Matthew H. Wilson, Ph.D., M.D.

Professor

matthew.wilson@vanderbilt.edu
Faculty Appointments
Professor of Medicine Professor of Cell & Developmental BiologyProfessor of Pharmacology
Education
M.D., Medicine, Vanderbilt University, Nashville, TennesseePh.D., Pharmacology, Vanderbilt University, Nashville, TennesseeB.S., Chemistry, Georgetown College, Georgetown, Kentucky
Office Address
S-3223 MCN
TN 37221
Research Description
Our laboratory uses non-viral gene transfer to ask biological questions relevant to kidney disease and to engineer new therapeutic approaches for kidney disease. We use the piggyBac transposon system (and other transposon systems) for most of our studies.

Currently, our lab is focused on two broad projects. One involves gene-modifying long-lived antigen-specific T cells for cell therapy of anemia. In this strategy, T cells are used as a celluar vehicle to inducibly express erythropoietin (EPO) resulting in drug regulated EPO production. The second broad project involves non-viral gene transfer to kidney directly. We are attempting to phenotypically correct cystinuria in a mouse model of this human disease. The goal is to use gene transfer to express a lacking cystine transporter in proximal tubular cells in vivo. We are also interested in engineering transposons to be more site-directed and efficient in gene transfer applications.
Research Keywords
Harnessing the biology of transposons for gene transfer for kidney disease.
Publications
Reinfeld BI, Madden MZ, Wolf MM, Chytil A, Bader JE, Patterson AR, Sugiura A, Cohen AS, Ali A, Do BT, Muir A, Lewis CA, Hongo RA, Young KL, Brown RE, Todd VM, Huffstater T, Abraham A, O'Neil RT, Wilson MH, Xin F, Tantawy MN, Merryman WD, Johnson RW, Williams CS, Mason EF, Mason FM, Beckermann KE, Vander Heiden MG, Manning HC, Rathmell JC, Rathmell WK. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature [print-electronic]. 2021 May; 593(7858): 282-8. PMID: 33828302, PMCID: PMC8122068, PII: 10.1038/s41586-021-03442-1, DOI: 10.1038/s41586-021-03442-1, ISSN: 1476-4687.

Woodard LE, Williams FM, Jarrett IC, Wilson MH. Functional analysis of the catalytic triad of the hAT-family transposase TcBuster. Plasmid [print-electronic]. 2021 Mar; 114: 102554. PMID: 33476638, PMCID: PMC7946762, PII: S0147-619X(21)00001-9, DOI: 10.1016/j.plasmid.2021.102554, ISSN: 1095-9890.

Love H, Evans R, Humes HD, Roy S, Zent R, Harris R, Wilson M, Fissell WH. Metformin and Inhibition of Transforming Growth Factor-Beta Stimulate In Vitro Transport in Primary Renal Tubule Cells. Tissue Eng Part A. 2020 Oct; 26(19-20): 1091-8. PMID: 32312181, PMCID: PMC7580646, DOI: 10.1089/ten.TEA.2019.0294, ISSN: 1937-335X.

Chiusa M, Hu W, Zienkiewicz J, Chen X, Zhang MZ, Harris RC, Vanacore RM, Bentz JA, Remuzzi G, Benigni A, Fogo AB, Luo W, Mili S, Wilson MH, Zent R, Hawiger J, Pozzi A. EGF receptor-mediated FUS phosphorylation promotes its nuclear translocation and fibrotic signaling. J Cell Biol. 2020 Sep 9/7/2020; 219(9): PMID: 32678881, PMCID: PMC7480104, PII: 151955, DOI: 10.1083/jcb.202001120, ISSN: 1540-8140.

Chen Q, Luo W, Veach RA, Hickman AB, Wilson MH, Dyda F. Structural basis of seamless excision and specific targeting by piggyBac transposase. Nat Commun. 2020 Jul 7/10/2020; 11(1): 3446. PMID: 32651359, PMCID: PMC7351741, PII: 10.1038/s41467-020-17128-1, DOI: 10.1038/s41467-020-17128-1, ISSN: 2041-1723.

