Vanderbilt University School of Medicine

Baldwin, H. Scott , M.D.
Professor of Pediatrics
Katrina Overall McDonald Chair in Pediatrics
Professor of Cell and Developmental Biology

Lab Url: N/A

Phone Number: 615-322-2703


Baldwin, H. Scott's picture

Office Address   Mailing Address

9435-A MRB IV-Langford

9435-A MRB IV-Langford 2213 Garland Ave 37232-0493

Research Keywords
endothelial cells heart development vascular development valve development angiogenesis vasculogenesis genetics,Developmental biology,Gene regulation,Gene therapy,Genetics,Heart,Human Genetics,Knockout,Molecular medicine,Mouse,Pulmonary,Stem cells,Transcription factor,Vascular Biology

Research Specialty
Delineating the molecular basis of vascular development in the mammalian embryo as an approach to understanding the etiology of congenital heart diseases.

Research Description
My research efforts have concentrated on delineating the molecular basis of vascular development in the mammalian embryo as an approach to understanding the etiology of congenital heart diseases. My laborotory efforts are based on the hypothesis that the developing vasculature provides important patterning information that directs subsequent cardiac and pulmonary morphogenetic events. We have focused our investigation on two areas: 1) the role of endothelial cell adhesion molecules, particularly PECAM-1 in regulating vascular ontogeny and 2) the role of NFATc-1, in specification of endocardial development during early organogenesis. PECAM-1/CD31 is the earliest endothelial specific adhesion molecule expressed in the developing embryo. In addition, it is expressed as multiple alternatively spliced isoforms which demonstrate dramatically different adhesion profiles. We are using in vitro cell culture, in situ whole mouse embryo culture, and transgenic approaches to define the specific role of PECAM-1 and its alternatively spliced isoforms in embryonic vascular ontogeny. To facilitate these studies, the laboratory has developed techniques for adenoviral mediated, tissue specific gene delivery in situ and in utero, during critical stages of cardiovascular development. Most recently, we have identified restricted expression of PECAM-1 to the inner cell mass of the pre-implantation embryo defining the first ICM specific cell adhesion molecule and suggesting a role for PECAM-1 in maintaining stem cell pluripotency. To this end, we have begun characterization of both the ICM and endothelial specific regulatory regions of PECAM-1. In addition, the laboratory has begun analysis of the first endocardial specific transcription factor identified to date, Nuclear Factor of Activated T cells (NFATc1) and has demonstrated that it is required for normal aortic and pulmonary valve formation utilizing null mutations in the mouse. Strategies aimed at defining the "upstream" and "downstream" mechanisms by which NFATc regulates semilunar valve formation include chimeric analysis by ES cell blastocyst complementation, representational display with microarray screening, as well as quantitative anatomical and physiological assessment using high resolution ultrasound and MRI microscopy. Finally, we are developing strategies for endothelial specific gene mutations using the Cre-Lox system and defining inducible endothelial specific promoters to allow temporal a spatial gene manipulation throughout the vascular system. We are particularly interested in delineating the role of the receptor tyrosine kinase, Tie1, in pulmonary vascular development. We have documented that there is a burst of Tie1 expression in the pulmonary vasculature that is associated with rapid lung maturation in the neonatal period and are using whole lung bud culture and postnatal analysis to furhther determine the role Tie1 plays in pulmonary vascular maturation.

Langworthy, M, Zhou, B, de Caestecker, M, Moeckel, G, Baldwin, HS. NFATc1 identifies a population of proximal tubule cell progenitors. J Am Soc Nephrol, 20(2), 311-21, 2009. PMCID:2637056

Misfeldt, A, Boyle, S, Tompkins, KL, Bautch, VL, Labosky, PA, Baldwin, HS. Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors. Dev Biol, , , 2009.

