Department of Regenerative Medicine and Cell biology

wessels

Andy Wessels , Ph.D.
Professor

Room 648, Basic Science Building
Office: (843) 792-8183
Lab: (843) 792-2316

Email: wesselsa@musc.edu

The Wessels Lab: Full List of Pubs via PubMed
The Wessels Lab: Grant Support
The Wessels Lab: Members

 

Education:

Ing Biochemistry, Ir. W. van den Broek Inst., Amsterdam 1979
MS Chemistry, University of Amsterdam 1987
PhD Anatomy/Embryology, University of Amsterdam 1991

Research Interests:
Each year, nearly twice as many children die in the United States from congenital heart disease (CHD) as from all forms of childhood cancers combined. In the western world, the incidence of CHD varies from 8-10/1000 in the live newborn population. The overall goal of the research performed in the Wessels Laboratory is to unravel the developmental events that are involved in normal cardiac development and to elucidate the mechanisms that lead to congenital heart malformations.  The lab currently focusses on two major research projects related to this theme.

  1. Elucidating the role of the dorsal mesenchymal protrusion (DMP) in the pathogenesis of Atrioventricular Septal Defects (AVSD): The DMP is a structure at the venous pole of the heart that derives from the so-called Second Heart Field (Snarr et al., 2007a,b). In previous studies we have demonstrated that perturbation of DMP development plays a very important role in the pathology of congenital heart malformations, specifically in the etiology of AVSD, a heart defect frequently found in patients with Down Syndrome (Briggs et al., 2012). In this project, we aim to elucidate the molecular pathways that drive normal DMP development and to determine the DMP-associated mechanisms that result in AVSDs.
  2. Establishing the role of epicardially-derived cells (EPDCs) in valvuloseptal development: For many years, the Wessels lab has been investigating the role of the epicardium in heart development (Perez-Pomares et al., 2002, 2003; Wessels and Perez-Pomares, 2004). Using a mouse model that allows the tracing of epicardially-derived cells, we have recently found that EPDCs significantly contribute to the parietal leaflets of the atrioventricular valves. Interestingly, the AV valve leaflets that are associated to the ventricular septum do not contain significant numbers of EPDCs (Wessels et al., 2012). We are currently investigating how this preferential migration of EPDCs into the parietal leaflets is regulated and what the significance of this finding is in relation to congenital and acquired defects of the AV valves.

Approach:

To achieve our goals we use a variety of cell biological techniques, including in vitro tissue culture assays, immunohistochemistry, in situ hybridization, experimental embryology, cell-fate tracing techniques. Many of our studies involve mouse models for congenital heart disease and transgenic mouse technology.

Recent Publications:

