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 studying how growth factors modulate the kidney's response to injury with a focus on the TGF-beta signaling pathway. TGF-beta is a pleiotropic growth factor that alters many cellular responses (e.g. matrix production, inflammation, apoptosis, proliferation), but the specific response depends upon the target cell type and microenvironment. We use mouse models with the TGF-beta type II receptor deleted in a conditional and inducible manner to investigate how TGF-beta signaling affects the response to injury in a cell-specific fashion. We have a particular interest in how TGF-beta signaling affects the response of proximal tubule epithelium, a key target in human disease, to both acute and chronic injuries. We have generated proximal tubules in vitro which we use to better understand how TGF-beta affects epithelial cell function and the response of cells to other growth factors relevant to injury and repair. Fibroblasts are thought to be the primary cell type responsible for the matrix production comprising fibrosis, the common pathway to end-stage renal disease. We are also investigating fibroblasts' role in tubulointerstitial fibrosis, how their function is altered by growth factors like TGF-beta, and how to better characterize this population of interstitial cells.
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.