Boyle, S, Misfeldt, A, Chandler, KJ, Deal, KK, Southard-Smith, EM, Mortlock, DP, Baldwin, HS, de Caestecker, M. Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia. Dev Biol, 313(1), 234-45, 2008. PMCID:2699557

Menheniott, TR, Woodfine, K, Schulz, R, Wood, AJ, Monk, D, Giraud, AS, Baldwin, HS, Moore, GE, Oakey, RJ. Genomic imprinting of Dopa decarboxylase in heart and reciprocal allelic expression with neighboring Grb10. Mol Cell Biol, 28(1), 386-96, 2008. PMCID:2223316

Qu, X, Jia, H, Garrity, DM, Tompkins, K, Batts, L, Appel, B, Zhong, TP, Baldwin, HS. Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish. Dev Biol, 317(2), 486-96, 2008.

Song, L, F??ssler, R, Mishina, Y, Jiao, K, Baldwin, HS. Essential functions of Alk3 during AV cushion morphogenesis in mouse embryonic hearts. Dev Biol, 301(1), 276-86, 2007.

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, 55(11), 2974-85, 2006.

Brown, CB, Baldwin, HS. Neural crest contribution to the cardiovascular system. Adv Exp Med Biol, 589, 134-54, 2006.

Chen, JW, Zhou, B, Yu, QC, Shin, SJ, Jiao, K, Schneider, MD, Baldwin, HS, Bergelson, JM. Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves. Circ Res, 98(7), 923-30, 2006.

DeLisser, HM, Helmke, BP, Cao, G, Egan, PM, Taichman, D, Fehrenbach, M, Zaman, A, Cui, Z, Mohan, GS, Baldwin, HS, Davies, PF, Savani, RC. Loss of PECAM-1 function impairs alveolarization. J Biol Chem, 281(13), 8724-31, 2006.

Jiao, K, Langworthy, M, Batts, L, Brown, CB, Moses, HL, Baldwin, HS. Tgfbeta signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development. Development, 133(22), 4585-93, 2006.

Liske, MR, Greeley, CS, Law, DJ, Reich, JD, Morrow, WR, Baldwin, HS, Graham, TP, Strauss, AW, Kavanaugh-McHugh, AL, Walsh, WF, , . Report of the Tennessee Task Force on Screening Newborn Infants for Critical Congenital Heart Disease. Pediatrics, 118(4), e1250-6, 2006.

Allen, HD, Bricker, JT, Freed, MD, Hurwitz, RA, McQuinn, TC, Schieken, RM, Strong, WB, Zahka, KG, Sanders, SP, Colan, SD, Cordes, TM, Donofrio, MT, Ensing, GJ, Geva, T, Kimball, TR, Sahn, DJ, Silverman, NH, Sklansky, MS, Weinberg, PM, Beekman, RH, Hellenbrand, WE, Lloyd, TR, Lock, JE, Mullins, CE, Rome, JJ, Teitel, DF, Vetter, VL, Silka, MJ, Van Hare, GF, Walsh, EP, Kulik, T, Giglia, TM, Kocis, KC, Mahoney, LT, Schwartz, SM, Wernovsky, G, Wessel, DL, Murphy, DJ, Foster, E, Benson, DW, Baldwin, HS, Mahoney, LT, McQuinn, TC, , , , , , . ACC/AHA/AAP recommendations for training in pediatric cardiology. Pediatrics, 116(6), 1574-96, 2005.

Benson, DW, Baldwin, HS, Mahoney, LT, McQuinn, TC, , , , , , . ACCF/AHA/AAP recommendations for training in pediatric cardiology. Task force 7: training guidelines for research in pediatric cardiology. J Am Coll Cardiol, 46(7), 1401-3, 2005.

Briegel, KJ, Baldwin, HS, Epstein, JA, Joyner, AL. Congenital heart disease reminiscent of partial trisomy 2p syndrome in mice transgenic for the transcription factor Lbh. Development, 132(14), 3305-16, 2005.

Frank, DB, Abtahi, A, Yamaguchi, DJ, Manning, S, Shyr, Y, Pozzi, A, Baldwin, HS, Johnson, JE, de Caestecker, MP. Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension. Circ Res, 97(5), 496-504, 2005.