  1. Nagalakshmi VK, Lindner V, Wessels A, Yu J.  (2014) microRNA-dependent temporal gene expression in the ureteric bud epithelium during mammalian kidney development. Developmental Dynamics.  Nov 5. doi: 10.1002/dvdy.24221.
  2. Lockhart, M.M., B.J.D. Boukens, A.L. Phelps, C-L. M. Brown, K.A. Toomer, T.A. Burns, R.D. Mukherjee, R.A. Norris, T.C. Trusk, M.J.B. van den Hoff, and A. Wessels (2014) Alk3 mediated Bmp signaling controls the contribution of epicardially-derived cells to the tissues of the atrioventricular junction. Developmental Biology 396 : 8–18.
  3. Lockhart, M.M., A.L. Phelps, M. van den Hoff, and A. Wessels (2014) The Epicardium and the Development of the Atrioventricular Junction. Journal of Developmental Biology 2: 1-17 [PMID: 24926431].
  4. Van den Hoff M.,  A. van Wijk, Q. Gunst, and A. Wessels (2014) Cardiac regeneration from activated epicardium. Cardiovasc Res. 103 Suppl 1:S101 [PMID: 25020293]. 
  5. Briggs LE, Phelps AL, Brown E, Kakarla J, Anderson RH, van den Hoff MJ & Wessels A. Expression of the BMP receptor Alk3 in the second heart field is essential for development of the dorsal mesenchymal protrusion and atrioventricular septation. Circ Res 2013 112: 1420-1432 [PMID: 23584254].
  6. Lockhart MM, Wirrig EE, Phelps AL, Ghatnekar AV, Barth JL, Norris RA & Wessels A. Mef2c regulates transcription of the extracellular matrix protein cartilage link protein 1 in the developing murine heart. PLoS One 2013 8: e57073 [PMID: 23468913].
  7. Sauls K, de Vlaming A, Harris BS, Williams K, Wessels A, Levine RA, Slaugenhaupt SA, Goodwin RL, Pavone LM, Merot J, Schott JJ, Le Tourneau T, Dix T, Jesinkey S, Feng Y, Walsh C, Zhou B, Baldwin S, Markwald RR & Norris RA. Developmental basis for filamin-A-associated myxomatous mitral valve disease. Cardiovasc Res 2012 96: 109-119 [PMID: 22843703].
  8. Briggs LE, Kakarla J & Wessels A. The pathogenesis of atrial and atrioventricular septal defects with special emphasis on the role of the dorsal mesenchymal protrusion. Differentiation 2012 84: 117-130 [PMID: 22709652].
  9. Wessels A, van den Hoff MJ, Adamo RF, Phelps AL, Lockhart MM, Sauls K, Briggs LE, Norris RA, van Wijk B, Perez-Pomares JM, Dettman RW & Burch JB. Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart. Dev Biol 2012 366: 111-124 [PMID: 22546693].
  10. Dupuis LE, McCulloch DR, McGarity JD, Bahan A, Wessels A, Weber D, Diminich AM, Nelson CM, Apte SS & Kern CB. Altered versican cleavage in ADAMTS5 deficient mice; a novel etiology of myxomatous valve disease. Dev Biol 2011 357: 152-164 [PMID: 21749862].
  11. Cortellino S, Xu J, Sannai M, Moore R, Caretti E, Cigliano A, Le Coz M, Devarajan K, Wessels A, Soprano D, Abramowitz LK, Bartolomei MS, Rambow F, Bassi MR, Bruno T, Fanciulli M, Renner C, Klein-Szanto AJ, Matsumoto Y, Kobi D, Davidson I, Alberti C, Larue L & Bellacosa A. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 2011 146: 67-79 [PMID: 21722948].
  12. Lockhart M, Wirrig E, Phelps A & Wessels A. Extracellular matrix and heart development. Birth Defects Res A Clin Mol Teratol 2011 91: 535-550 [PMID: 21618406].
  13. Terada R, Warren S, Lu JT, Chien KR, Wessels A & Kasahara H. Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation. Cardiovasc Res 2011 91: 289-299 [PMID: 21285290].
  14. Norris RA, Moreno-Rodriguez R, Wessels A, Merot J, Bruneval P, Chester AH, Yacoub MH, Hagege A, Slaugenhaupt SA, Aikawa E, Schott JJ, Lardeux A, Harris BS, Williams LK, Richards A, Levine RA & Markwald RR. Expression of the familial cardiac valvular dystrophy gene, filamin-A, during heart morphogenesis. Dev Dyn 2010 239: 2118-2127 [PMID: 20549728].
  15. Anderson RH, Wessels A & Vettukattil JJ. Morphology and morphogenesis of atrioventricular septal defect with common atrioventricular junction. World J Pediatr Congenit Heart Surg 2010 1: 59-67 [PMID: 23804724].
  16. Kern CB, Wessels A, McGarity J, Dixon LJ, Alston E, Argraves WS, Geeting D, Nelson CM, Menick DR & Apte SS. Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies. Matrix Biol 2010 29: 304-316 [PMID: 20096780].
  17. Snarr BS, Kern CB & Wessels A. Origin and fate of cardiac mesenchyme. Dev Dyn 2008 237: 2804-2819 [PMID: 18816864].
