David M. Bader, Ph.D.

Professor

david.bader@vanderbilt.edu
Faculty Appointments
Professor of Medicine Professor of Cell and Developmental BiologyGladys Parkinson Stahlman Chair in Cardiovascular Research
Education
Ph.D., Anatomy, University of North Dakota, Williston, North DakotaB.A., Biology & Chemistry, Augustana College , Sioux Falls, South Dakota
Office Address
346 PRB
2220 Pierce AVenue
Nashville, TN 37232-6300
Research Description
The work in our laboratory has focused on the commitment, differentiation and function of cardiac and vascular cells in the embryo. The early heart development and vasculogenesis provide excellent systems to examine fundamental issues in developmental biology. Heart development involves the commitment of embryogenic cells to the cardiogenic mesodermal lineage, coordinated activation of cell-specific genes in committed cells, and the diversification of progenitors in a highly patterned manner leading to the generation of distinct myogenic phenotypes.

Our current work is focused on the function of two genes that were discovered in our laboratory and analysis of the conserved system whereby coelomates generate vessels to organs during development.

LEK1 is a large and complex protein that regulates proliferation and differentiation of cardiac myocytes.
Through a series of biochemical, morphological, genetic and cell biological experiments, we have determined that LEK1 proteins function in cell movement, trafficking and division through its interaction with Rb proteins, the cytoskeleton and the SNARE complex. Our ongoing work is focused on conditionally inhibiting the function of this gene in developing mice and continuing our studies of LEK1 interaction with subcellular domains.

Bves is an integral membrane protein discovered by former members of the lab. This protein is essential for proper cell/cell interaction during coronary vessel development. Our work has shown that Bves is one of the first proteins trafficked to points of cell/cell contact and that it associates with cytoplasmic proteins that regulate cell/cell adhesion, process formation and movement. Our goal is to determine how disruption of Bves function impacts embryonic development in vertebrate and invertebrate development.

Lastly, we have determined that blood vessel formation to internal organs has a conserved program that is been overlooked heretofore. We have discovered that vasculogenesis to the heart and gut is linked to the formation of the embryonic coelom and that progenitors of these blood vessels arise via a mechanism unlike that of the body wall and limbs. We are now disrupting this developmental system in an effort to understand the cellular and molecular mechanisms driving this process.
Research Keywords
Bves, Lek1, development, heart, cell adhesion, cell migration, cytoskeleton, organogensis
Publications
Pfaltzgraff ER, Shelton EL, Galindo CL, Nelms BL, Hooper CW, Poole SD, Labosky PA, Bader DM, Reese J. Embryonic domains of the aorta derived from diverse origins exhibit distinct properties that converge into a common phenotype in the adult. J. Mol. Cell. Cardiol [print-electronic]. 2014 Apr; 69: 88-96. PMID: 24508561, PMCID: PMC4034360, PII: S0022-2828(14)00036-4, DOI: 10.1016/j.yjmcc.2014.01.016, ISSN: 1095-8584.

Benesh EC, Miller PM, Pfaltzgraff ER, Grega-Larson NE, Hager HA, Sung BH, Qu X, Baldwin HS, Weaver AM, Bader DM. Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition. Mol. Biol. Cell [print-electronic]. 2013 Nov; 24(22): 3496-510. PMID: 24048452, PMCID: PMC3826988, PII: mbc.E12-07-0539, DOI: 10.1091/mbc.E12-07-0539, ISSN: 1939-4586.

Shelton EL, Poole SD, Reese J, Bader DM. Omental grafting: a cell-based therapy for blood vessel repair. J Tissue Eng Regen Med [print-electronic]. 2013 Jun; 7(6): 421-33. PMID: 22318999, PMCID: PMC3672266, DOI: 10.1002/term.528, ISSN: 1932-7005.

Shelton EL, Galindo CL, Williams CH, Pfaltzgraff E, Hong CC, Bader DM. Autotaxin signaling governs phenotypic heterogeneity in visceral and parietal mesothelia. PLoS ONE [electronic-print]. 2013; 8(7): e69712. PMID: 23936085, PMCID: PMC3723636, PII: PONE-D-13-15224, DOI: 10.1371/journal.pone.0069712, ISSN: 1932-6203.

Thomason RT, Bader DM, Winters NI. Comprehensive timeline of mesodermal development in the quail small intestine. Dev. Dyn [print-electronic]. 2012 Nov; 241(11): 1678-94. PMID: 22930586, PMCID: PMC3475750, DOI: 10.1002/dvdy.23855, ISSN: 1097-0177.