Beckermann TM, Welch RC, Williams FM, Mortlock DP, Sha F, Ikizler TA, Woodard LE, Wilson MH. CRISPR/Cas9 engineering of albino cystinuria Type A mice. Genesis [print-electronic]. 2020 May; 58(5): e23357. PMID: 32078250, DOI: 10.1002/dvg.23357, ISSN: 1526-968X.

Wilson MH, Veach RA, Luo W, Welch RC, Roy S, Fissell WH. Genome Engineering Renal Epithelial Cells for Enhanced Volume Transport Function. Cell Mol Bioeng. 2020 Feb; 13(1): 17-26. PMID: 32030105, PMCID: PMC6981331, PII: 601, DOI: 10.1007/s12195-019-00601-3, ISSN: 1865-5025.

Woodard LE, Welch RC, Veach RA, Beckermann TM, Sha F, Weinman EJ, Ikizler TA, Tischfield JA, Sahota A, Wilson MH. Metabolic consequences of cystinuria. BMC Nephrol. 2019 Jun 6/20/2019; 20(1): 227. PMID: 31221135, PMCID: PMC6585015, PII: 10.1186/s12882-019-1417-8, DOI: 10.1186/s12882-019-1417-8, ISSN: 1471-2369.

Vanslambrouck JM, Woodard LE, Suhaimi N, Williams FM, Howden SE, Wilson SB, Lonsdale A, Er PX, Li J, Maksimovic J, Oshlack A, Wilson MH, Little MH. Direct reprogramming to human nephron progenitor-like cells using inducible piggyBac transposon expression of SNAI2-EYA1-SIX1. Kidney Int [print-electronic]. 2019 May; 95(5): 1153-66. PMID: 30827514, PMCID: PMC6478531, PII: S0085-2538(19)30038-9, DOI: 10.1016/j.kint.2018.11.041, ISSN: 1523-1755.

Wilson MH. Consider Changing the Horse for Your CAR-T?. Mol. Ther [print-electronic]. 2018 Aug 8/1/2018; 26(8): 1873-4. PMID: 30078438, PMCID: PMC6094485, PII: S1525-0016(18)30277-6, DOI: 10.1016/j.ymthe.2018.06.018, ISSN: 1525-0024.

Hamada M, Nishio N, Okuno Y, Suzuki S, Kawashima N, Muramatsu H, Tsubota S, Wilson MH, Morita D, Kataoka S, Ichikawa D, Murakami N, Taniguchi R, Suzuki K, Kojima D, Sekiya Y, Nishikawa E, Narita A, Hama A, Kojima S, Nakazawa Y, Takahashi Y. Integration Mapping of piggyBac-Mediated CD19 Chimeric Antigen Receptor T Cells Analyzed by Novel Tagmentation-Assisted PCR. EBioMedicine [print-electronic]. 2018 Aug; 34: 18-26. PMID: 30082227, PMCID: PMC6116345, PII: S2352-3964(18)30251-2, DOI: 10.1016/j.ebiom.2018.07.008, ISSN: 2352-3964.

O'Neil RT, Saha S, Veach RA, Welch RC, Woodard LE, Rooney CM, Wilson MH. Transposon-modified antigen-specific T lymphocytes for sustained therapeutic protein delivery in vivo. Nat Commun. 2018 Apr 4/10/2018; 9(1): 1325. PMID: 29636469, PMCID: PMC5893599, PII: 10.1038/s41467-018-03787-8, DOI: 10.1038/s41467-018-03787-8, ISSN: 2041-1723.