Graham, TP, Beekman, RH, Allen, HD, Bricker, JT, Freed, MD, Hurwitz, RA, McQuinn, TC, Schieken, RM, Strong, WB, Zahka, KG, Sanders, SP, Colan, SD, Cordes, TM, Donofrio, MT, Ensing, GJ, Geva, T, Kimball, TR, Sahn, DJ, Silverman, NH, Sklansky, MS, Weinberg, PM, Hellenbrand, WE, Lloyd, TR, Lock, JE, Mullins, CE, Romes, JJ, Teitel, DF, Vetter, VL, Silka, MJ, Van Hare, GF, Walsh, EP, Kulik, T, Giglia, TM, Kocis, KC, Mahoney, LT, Schwartz, SM, Wernovsky, G, Wessel, DL, Murphy, D, Foster, E, Benson, DW, Baldwin, HS, Hirshfeld, JW, Kugler, JD, Moskowitz, WB, Creager, MA, Lorell, BH, Merli, G, Rodgers, GP, Rutherford, JD, Tracy, CM, Weitz, HH, , , , , , , , . ACCF/AHA/AAP recommendations for training in pediatric cardiology. A report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence (ACC/AHA/AAP Writing Committee to Develop Training Recommendations for Pediatric Cardiology). Circulation, 112(16), 2555-80, 2005.

Zhou, B, Wu, B, Tompkins, KL, Boyer, KL, Grindley, JC, Baldwin, HS. Characterization of Nfatc1 regulation identifies an enhancer required for gene expression that is specific to pro-valve endocardial cells in the developing heart. Development, 132(5), 1137-46, 2005.

Baldwin, HS. Only our patients know for sure. Circ Res, 94(11), 1401-2, 2004.

Phoon, CK, Ji, RP, Aristiz?!bal, O, Worrad, DM, Zhou, B, Baldwin, HS, Turnbull, DH. Embryonic heart failure in NFATc1-/- mice: novel mechanistic insights from in utero ultrasound biomicroscopy. Circ Res, 95(1), 92-9, 2004.

Jiao, K, Kulessa, H, Tompkins, K, Zhou, Y, Batts, L, Baldwin, HS, Hogan, BL. An essential role of Bmp4 in the atrioventricular septation of the mouse heart. Genes Dev, 17(19), 2362-7, 2003. PMCID:218073

Maschhoff, KL, Anziano, PQ, Ward, P, Baldwin, HS. Conservation of Sox4 gene structure and expression during chicken embryogenesis. Gene, 320, 23-30, 2003.

Dees, E, Baldwin, HS. New frontiers in molecular pediatric cardiology. Curr Opin Pediatr, 14(5), 627-33, 2002.

Ismat, FA, Baldwin, HS, Karl, TR, Weinberg, PM. Coronary anatomy in congenitally corrected transposition of the great arteries. Int J Cardiol, 86(2-3), 207-16, 2002.

Jones, PL, Chapados, R, Baldwin, HS, Raff, GW, Vitvitsky, EV, Spray, TL, Gaynor, JW. Altered hemodynamics controls matrix metalloproteinase activity and tenascin-C expression in neonatal pig lung. Am J Physiol Lung Cell Mol Physiol, 282(1), L26-35, 2002.

Loomes, KM, Taichman, DB, Glover, CL, Williams, PT, Markowitz, JE, Piccoli, DA, Baldwin, HS, Oakey, RJ. Characterization of Notch receptor expression in the developing mammalian heart and liver. Am J Med Genet, 112(2), 181-9, 2002.

Taichman, DB, Loomes, KM, Schachtner, SK, Guttentag, S, Vu, C, Williams, P, Oakey, RJ, Baldwin, HS. Notch1 and Jagged1 expression by the developing pulmonary vasculature. Dev Dyn, 225(2), 166-75, 2002.