Shelton EL, Bader DM. Thymosin ß4 mobilizes mesothelial cells for blood vessel repair. Ann. N. Y. Acad. Sci. 2012 Oct; 1269: 125-30. PMID: 23045980, PMCID: PMC3693742, DOI: 10.1111/j.1749-6632.2012.06713.x, ISSN: 1749-6632.

Winters NI, Thomason RT, Bader DM. Identification of a novel developmental mechanism in the generation of mesothelia. Development [print-electronic]. 2012 Aug; 139(16): 2926-34. PMID: 22764055, PMCID: PMC3403102, PII: dev.082396, DOI: 10.1242/dev.082396, ISSN: 1477-9129.

Dees E, Miller PM, Moynihan KL, Pooley RD, Hunt RP, Galindo CL, Rottman JN, Bader DM. Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy. Dis Model Mech [print-electronic]. 2012 Jul; 5(4): 468-80. PMID: 22563055, PMCID: PMC3380710, PII: dmm.008680, DOI: 10.1242/dmm.008680, ISSN: 1754-8411.

Cross EE, Thomason RT, Martinez M, Hopkins CR, Hong CC, Bader DM. Application of small organic molecules reveals cooperative TGFß and BMP regulation of mesothelial cell behaviors. ACS Chem. Biol [print-electronic]. 2011 Sep 9/16/2011; 6(9): 952-61. PMID: 21740033, PMCID: PMC3177035, DOI: 10.1021/cb200205z, ISSN: 1554-8937.

Russ PK, Pino CJ, Williams CS, Bader DM, Haselton FR, Chang MS. Bves modulates tight junction associated signaling. PLoS ONE. 2011; 6(1): e14563. PMID: 21283798, PMCID: PMC3024319, DOI: 10.1371/journal.pone.0014563, ISSN: 1932-6203.

Hager HA, Roberts RJ, Cross EE, Proux-Gillardeaux V, Bader DM. Identification of a novel Bves function: regulation of vesicular transport. EMBO J [print-electronic]. 2010 Feb 2/3/2010; 29(3): 532-45. PMID: 20057356, PMCID: PMC2830705, PII: emboj2009379, DOI: 10.1038/emboj.2009.379, ISSN: 1460-2075.

Karunamuni G, Yang K, Doughman YQ, Wikenheiser J, Bader D, Barnett J, Austin A, Parsons-Wingerter P, Watanabe M. Expression of lymphatic markers during avian and mouse cardiogenesis. Anat Rec (Hoboken). 2010 Feb; 293(2): 259-70. PMID: 19938109, PMCID: PMC3607319, DOI: 10.1002/ar.21043, ISSN: 1932-8494.

Moynihan KL, Pooley R, Miller PM, Kaverina I, Bader DM. Murine CENP-F regulates centrosomal microtubule nucleation and interacts with Hook2 at the centrosome. Mol. Biol. Cell [print-electronic]. 2009 Nov; 20(22): 4790-803. PMID: 19793914, PMCID: PMC2777108, PII: E09-07-0560, DOI: 10.1091/mbc.E09-07-0560, ISSN: 1939-4586.

Hager HA, Bader DM. Bves: ten years after. Histol. Histopathol. 2009 Jun; 24(6): 777-87. PMID: 19337975, PMCID: PMC2853719, ISSN: 1699-5848.

Yang K, Doughman YQ, Karunamuni G, Gu S, Yang YC, Bader DM, Watanabe M. Expression of active Notch1 in avian coronary development. Dev. Dyn. 2009 Jan; 238(1): 162-70. PMID: 19097050, PMCID: PMC2929638, DOI: 10.1002/dvdy.21811, ISSN: 1058-8388.

Pooley RD, Moynihan KL, Soukoulis V, Reddy S, Francis R, Lo C, Ma LJ, Bader DM. Murine CENPF interacts with syntaxin 4 in the regulation of vesicular transport. J. Cell. Sci [print-electronic]. 2008 Oct 10/15/2008; 121(Pt 20): 3413-21. PMID: 18827011, PMCID: PMC2849733, PII: jcs.032847, DOI: 10.1242/jcs.032847, ISSN: 0021-9533.

Smith TK, Hager HA, Francis R, Kilkenny DM, Lo CW, Bader DM. Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Jun 6/17/2008; 105(24): 8298-303. PMID: 18541910, PMCID: PMC2423412, PII: 0802345105, DOI: 10.1073/pnas.0802345105, ISSN: 1091-6490.