  18. Pearson GD, Devereux R, Loeys B, Maslen C, Milewicz D, Pyeritz R, Ramirez F, Rifkin D, Sakai L, Svensson L, Wessels A, Van Eyk J, Dietz HC, National Heart L, Blood I & National Marfan Foundation Working G. Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on research in Marfan syndrome and related disorders. Circulation 2008 118: 785-791 [PMID: 18695204].
  19. Cooley MA, Kern CB, Fresco VM, Wessels A, Thompson RP, McQuinn TC, Twal WO, Mjaatvedt CH, Drake CJ & Argraves WS. Fibulin-1 is required for morphogenesis of neural crest-derived structures. Dev Biol 2008 319: 336-345 [PMID: 18538758].
  20. Snarr BS, O'Neal JL, Chintalapudi MR, Wirrig EE, Phelps AL, Kubalak SW & Wessels A. Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development. Circ Res 2007 101: 971-974 [PMID: 17947796].
  21. Wirrig EE, Snarr BS, Chintalapudi MR, O'Neal J L, Phelps AL, Barth JL, Fresco VM, Kern CB, Mjaatvedt CH, Toole BP, Hoffman S, Trusk TC, Argraves WS & Wessels A. Cartilage link protein 1 (Crtl1), an extracellular matrix component playing an important role in heart development. Dev Biol 2007 310: 291-303 [PMID: 17822691].
  22. Snarr BS, Wirrig EE, Phelps AL, Trusk TC & Wessels A. A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development. Dev Dyn 2007 236: 1287-1294 [PMID: 17265457].
  23. Kruithof BP, van Wijk B, Somi S, Kruithof-de Julio M, Perez Pomares JM, Weesie F, Wessels A, Moorman AF & van den Hoff MJ. BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage. Dev Biol 2006 295: 507-522 [PMID: 16753139].
  24. Sedmera D, Wessels A, Trusk TC, Thompson RP, Hewett KW & Gourdie RG. Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture. Am J Physiol Heart Circ Physiol 2006 291: H1646-1652 [PMID: 16679393].
  25. Moralez I, Phelps A, Riley B, Raines M, Wirrig E, Snarr B, Jin JP, Van Den Hoff M, Hoffman S & Wessels A. Muscularizing tissues in the endocardial cushions of the avian heart are characterized by the expression of h1-calponin. Dev Dyn 2006 235: 1648-1658 [PMID: 16502418].
  26. Shen Y, Leatherbury L, Rosenthal J, Yu Q, Pappas MA, Wessels A, Lucas J, Siegfried B, Chatterjee B, Svenson K & Lo CW. Cardiovascular phenotyping of fetal mice by noninvasive high-frequency ultrasound facilitates recovery of ENU-induced mutations causing congenital cardiac and extracardiac defects. Physiol Genomics 2005 24: 23-36 [PMID: 16174781].
  27. Drake CJ, Wessels A, Trusk T & Little CD. Elevated vascular endothelial cell growth factor affects mesocardial morphogenesis and inhibits normal heart bending. Dev Dyn 2006 235: 10-18 [PMID: 16170779].
  28. Norris RA, Kern CB, Wessels A, Wirrig EE, Markwald RR & Mjaatvedt CH. Detection of betaig-H3, a TGFbeta induced gene, during cardiac development and its complementary pattern with periostin. Anat Embryol (Berl) 2005 210: 13-23 [PMID: 16034610].
  29. Yu H, Wessels A, Tint GS & Patel SB. Partial rescue of neonatal lethality of Dhcr7 null mice by a nestin promoter-driven DHCR7 transgene expression. Brain Res Dev Brain Res 2005 156: 46-60 [PMID: 15862627].
  30. Beon M, Harley RA, Wessels A, Silver RM & Ludwicka-Bradley A. Myofibroblast induction and microvascular alteration in scleroderma lung fibrosis. Clin Exp Rheumatol 2004 22: 733-742 [PMID: 15638048].
  31. Yu Q, Shen Y, Chatterjee B, Siegfried BH, Leatherbury L, Rosenthal J, Lucas JF, Wessels A, Spurney CF, Wu YJ, Kirby ML, Svenson K & Lo CW. ENU induced mutations causing congenital cardiovascular anomalies. Development 2004 131: 6211-6223 [PMID: 15548583].
  32. Norris RA, Kern CB, Wessels A, Moralez EI, Markwald RR & Mjaatvedt CH. Identification and detection of the periostin gene in cardiac development. Anat Rec A Discov Mol Cell Evol Biol 2004 281: 1227-1233 [PMID: 15532025].
  33. Mjaatvedt CH, Klewer S, Wessels A & Gourdie RG. Een geslaagd jubileum! The 10th Weinstein Developmental Cardiovascular Conference in Leiden. Dev Dyn 2004 231: 655-659 [PMID: 15376316].
  34. Adamo RF, Guay CL, Edwards AV, Wessels A & Burch JB. GATA-6 gene enhancer contains nested regulatory modules for primary myocardium and the embedded nascent atrioventricular conduction system. Anat Rec A Discov Mol Cell Evol Biol 2004 280: 1062-1071 [PMID: 15372489].
  35. Yu H, Wessels A, Chen J, Phelps AL, Oatis J, Tint GS & Patel SB. Late gestational lung hypoplasia in a mouse model of the Smith-Lemli-Opitz syndrome. BMC Dev Biol 2004 4: 1 [PMID: 15005800].