Zhou, B, Cron, RQ, Wu, B, Genin, A, Wang, Z, Liu, S, Robson, P, Baldwin, HS. Regulation of the murine Nfatc1 gene by NFATc2. J Biol Chem, 277(12), 10704-11, 2002.

Robson, P, Stein, P, Zhou, B, Schultz, RM, Baldwin, HS. Inner cell mass-specific expression of a cell adhesion molecule (PECAM-1/CD31) in the mouse blastocyst. Dev Biol, 234(2), 317-29, 2001.

Badran, S, Schachtner, SK, Baldwin, HS, Rome, JJ. Optimization of adenoviral vector-mediated gene transfer to pulmonary arteries in newborn swine. Hum Gene Ther, 11(8), 1113-21, 2000.

Maschhoff, KL, Baldwin, HS. Molecular determinants of neural crest migration. Am J Med Genet, 97(4), 280-8, 2000.

Mickanin, CS, Baldwin, HS. The application of adenoviral vectors in the study of mammalian cardiovascular development. Methods Mol Biol, 135, 537-43, 2000.

Baldwin, HS. Advances in understanding the molecular regulation of cardiac development. Curr Opin Pediatr, 11(5), 413-8, 1999.

Dandolu, BR, Baldwin, HS, Norwood, WI, Jacobs, ML. Tetralogy of Fallot with anomalous coronary artery: double outflow technique. Ann Thorac Surg, 67(4), 1178-80, 1999.

Loomes, KM, Underkoffler, LA, Morabito, J, Gottlieb, S, Piccoli, DA, Spinner, NB, Baldwin, HS, Oakey, RJ. The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome. Hum Mol Genet, 8(13), 2443-9, 1999.

Baldwin, HS, Artman, M. Recent advances in cardiovascular development: promise for the future. Cardiovasc Res, 40(3), 456-68, 1998.

Leconte, I, Fox, JC, Baldwin, HS, Buck, CA, Swain, JL. Adenoviral-mediated expression of antisense RNA to fibroblast growth factors disrupts murine vascular development. Dev Dyn, 213(4), 421-30, 1998.

Piedboeuf, B, Gamache, M, Frenette, J, Horowitz, S, Baldwin, HS, Petrov, P. Increased endothelial cell expression of platelet-endothelial cell adhesion molecule-1 during hyperoxic lung injury. Am J Respir Cell Mol Biol, 19(4), 543-53, 1998.

Ranger, AM, Grusby, MJ, Hodge, MR, Gravallese, EM, de la Brousse, FC, Hoey, T, Mickanin, C, Baldwin, HS, Glimcher, LH. The transcription factor NF-ATc is essential for cardiac valve formation. Nature, 392(6672), 186-90, 1998.

Srinivasan, S, Baldwin, HS, Aristizabal, O, Kwee, L, Labow, M, Artman, M, Turnbull, DH. Noninvasive, in utero imaging of mouse embryonic heart development with 40-MHz echocardiography. Circulation, 98(9), 912-8, 1998.

Baldwin, HS, Mickanin, C, Buck, C. Adenovirus-mediated gene transfer during initial organogenesis in the mammalian embryo is promoter-dependent and tissue-specific. Gene Ther, 4(11), 1142-9, 1997.

Galili, N, Baldwin, HS, Lund, J, Reeves, R, Gong, W, Wang, Z, Roe, BA, Emanuel, BS, Nayak, S, Mickanin, C, Budarf, MI, Buck, CA. A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region. Genome Res, 7(4), 399, 1997.

Galili, N, Baldwin, HS, Lund, J, Reeves, R, Gong, W, Wang, Z, Roe, BA, Emanuel, BS, Nayak, S, Mickanin, C, Budarf, ML, Buck, CA. A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region. Genome Res, 7(1), 17-26, 1997.

George, EL, Baldwin, HS, Hynes, RO. Fibronectins are essential for heart and blood vessel morphogenesis but are dispensable for initial specification of precursor cells. Blood, 90(8), 3073-81, 1997.

