 1569-1802.

Gewin LS. Renal Tubule Repair: Is Wnt/ß-Catenin a Friend or Foe?. Genes (Basel). 2018 Jan 1/24/2018; 9(2): PMID: 29364168, PMCID: PMC5852554, PII: genes9020058, DOI: 10.3390/genes9020058, ISSN: 2073-4425.

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. Blocking TGF-ß and ß-Catenin Epithelial Crosstalk Exacerbates CKD. J. Am. Soc. Nephrol [print-electronic]. 2017 Jul 7/12/2017; PMID: 28701516, PII: ASN.2016121351, DOI: 10.1681/ASN.2016121351, ISSN: 1533-3450.

Overstreet JM, Wang Y, Wang X, Niu A, Gewin LS, Yao B, Harris RC, Zhang MZ. Selective activation of epidermal growth factor receptor in renal proximal tubule induces tubulointerstitial fibrosis. FASEB J [print-electronic]. 2017 Jun 6/16/2017; PMID: 28626027, PII: fj.201601359RR, DOI: 10.1096/fj.201601359RR, ISSN: 1530-6860.

Woodard LE, Cheng J, Welch RC, Williams FM, Luo W, Gewin LS, Wilson MH. Kidney-specific transposon-mediated gene transfer in vivo. Sci Rep. 2017 Mar 3/20/2017; 7: 44904. PMID: 28317878, PMCID: PMC5357952, PII: srep44904, DOI: 10.1038/srep44904, ISSN: 2045-2322.

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. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-a-induced apoptosis in vivo. Mol. Syst. Biol. 2015 Oct 10/30/2015; 11(10): 835. PMID: 26519361, PMCID: PMC4631206, ISSN: 1744-4292.

Neelisetty S, Alford C, Reynolds K, Woodbury L, Nlandu-Khodo S, Yang H, Fogo AB, Hao CM, Harris RC, Zent R, Gewin L. Renal fibrosis is not reduced by blocking transforming growth factor-ß signaling in matrix-producing interstitial cells. Kidney Int [print-electronic]. 2015 Sep; 88(3): 503-14. PMID: 25760325, PMCID: PMC4556568, PII: ki201551, DOI: 10.1038/ki.2015.51, ISSN: 1523-1755.

Zhang MZ, Wang Y, Yao B, Gewin L, Wei S, Capdevila JH, Harris RC. Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney. Am. J. Physiol. Renal Physiol [print-electronic]. 2013 Dec 12/15/2013; 305(12): F1680-6. PMID: 24154693, PMCID: PMC3882452, PII: ajprenal.00409.2013, DOI: 10.1152/ajprenal.00409.2013, ISSN: 1522-1466.

Wallace E, Gewin L. Imatinib: novel treatment of immune-mediated kidney injury. J. Am. Soc. Nephrol [print-electronic]. 2013 Apr; 24(5): 694-701. PMID: 23431076, PII: ASN.2012080818, DOI: 10.1681/ASN.2012080818, ISSN: 1533-3450.

Gewin L, Vadivelu S, Neelisetty S, Srichai MB, Paueksakon P, Pozzi A, Harris RC, Zent R. Deleting the TGF-ß receptor attenuates acute proximal tubule injury. J. Am. Soc. Nephrol [print-electronic]. 2012 Dec; 23(12): 2001-11. PMID: 23160515, PMCID: PMC3507360, PII: ASN.2012020139, DOI: 10.1681/ASN.2012020139, ISSN: 1533-3450.

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. ß1 integrin NPXY motifs regulate kidney collecting-duct development and maintenance by induced-fit interactions with cytosolic proteins. Mol. Cell. Biol [print-electronic]. 2012 Oct; 32(20): 4080-91. PMID: 22869523, PMCID: PMC3457338, PII: MCB.00568-12, DOI: 10.1128/MCB.00568-12, ISSN: 1098-5549.

Gewin L, Zent R. How does TGF-ß mediate tubulointerstitial fibrosis?. Semin. Nephrol. 2012 May; 32(3): 228-35. PMID: 22835453, PII: S0270-9295(12)00061-7, DOI: 10.1016/j.semnephrol.2012.04.001, ISSN: 1558-4488.

Srichai MB, Colleta H, Gewin L, Matrisian L, Abel TW, Koshikawa N, Seiki M, Pozzi A, Harris RC, Zent R. Membrane-type 4 matrix metalloproteinase (MT4-MMP) modulates water homeostasis in mice. PLoS ONE. 2011; 6(2): e17099. PMID: 21347258, PMCID: PMC3037967, DOI: 10.1371/journal.pone.0017099, ISSN: 1932-6203.

Gewin L, Bulus N, Mernaugh G, Moeckel G, Harris RC, Moses HL, Pozzi A, Zent R. TGF-beta receptor deletion in the renal collecting system exacerbates fibrosis. J. Am. Soc. Nephrol [print-electronic]. 2010 Aug; 21(8): 1334-43. PMID: 20576806, PMCID: PMC2938601, PII: ASN.2010020147, DOI: 10.1681/ASN.2010020147, ISSN: 1533-3450.

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. Beta1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity. Development [print-electronic]. 2009 Oct; 136(19): 3357-66. PMID: 19710172, PMCID: PMC2739149, PII: dev.036269, DOI: 10.1242/dev.036269, ISSN: 1477-9129.

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. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity. Dev. Biol [print-electronic]. 2008 Apr 4/15/2008; 316(2): 288-301. PMID: 18328474, PMCID: PMC2396524, PII: S0012-1606(08)00039-0, DOI: 10.1016/j.ydbio.2008.01.022, ISSN: 1095-564X.

Available Postdoctoral Position Details
Posted: 10/2/2018

The Gewin laboratory in VUMC’s Division of Nephrology is looking for a postdoctoral candidate with a strong background in rodent models of injury or epithelial injury and molecular biology techniques (e.g. qPCR, immunoblotting, cell culture). Experience working with mitochondria, confocal microscopy, and metabolism, though not required, is preferred. The postdoc will work on federally-funded projects that investigate how growth factors (TGF-beta, Wnt/beta-catenin) affect epithelial responses to injury such as cell cycle changes, mitochondrial injury, and altered metabolism. These epithelial cell responses to injury will be investigated to better understand the pathophysiology of renal fibrosis and tubular atrophy.