Morita D, Nishio N, Saito S, Tanaka M, Kawashima N, Okuno Y, Suzuki S, Matsuda K, Maeda Y, Wilson MH, Dotti G, Rooney CM, Takahashi Y, Nakazawa Y. Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor in piggyBac Transposon-Engineered T Cells. Mol Ther Methods Clin Dev. 2018 Mar 3/16/2018; 8: 131-40. PMID: 29687032, PMCID: PMC5907825, PII: S2329-0501(17)30128-6, DOI: 10.1016/j.omtm.2017.12.003, ISSN: 2329-0501.

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.

Veach RA, Wilson MH. CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line. PLoS ONE. 2018; 13(9): e0204487. PMID: 30260998, PMCID: PMC6160069, PII: PONE-D-17-41126, DOI: 10.1371/journal.pone.0204487, ISSN: 1932-6203.

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.

Held EP, Iglesia EA, Johnson AS, Fang JY, Wilson MH, Abel TW, Lake W, Siew ED. Neurosarcoidosis Presenting as Aseptic Meningitis in an Immunosuppressed Renal Transplant Recipient. Transplantation. 2016 Oct; 100(10): e96-e100. PMID: 26863472, DOI: 10.1097/TP.0000000000001074, ISSN: 1534-6080.

Nakazawa Y, Matsuda K, Kurata T, Sueki A, Tanaka M, Sakashita K, Imai C, Wilson MH, Koike K. Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34(+) cells of juvenile myelomonocytic leukemia. J Hematol Oncol. 2016 Mar 3/16/2016; 9: 27. PMID: 26983639, PMCID: PMC4793548, PII: 10.1186/s13045-016-0256-3, DOI: 10.1186/s13045-016-0256-3, ISSN: 1756-8722.

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.

Galvan DL, O'Neil RT, Foster AE, Huye L, Bear A, Rooney CM, Wilson MH. Anti-Tumor Effects after Adoptive Transfer of IL-12 Transposon-Modified Murine Splenocytes in the OT-I-Melanoma Mouse Model. PLoS ONE. 2015; 10(10): e0140744. PMID: 26473608, PMCID: PMC4608718, PII: PONE-D-15-17152, DOI: 10.1371/journal.pone.0140744, ISSN: 1932-6203.

Saito S, Nakazawa Y, Sueki A, Matsuda K, Tanaka M, Yanagisawa R, Maeda Y, Sato Y, Okabe S, Inukai T, Sugita K, Wilson MH, Rooney CM, Koike K. Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. Cytotherapy. 2014 Sep; 16(9): 1257-69. PMID: 25108652, PII: S1465-3249(14)00640-9, DOI: 10.1016/j.jcyt.2014.05.022, ISSN: 1477-2566.

Galvan DL, Kettlun CS, Wilson MH. Targeting piggyBac transposon integrations in the human genome. Methods Mol. Biol. 2014; 1114: 143-61. PMID: 24557901, DOI: 10.1007/978-1-62703-761-7_9, ISSN: 1940-6029.

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.

Nakazawa Y, Saha S, Galvan DL, Huye L, Rollins L, Rooney CM, Wilson MH. Evaluation of long-term transgene expression in piggyBac-modified human T lymphocytes. J. Immunother. 2013 Jan; 36(1): 3-10. PMID: 23211626, PMCID: PMC3521868, DOI: 10.1097/CJI.0b013e3182791234, ISSN: 1537-4513.

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.

Doherty JE, Huye LE, Yusa K, Zhou L, Craig NL, Wilson MH. Hyperactive piggyBac gene transfer in human cells and in vivo. Hum. Gene Ther [print-electronic]. 2012 Mar; 23(3): 311-20. PMID: 21992617, PMCID: PMC3300075, DOI: 10.1089/hum.2011.138, ISSN: 1557-7422.

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.

Saha S, Nakazawa Y, Huye LE, Doherty JE, Galvan DL, Rooney CM, Wilson MH. PiggyBac transposon system modification of primary human T cells. J Vis Exp. 2012; (69): e4235. PMID: 23149543, PMCID: PMC3514050, PII: 4235, DOI: 10.3791/4235, ISSN: 1940-087X.