Terry, RW, Kwee, L, Baldwin, HS, Labow, MA. Cre-mediated generation of a VCAM-1 null allele in transgenic mice. Transgenic Res, 6(5), 349-56, 1997.

Baldwin, HS. Early embryonic vascular development. Cardiovasc Res, 31 Spec No, E34-45, 1996.

Buck, CA, Edelman, JM, Buck, CE, Kennedy, G, Baldwin, HS. Expression patterns of adhesion receptors in the developing mouse lung: functional implications. Cell Adhes Commun, 4(2), 69-87, 1996.

Rongish, BJ, Hinchman, G, Doty, MK, Baldwin, HS, Tomanek, RJ. Relationship of the extracellular matrix to coronary neovascularization during development. J Mol Cell Cardiol, 28(10), 2203-15, 1996.

Baldwin, HS. What''s new in cardiology. Pediatr Rev, 16(12), 443-7, 1995.

Fogel, MA, Donofrio, MT, Baldwin, HS, Weinberg, PM. Effect of persistent left superior vena cava on hemodynamic calculations. Am J Cardiol, 76(3), 204-7, 1995.

Kwee, L, Baldwin, HS, Shen, HM, Stewart, CL, Buck, C, Buck, CA, Labow, MA. Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. Development, 121(2), 489-503, 1995.

Suzuki, HR, Solursh, M, Baldwin, HS. Relationship between fibronectin expression during gastrulation and heart formation in the rat embryo. Dev Dyn, 204(3), 259-77, 1995.

Turnbull, DH, Bloomfield, TS, Baldwin, HS, Foster, FS, Joyner, AL. Ultrasound backscatter microscope analysis of early mouse embryonic brain development. Proc Natl Acad Sci U S A, 92(6), 2239-43, 1995. PMCID:42459

Yan, HC, Baldwin, HS, Sun, J, Buck, CA, Albelda, SM, DeLisser, HM. Alternative splicing of a specific cytoplasmic exon alters the binding characteristics of murine platelet/endothelial cell adhesion molecule-1 (PECAM-1). J Biol Chem, 270(40), 23672-80, 1995.

Baldwin, HS, Lloyd, TR, Solursh, M. Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ. Circ Res, 74(2), 244-52, 1994.

Baldwin, HS, Shen, HM, Yan, HC, DeLisser, HM, Chung, A, Mickanin, C, Trask, T, Kirschbaum, NE, Newman, PJ, Albelda, SM. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development. Development, 120(9), 2539-53, 1994.

Buck, CA, Baldwin, HS, DeLisser, H, Mickanin, C, Shen, HM, Kennedy, G, Chen, A, Edelman, JM, Albelda, SM. Cell adhesion receptors and early mammalian heart development: an overview. C R Acad Sci III, 316(9), 838-59, 1993.

Piali, L, Albelda, SM, Baldwin, HS, Hammel, P, Gisler, RH, Imhof, BA. Murine platelet endothelial cell adhesion molecule (PECAM-1)/CD31 modulates beta 2 integrins on lymphokine-activated killer cells. Eur J Immunol, 23(10), 2464-71, 1993.

Bogen, SA, Baldwin, HS, Watkins, SC, Albelda, SM, Abbas, AK. Association of murine CD31 with transmigrating lymphocytes following antigenic stimulation. Am J Pathol, 141(4), 843-54, 1992. PMCID:1886651

Baldwin, HS, Jensen, KL, Solursh, M. Myogenic cytodifferentiation of the precardiac mesoderm in the rat. Differentiation, 47(3), 163-72, 1991.

Lloyd, TR, Baldwin, HS. Emulation of conduction system functions in the hearts of early mammalian embryos. Pediatr Res, 28(5), 425-8, 1990.

Baldwin, HS, Solursh, M. Degradation of hyaluronic acid does not prevent looping of the mammalian heart in situ. Dev Biol, 136(2), 555-9, 1989.

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