Robertson JB, Zhu T, Nasreen S, Kilkenny D, Bader D, Dees E. CMF1-Rb interaction promotes myogenesis in avian skeletal myoblasts. Dev. Dyn. 2008 May; 237(5): 1424-33. PMID: 18425850, PMCID: PMC2854498, DOI: 10.1002/dvdy.21544, ISSN: 1058-8388.

Kawaguchi M, Hager HA, Wada A, Koyama T, Chang MS, Bader DM. Identification of a novel intracellular interaction domain essential for Bves function. PLoS ONE. 2008; 3(5): e2261. PMID: 18493308, PMCID: PMC2373926, DOI: 10.1371/journal.pone.0002261, ISSN: 1932-6203.

Robertson, J.B., Zhu, T., Nasreen, S., Kilenny, D., Bader, D., and Dees, E.. CMF1-Rb interaction promotes myogenesis in avain skeletal myoblasts. Dev Dyn. 2008; 237: 1424-33.

Kawaguchi M, Bader DM, Wilm B. Serosal mesothelium retains vasculogenic potential. Dev. Dyn. 2007 Nov; 236(11): 2973-9. PMID: 17948313, PMCID: PMC2853712, DOI: 10.1002/dvdy.21334, ISSN: 1058-8388.

Smith TK, Bader DM. Signals from both sides: Control of cardiac development by the endocardium and epicardium. Semin. Cell Dev. Biol [print-electronic]. 2007 Feb; 18(1): 84-9. PMID: 17267246, PMCID: PMC2849752, PII: S1084-9521(06)00141-8, DOI: 10.1016/j.semcdb.2006.12.013, ISSN: 1084-9521.

Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G, Kantz J, Chen Z, Carr C, Jerome WG, Chen J, Baldwin HS, Nicholson W, Bader DM, Jetton T, Gannon M, Powers AC. Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes. 2006 Nov; 55(11): 2974-85. PMID: 17065333, PII: 55/11/2974, DOI: 10.2337/db06-0690, ISSN: 0012-1797.

Dees E, Robertson JB, Zhu T, Bader D. Specific deletion of CMF1 nuclear localization domain causes incomplete cell cycle withdrawal and impaired differentiation in avian skeletal myoblasts. Exp. Cell Res [print-electronic]. 2006 Oct 10/1/2006; 312(16): 3000-14. PMID: 16904105, PII: S0014-4827(06)00212-6, DOI: 10.1016/j.yexcr.2006.06.027, ISSN: 0014-4827.

Pooley RD, Reddy S, Soukoulis V, Roland JT, Goldenring JR, Bader DM. CytLEK1 is a regulator of plasma membrane recycling through its interaction with SNAP-25. Mol. Biol. Cell [print-electronic]. 2006 Jul; 17(7): 3176-86. PMID: 16672379, PMCID: PMC1483049, PII: E05-12-1127, DOI: 10.1091/mbc.E05-12-1127, ISSN: 1059-1524.

Smith TK, Bader DM. Characterization of Bves expression during mouse development using newly generated immunoreagents. Dev. Dyn. 2006 Jun; 235(6): 1701-8. PMID: 16538658, PMCID: PMC4678624, DOI: 10.1002/dvdy.20739, ISSN: 1058-8388.

Osler ME, Smith TK, Bader DM. Bves, a member of the Popeye domain-containing gene family. Dev. Dyn. 2006 Mar; 235(3): 586-93. PMID: 16444674, PMCID: PMC2849751, DOI: 10.1002/dvdy.20688, ISSN: 1058-8388.

Ripley AN, Osler ME, Wright CV, Bader D. Xbves is a regulator of epithelial movement during early Xenopus laevis development. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2006 Jan 1/17/2006; 103(3): 614-9. PMID: 16407138, PMCID: PMC1334639, PII: 0506095103, DOI: 10.1073/pnas.0506095103, ISSN: 0027-8424.

Dees, E., Robertson, J.B., Zhu, T., and Bader, D.. Specific deletion of CMF1 nuclear localization domain causes incomplete cell cycle withdrawal and impaired differentiation in avian skeletal myoblasts. Exp Cell Res. 2006; 312: 3000-14.

Wilm B, Ipenberg A, Hastie ND, Burch JB, Bader DM. The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development. 2005 Dec; 132(23): 5317-28. PMID: 16284122, PII: 132/23/5317, DOI: 10.1242/dev.02141, ISSN: 0950-1991.

Osler ME, Chang MS, Bader DM. Bves modulates epithelial integrity through an interaction at the tight junction. J. Cell. Sci [print-electronic]. 2005 Oct 10/15/2005; 118(Pt 20): 4667-78. PMID: 16188940, PII: jcs.02588, DOI: 10.1242/jcs.02588, ISSN: 0021-9533.

