Lauren E. Woodard, Ph.D.Assistant Professor
1161 21st Ave S
Nashville, TN 37232
1) Kidney regeneration
One in seven people in the United States has chronic kidney disease and the ten-year survival rate for patients on dialysis is just ten percent. Dialysis removes toxic waste and volume from the blood but does not replace many important functions of the kidney that regulate muscle mass, cardiovascular health, bone density, blood cells, and blood pressure. Therefore, new therapies are needed that will directly encourage regeneration of the kidney for patients with chronic kidney disease, acute kidney injury, and genetic kidney disorders. We are currently testing new strategies to regenerate the kidney, including in situ reprogramming to an induced nephron progenitor state and use of urine-derived stem cells to deliver genetic payload.
2) Genetic engineering
Transposons are naturally occurring mobile genetic elements. In the lab, we can harness these tools to permanently integrate transgenes into the human genome. The transposase portion is an enzyme that places the transgene into the mammalian genome. We recently found a new way that the transposase can self-regulate through the formation of nuclear rodlet structures. Once the structures appear, transposition ceases. Therefore, investigation into these rodlet structures may hold clues as to how transposons limit integration themselves, with important implications for transposition in both the natural and engineered contexts.
Woodard LE, Welch RC, Williams FM, Luo W, Cheng J, Wilson MH. Hydrodynamic Renal Pelvis Injection for Non-viral Expression of Proteins in the Kidney. J Vis Exp. 2018 Jan 1/8/2018; (131): PMID: 29364221, PMCID: PMC5907682, DOI: 10.3791/56324, ISSN: 1940-087X.
Luo W, Galvan DL, Woodard LE, Dorset D, Levy S, Wilson MH. Comparative analysis of chimeric ZFP-, TALE- and Cas9-piggyBac transposases for integration into a single locus in human cells. Nucleic Acids Res. 2017 Aug 8/21/2017; 45(14): 8411-22. PMID: 28666380, PII: 3897173, DOI: 10.1093/nar/gkx572, ISSN: 1362-4962.
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.
Woodard LE, Downes LM, Lee YC, Kaja A, Terefe ES, Wilson MH. Temporal self-regulation of transposition through host-independent transposase rodlet formation. Nucleic Acids Res [print-electronic]. 2017 Jan 1/9/2017; 45(1): 353-66. PMID: 27899587, PMCID: PMC5224482, PII: gkw1115, DOI: 10.1093/nar/gkw1115, ISSN: 1362-4962.
Woodard LE, Wilson MH. PiggyBac-ing models and new therapeutic strategies. Trends Biotechnol [print-electronic]. 2015 Sep; 33(9): 525-33. PMID: 26211958, PMCID: PMC4663986, PII: S0167-7799(15)00137-7, DOI: 10.1016/j.tibtech.2015.06.009, ISSN: 1879-3096.
Liang M, Woodard LE, Liang A, Luo J, Wilson MH, Mitch WE, Cheng J. Protective role of insulin-like growth factor-1 receptor in endothelial cells against unilateral ureteral obstruction-induced renal fibrosis. Am. J. Pathol [print-electronic]. 2015 May; 185(5): 1234-50. PMID: 25783760, PMCID: PMC4419212, PII: S0002-9440(15)00126-1, DOI: 10.1016/j.ajpath.2015.01.027, ISSN: 1525-2191.
Saha S, Woodard LE, Charron EM, Welch RC, Rooney CM, Wilson MH. Evaluating the potential for undesired genomic effects of the piggyBac transposon system in human cells. Nucleic Acids Res [print-electronic]. 2015 Feb 2/18/2015; 43(3): 1770-82. PMID: 25605795, PMCID: PMC4330379, PII: gkv017, DOI: 10.1093/nar/gkv017, ISSN: 1362-4962.
Patrick RM, Mayberry LK, Choy G, Woodard LE, Liu JS, White A, Mullen RA, Tanavin TM, Latz CA, Browning KS. Two Arabidopsis loci encode novel eukaryotic initiation factor 4E isoforms that are functionally distinct from the conserved plant eukaryotic initiation factor 4E. Plant Physiol [print-electronic]. 2014 Apr; 164(4): 1820-30. PMID: 24501003, PMCID: PMC3982745, PII: pp.113.227785, DOI: 10.1104/pp.113.227785, ISSN: 1532-2548.
