Biomedical Research Education & Training
Faculty Member

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

Email Address:

Baldwin, H. Scott's picture
Academic history
B.A., Univ of Virginia
M.D., Univ of Virginia
, Univ. of Iowa
, Univ. of Rochester/Strong Mem. Hospt.

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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