Dees E, Robertson JB, Ashe M, Pabón-Peña LM, Bader D, Goodwin RL. LEK1 protein expression in normal and dysregulated cardiomyocyte mitosis. Anat Rec A Discov Mol Cell Evol Biol. 2005 Sep; 286(1): 823-32. PMID: 16047383, DOI: 10.1002/ar.a.20221, ISSN: 1552-4884.

Soukoulis V, Reddy S, Pooley RD, Feng Y, Walsh CA, Bader DM. Cytoplasmic LEK1 is a regulator of microtubule function through its interaction with the LIS1 pathway. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Jun 6/14/2005; 102(24): 8549-54. PMID: 15939891, PMCID: PMC1150833, PII: 0502303102, DOI: 10.1073/pnas.0502303102, ISSN: 0027-8424.

Ripley AN, Chang MS, Bader DM. Bves is expressed in the epithelial components of the retina, lens, and cornea. Invest. Ophthalmol. Vis. Sci. 2004 Aug; 45(8): 2475-83. PMID: 15277466, PII: 45/8/2475, DOI: 10.1167/iovs.04-0013, ISSN: 0146-0404.

Osler ME, Bader DM. Bves expression during avian embryogenesis. Dev. Dyn. 2004 Mar; 229(3): 658-67. PMID: 14991721, DOI: 10.1002/dvdy.10490, ISSN: 1058-8388.

Wada AM, Willet SG, Bader D. Coronary vessel development: a unique form of vasculogenesis. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2003 Dec; 23(12): 2138-45. PMID: 14525796, PII: 01.ATV.0000098645.38676.CC, DOI: 10.1161/01.ATV.0000098645.38676.CC, ISSN: 1524-4636.

Knight RF, Bader DM, Backstrom JR. Membrane topology of Bves/Pop1A, a cell adhesion molecule that displays dynamic changes in cellular distribution during development. J. Biol. Chem [print-electronic]. 2003 Aug 8/29/2003; 278(35): 32872-9. PMID: 12815060, PII: M301961200, DOI: 10.1074/jbc.M301961200, ISSN: 0021-9258.

Wada AM, Smith TK, Osler ME, Reese DE, Bader DM. Epicardial/Mesothelial cell line retains vasculogenic potential of embryonic epicardium. Circ. Res [print-electronic]. 2003 Mar 3/21/2003; 92(5): 525-31. PMID: 12600887, PII: 01.RES.0000060484.11032.0B, DOI: 10.1161/01.RES.0000060484.11032.0B, ISSN: 1524-4571.

Nesset AL, Bader DM. Hole is a novel gene product expressed in the developing heart and brain. Mech. Dev. 2002 Sep; 117(1-2): 347-50. PMID: 12204283, PII: S0925477302002137, ISSN: 0925-4773.

Wada AM, Reese DE, Bader DM. Bves: prototype of a new class of cell adhesion molecules expressed during coronary artery development. Development. 2001 Jun; 128(11): 2085-93. PMID: 11493530, ISSN: 0950-1991.

Dees E, Pabón-Peña LM, Goodwin RL, Bader D. Characterization of CMF1 in avian skeletal muscle. Dev. Dyn. 2000 Oct; 219(2): 169-81. PMID: 11002337, PII: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1055>3.0.CO;2-B, DOI: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1055>3.0.CO;2-B, ISSN: 1058-8388.

Pabón-Peña LM, Goodwin RL, Cise LJ, Bader D. Analysis of CMF1 reveals a bone morphogenetic protein-independent component of the cardiomyogenic pathway. J. Biol. Chem. 2000 Jul 7/14/2000; 275(28): 21453-9. PMID: 10747923, PII: M000518200, DOI: 10.1074/jbc.M000518200, ISSN: 0021-9258.

Croissant JD, Carpenter S, Bader D. Identification and genomic cloning of CMHC1. A unique myosin heavy chain expressed exclusively in the developing chicken heart. J. Biol. Chem. 2000 Jan 1/21/2000; 275(3): 1944-51. PMID: 10636896, ISSN: 0021-9258.

Reese DE, Bader DM. Cloning and expression of hbves, a novel and highly conserved mRNA expressed in the developing and adult heart and skeletal muscle in the human. Mamm. Genome. 1999 Sep; 10(9): 913-5. PMID: 10441744, PII: MG99-644, ISSN: 0938-8990.