Doherty JE, Woodard LE, Bear AS, Foster AE, Wilson MH. An adaptable system for improving transposon-based gene expression in vivo via transient transgene repression. FASEB J [print-electronic]. 2013 Sep; 27(9): 3753-62. PMID: 23752206, PMCID: PMC3752539, PII: fj.13-232090, DOI: 10.1096/fj.13-232090, ISSN: 1530-6860.
Liang A, Wang Y, Woodard LE, Wilson MH, Sharma R, Awasthi YC, Du J, Mitch WE, Cheng J. Loss of glutathione S-transferase A4 accelerates obstruction-induced tubule damage and renal fibrosis. J. Pathol [print-electronic]. 2012 Dec; 228(4): 448-58. PMID: 22711583, PMCID: PMC3760987, DOI: 10.1002/path.4067, ISSN: 1096-9896.
Woodard LE, Li X, Malani N, Kaja A, Hice RH, Atkinson PW, Bushman FD, Craig NL, Wilson MH. Comparative analysis of the recently discovered hAT transposon TcBuster in human cells. PLoS ONE [print-electronic]. 2012; 7(11): e42666. PMID: 23166581, PMCID: PMC3499496, PII: PONE-D-12-05320, DOI: 10.1371/journal.pone.0042666, ISSN: 1932-6203.
Keravala A, Chavez CL, Hu G, Woodard LE, Monahan PE, Calos MP. Long-term phenotypic correction in factor IX knockout mice by using FC31 integrase-mediated gene therapy. Gene Ther [print-electronic]. 2011 Aug; 18(8): 842-8. PMID: 21412285, PII: gt201131, DOI: 10.1038/gt.2011.31, ISSN: 1476-5462.
Chavez CL, Keravala A, Woodard LE, Hillman RT, Stowe TR, Chu JN, Calos MP. Kinetics and longevity of FC31 integrase in mouse liver and cultured cells. Hum. Gene Ther. 2010 Oct; 21(10): 1287-97. PMID: 20497035, PMCID: PMC2974851, DOI: 10.1089/hum.2010.049, ISSN: 1557-7422.
Woodard LE, Hillman RT, Keravala A, Lee S, Calos MP. Effect of nuclear localization and hydrodynamic delivery-induced cell division on phiC31 integrase activity. Gene Ther [print-electronic]. 2010 Feb; 17(2): 217-26. PMID: 19847205, PMCID: PMC2820593, PII: gt2009136, DOI: 10.1038/gt.2009.136, ISSN: 1476-5462.
Woodard LE, Keravala A, Jung WE, Wapinski OL, Yang Q, Felsher DW, Calos MP. Impact of hydrodynamic injection and phiC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma. PLoS ONE. 2010; 5(6): e11367. PMID: 20614008, PMCID: PMC2894073, DOI: 10.1371/journal.pone.0011367, ISSN: 1932-6203.
Keravala A, Lee S, Thyagarajan B, Olivares EC, Gabrovsky VE, Woodard LE, Calos MP. Mutational derivatives of PhiC31 integrase with increased efficiency and specificity. Mol. Ther [print-electronic]. 2009 Jan; 17(1): 112-20. PMID: 19002165, PMCID: PMC2834998, PII: mt2008241, DOI: 10.1038/mt.2008.241, ISSN: 1525-0024.
The laboratory of Dr. Lauren E. Woodard in the Department of Medicine, Division of Nephrology and Hypertension at Vanderbilt University Medical Center in Nashville, TN is currently accepting applications for a Postdoctoral Fellow position. The applicant must have, or be nearing completion of, a Ph.D., M.D., M.D./Ph.D. or equivalent. The successful candidate will work in a highly collaborative environment to conceive experiments, conduct research, and analyze data. It is expected that the successful candidate will travel to and present at conferences, write and edit manuscripts, and carry out multiple projects independently. Our lab has expertise in gene therapy, transposon biology, molecular biology, gene transfer, stem cells, cell therapy, mouse models, kidney injury, renal disease, Cas9, genome modification and transcription factor reprogramming. Candidates with experience in animal trauma models, organoids, entomology, insect tissue culture, bioengineering, synthetic biology, or protein aggregation should mention this in their cover letter. Outstanding applicants are invited to apply regardless of prior research area. Further information may be found here (https://labnodes.vanderbilt.edu/member/profile/id/12496). Please send a CV, list of three references, and a cover letter narrative summarizing relevant experience and career goals to: email@example.com. Vanderbilt University Medical Center is an Equal Opportunity Employer.