Huye LE, Nakazawa Y, Patel MP, Yvon E, Sun J, Savoldo B, Wilson MH, Dotti G, Rooney CM. Combining mTor inhibitors with rapamycin-resistant T cells: a two-pronged approach to tumor elimination. Mol. Ther [print-electronic]. 2011 Dec; 19(12): 2239-48. PMID: 21878902, PMCID: PMC3242659, PII: mt2011179, DOI: 10.1038/mt.2011.179, ISSN: 1525-0024.

Nakazawa Y, Huye LE, Salsman VS, Leen AM, Ahmed N, Rollins L, Dotti G, Gottschalk SM, Wilson MH, Rooney CM. PiggyBac-mediated cancer immunotherapy using EBV-specific cytotoxic T-cells expressing HER2-specific chimeric antigen receptor. Mol. Ther [print-electronic]. 2011 Dec; 19(12): 2133-43. PMID: 21772253, PMCID: PMC3242651, PII: mt2011131, DOI: 10.1038/mt.2011.131, ISSN: 1525-0024.

Kettlun C, Galvan DL, George AL, Kaja A, Wilson MH. Manipulating piggyBac transposon chromosomal integration site selection in human cells. Mol. Ther [print-electronic]. 2011 Sep; 19(9): 1636-44. PMID: 21730970, PMCID: PMC3182353, PII: mt2011129, DOI: 10.1038/mt.2011.129, ISSN: 1525-0024.

Wang J, Wang Y, Long J, Chang BH, Wilson MH, Overbeek P, Danesh FR. Tamoxifen-inducible podocyte-specific iCre recombinase transgenic mouse provides a simple approach for modulation of podocytes in vivo. Genesis. 2010 Jul; 48(7): 446-51. PMID: 20641128, PMCID: PMC3014324, DOI: 10.1002/dvg.20635, ISSN: 1526-968X.

Manuri PV, Wilson MH, Maiti SN, Mi T, Singh H, Olivares S, Dawson MJ, Huls H, Lee DA, Rao PH, Kaminski JM, Nakazawa Y, Gottschalk S, Kebriaei P, Shpall EJ, Champlin RE, Cooper LJ. PiggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies. Hum. Gene Ther. 2010 Apr; 21(4): 427-37. PMID: 19905893, PMCID: PMC2938363, DOI: 10.1089/hum.2009.114, ISSN: 1557-7422.

Kahlig KM, Saridey SK, Kaja A, Daniels MA, George AL, Wilson MH. Multiplexed transposon-mediated stable gene transfer in human cells. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Jan 1/26/2010; 107(4): 1343-8. PMID: 20080581, PMCID: PMC2824351, PII: 0910383107, DOI: 10.1073/pnas.0910383107, ISSN: 1091-6490.

Wilson MH, George AL. Designing and testing chimeric zinc finger transposases. Methods Mol. Biol. 2010; 649: 353-63. PMID: 20680846, DOI: 10.1007/978-1-60761-753-2_22, ISSN: 1940-6029.

Saridey SK, Liu L, Doherty JE, Kaja A, Galvan DL, Fletcher BS, Wilson MH. PiggyBac transposon-based inducible gene expression in vivo after somatic cell gene transfer. Mol. Ther [print-electronic]. 2009 Dec; 17(12): 2115-20. PMID: 19809403, PMCID: PMC2814386, PII: mt2009234, DOI: 10.1038/mt.2009.234, ISSN: 1525-0024.

Nakazawa Y, Huye LE, Dotti G, Foster AE, Vera JF, Manuri PR, June CH, Rooney CM, Wilson MH. Optimization of the PiggyBac transposon system for the sustained genetic modification of human T lymphocytes. J. Immunother. 2009 Oct; 32(8): 826-36. PMID: 19752751, PMCID: PMC2796278, DOI: 10.1097/CJI.0b013e3181ad762b, ISSN: 1537-4513.