Goodwin RL, Pabón-Peña LM, Foster GC, Bader D. The cloning and analysis of LEK1 identifies variations in the LEK/centromere protein F/mitosin gene family. J. Biol. Chem. 1999 Jun 6/25/1999; 274(26): 18597-604. PMID: 10373470, ISSN: 0021-9258.

Reese DE, Zavaljevski M, Streiff NL, Bader D. Bves: A novel gene expressed during coronary blood vessel development. Dev. Biol. 1999 May 5/1/1999; 209(1): 159-71. PMID: 10208750, PII: S0012-1606(99)99246-1, DOI: 10.1006/dbio.1999.9246, ISSN: 0012-1606.

Gannon M, Bader D. Avian cardiac progenitors: methods for isolation, culture, and analysis of differentiation. Methods Cell Biol. 1997; 52: 117-32. PMID: 9379947, ISSN: 0091-679X.

Wei, Y., Bader, D., and Litvin, J. Identification of a cardiac-specific transcript essential for myocyte differentiation. 1996.

Eisenberg, C. and Bader, D. Establishment of a mesodermal cell line QCE-6. Circulation Research. 1996; 78: 205-16.

Gannon, M. and Bader, D. Initiation of cardiac differentiation occurs in the absence of anterior endoderm. 1995.

Yutzey, K.E., Gannon. M., and Bader, D. Diversification of cardiomyogenic cell lineages in vitro. 1995.

Melnik, N. And Bader, D. Commitment, Differentiation, & Diversification of Avian Cardiac progenitor Cells. Annuals New York Academy of Sciences. 1995; 27((752)): 1-8.

Yutzey, K. and Bader, D. Diversification of cardiomyogenic cell lineages during early heart development. Circ. Res. 1995; 77: 216-9.

Eisenberg, C. and Bader, D. QCE-6: A clonal cell line with cardiac and endothelial cell potentials. Dev. Biol. 1995; 167: 469-81.

Yutzey, K.E., Rhee, J.T,, and Bader, D. Expression of the atrial-specific myosin heavy chain AMHC1 and the establishment of anteroposterior polarity in the developing chicken heart. 1994.

Montgomery, M.O., Litvin, J., Gonzalez-Sanchez, A., and Bader, D. In vitro analysis of the cardiomyogenic cell lineage. Dev. Biol. 1994; 164: 63-70.

Litvin, J., Montgomery, M.O., Goldhamer, D., Emerson, C.P., and Bader, D. Identification of DNA-binding protein(s) in the developing heart. Devel. Biol. 1993; 156: 409-17.

Han, Y.S., Dennis, J.E., Cohen-Gould, L., Bader, D., and Fischman, D.A. The expression and distribution of sarcomeric myosin in the presumptive myocardium of early chicken embryos. Dev. Dyn. 1992; 193: 257-65.

Bisaha, J.G. and Bader, D. Isolation and characterization of a ventricular-specific avian myosin heavy chain, VMHC1: Expression in differentiating cardiac and skeletal muscle. Devel. Biol. 1991; 148: 355-64.

Gonzalez-Sanchez, A. and D. Bader. In vitro analysis of cardiac progenitor cell differentiation. Devel. Biol. 1990; 139: 197-209.

Zhang, Y., S.A.Shafiq, and D. Bader. Detection of ventricular myosin heavy chain throughout cardiac myogenesis in the chicken heart. J. Cell Biol. 1986; 102: 1480-4.

Zadeh, B.J., A. Gonzalez-Sanchez, D.A. Fischman, and D. Bader. Myosin heavy chain expression in embryonic cardiac cell cultures. Dev. Biol. 1986; 115: 204-14.

Gonzalez-Sanchez, A. and D. Bader. Characterization of myosin heavy chain in myocardial cells of the conductive system of the chicken heart. J. Cell Biol. 1985; 100: 270-5.

Gonzalez-Sanchez, A. and D. Bader. Immunochemical analysis of myosin heavy chains in the developing chicken heart. Develop. Biol. 1984; 103: 151-8.

Bader, D.M., T. Masaki and D.A. Fischman. Immunochemical analysis of myosin heavy chains during avian myogenesis in vivo and in vitro. J. Cell Biol. 1982; 95((3)): 763-70.

Bader, D. and J.O. Oberpriller. Autoradiographic and electron microscopic studies of minced cardiac muscle regeneration in the adult newt (Notophthalmus viridescens). J. Exp. Zool. 1979; 208: 177-93.

Bader, D. and J.O. Oberpriller. Repair and reorganization of cardiac muscle grafts in the adult newt (Notophthalmus viridescens). J. Morph. 1978; 155: 349-58.