Galvan DL, Nakazawa Y, Kaja A, Kettlun C, Cooper LJ, Rooney CM, Wilson MH. Genome-wide mapping of PiggyBac transposon integrations in primary human T cells. J. Immunother. 2009 Oct; 32(8): 837-44. PMID: 19752750, PMCID: PMC2796288, DOI: 10.1097/CJI.0b013e3181b2914c, ISSN: 1537-4513.

Wilson MH, Coates CJ, George AL. PiggyBac transposon-mediated gene transfer in human cells. Mol. Ther. 2007 Jan; 15(1): 139-45. PMID: 17164785, PII: 6300028, DOI: 10.1038/sj.mt.6300028, ISSN: 1525-0024.

Wilson MH, Kaminski JM, George AL. Functional zinc finger/sleeping beauty transposase chimeras exhibit attenuated overproduction inhibition. FEBS Lett [print-electronic]. 2005 Nov 11/7/2005; 579(27): 6205-9. PMID: 16243318, PII: S0014-5793(05)01239-1, DOI: 10.1016/j.febslet.2005.10.004, ISSN: 0014-5793.

Johnson KB, Serwint JR, Fagan LM, Thompson RE, Wilson MH. Computer-based documentation: effect on parent and physician satisfaction during a pediatric health maintenance encounter. Arch Pediatr Adolesc Med. 2005 Mar; 159(3): 250-4. PMID: 15753268, PII: 159/3/250, DOI: 10.1001/archpedi.159.3.250, ISSN: 1072-4710.

O'Brochta DA, Sethuraman N, Wilson R, Hice RH, Pinkerton AC, Levesque CS, Bideshi DK, Jasinskiene N, Coates CJ, James AA, Lehane MJ, Atkinson PW. Gene vector and transposable element behavior in mosquitoes. J. Exp. Biol. 2003 Nov; 206(Pt 21): 3823-34. PMID: 14506218, ISSN: 0022-0949.

Tan CM, Wilson MH, MacMillan LB, Kobilka BK, Limbird LE. Heterozygous alpha 2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Sep 9/17/2002; 99(19): 12471-6. PMID: 12205290, PMCID: PMC129469, PII: 122368499, DOI: 10.1073/pnas.122368499, ISSN: 0027-8424.

Wilson MH, Highfield HA, Limbird LE. The role of a conserved inter-transmembrane domain interface in regulating alpha(2a)-adrenergic receptor conformational stability and cell-surface turnover. Mol. Pharmacol. 2001 Apr; 59(4): 929-38. PMID: 11259639, ISSN: 0026-895X.

Wilson MH, Limbird LE. Mechanisms regulating the cell surface residence time of the alpha 2A-adrenergic receptor. Biochemistry. 2000 Feb 2/1/2000; 39(4): 693-700. PMID: 10651634, PII: bi9920275, ISSN: 0006-2960.

Wilson MH, Puranam RS, Ottman R, Gilliam C, Limbird LE, George AL, McNamara JO. Evaluation of the alpha(2A)-adrenergic receptor gene in a heritable form of temporal lobe epilepsy. Neurology. 1998 Dec; 51(6): 1730-1. PMID: 9855534, ISSN: 0028-3878.

Available Postdoctoral Position Details
Posted: 8/29/2022

NIH funded postdoctoral positions are available for research in developing cell and gene therapies for kidney diseases. Individuals with a strong background in molecular biology, cell culture, and a willingness to work with animals are encouraged to apply. The researcher will learn a variety of novel techniques for in vivo and ex vivo gene transfer including transposon technology, CRISPR/Cas9, and adeno-associated viral (AAV) vectors. Current projects are focused on developing a cell therapy for Fabry disease, engineering new AAV vectors, and advancing non-viral genome engineering and gene delivery technologies.

Interested applicants can contact Dr. Wilson directly for consideration at matthew.wilson@vumc.org