  36. Lo CW & Wessels A. Cx43 gap junctions in cardiac development. Trends Cardiovasc Med 1998 8: 264-269 [PMID: 14987562].
  37. Wessels A & Perez-Pomares JM. The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec A Discov Mol Cell Evol Biol 2004 276: 43-57 [PMID: 14699633].
  38. Wessels A & Sedmera D. Developmental anatomy of the heart: a tale of mice and man. Physiol Genomics 2003 15: 165-176 [PMID: 14612588].
  39. Edwards AV, Davis DL, Juraszek AL, Wessels A & Burch JB. Transcriptional regulation in the mouse atrioventricular conduction system. Novartis Found Symp 2003 250: 177-189; discussion 189-193, 276-179 [PMID: 12956330].
  40. Wessels A, Phelps A, Trusk TC, Davis DL, Edwards AV, Burch JB & Juraszek AL. Mouse models for cardiac conduction system development. Novartis Found Symp 2003 250: 44-59; discussion 59-67, 276-279 [PMID: 12956323].
  41. Reckova M, Rosengarten C, deAlmeida A, Stanley CP, Wessels A, Gourdie RG, Thompson RP & Sedmera D. Hemodynamics is a key epigenetic factor in development of the cardiac conduction system. Circ Res 2003 93: 77-85 [PMID: 12775585].
  42. Perez-Pomares JM, Phelps A, Sedmerova M & Wessels A. Epicardial-like cells on the distal arterial end of the cardiac outflow tract do not derive from the proepicardium but are derivatives of the cephalic pericardium. Dev Dyn 2003 227: 56-68 [PMID: 12701099].
  43. Kruithof BP, van den Hoff MJ, Wessels A & Moorman AF. Cardiac muscle cell formation after development of the linear heart tube. Dev Dyn 2003 227: 1-13 [PMID: 12701094].
  44. Perez-Pomares JM, Carmona R, Gonzalez-Iriarte M, Atencia G, Wessels A & Munoz-Chapuli R. Origin of coronary endothelial cells from epicardial mesothelium in avian embryos. Int J Dev Biol 2002 46: 1005-1013 [PMID: 12533024].
  45. Perez-Pomares JM, Phelps A, Sedmerova M, Carmona R, Gonzalez-Iriarte M, Munoz-Chapuli R & Wessels A. Experimental studies on the spatiotemporal expression of WT1 and RALDH2 in the embryonic avian heart: a model for the regulation of myocardial and valvuloseptal development by epicardially derived cells (EPDCs). Dev Biol 2002 247: 307-326 [PMID: 12086469].
  46. Li WE, Waldo K, Linask KL, Chen T, Wessels A, Parmacek MS, Kirby ML & Lo CW. An essential role for connexin43 gap junctions in mouse coronary artery development. Development 2002 129: 2031-2042 [PMID: 11934868].
  47. Cheng G, Wessels A, Gourdie RG & Thompson RP. Spatiotemporal and tissue specific distribution of apoptosis in the developing chick heart. Dev Dyn 2002 223: 119-133 [PMID: 11803575].
  48. van den Hoff MJ, Kruithof BP, Moorman AF, Markwald RR &Wessels A. Formation of myocardium after the initial development of the linear heart tube. Dev Biol 2001 240: 61-76 [PMID: 11784047].
  49. Davis DL, Edwards AV, Juraszek AL, Phelps A, Wessels A & Burch JB. A GATA-6 gene heart-region-specific enhancer provides a novel means to mark and probe a discrete component of the mouse cardiac conduction system. Mech Dev 2001 108: 105-119 [PMID: 11578865].
  50. McQuinn TC, Miga DE, Mjaatvedt CH, Phelps AL & Wessels A. Cardiopulmonary malformations in the inv/inv mouse. Anat Rec 2001 263: 62-71 [PMID: 11331972].
  51. Waller BR, 3rd, McQuinn T, Phelps AL, Markwald RR, Lo CW, Thompson RP & Wessels A. Conotruncal anomalies in the trisomy 16 mouse: an immunohistochemical analysis with emphasis on the involvement of the neural crest. Anat Rec 2000 260: 279-293 [PMID: 11066038].
  52. Wessels A, Anderson RH, Markwald RR, Webb S, Brown NA, Viragh S, Moorman AF & Lamers WH. Atrial development in the human heart: an immunohistochemical study with emphasis on the role of mesenchymal tissues. Anat Rec 2000 259: 288-300 [PMID: 10861362].
  53. Wessels A & Markwald R. Cardiac morphogenesis and dysmorphogenesis. I. Normal development. Methods Mol Biol 2000 136: 239-259 [PMID: 10840715].
  54. Waller BR, 3rd & Wessels A. Cardiac morphogenesis and dysmorphogenesis. An immunohistochemical approach. Methods Mol Biol 2000 135: 151-161 [PMID: 10791312].
  55. Epstein JA, Li J, Lang D, Chen F, Brown CB, Jin F, Lu MM, Thomas M, Liu E, Wessels A & Lo CW. Migration of cardiac neural crest cells in Splotch embryos. Development 2000 127: 1869-1878 [PMID: 10751175].
  56. Bergwerff M, Gittenberger-de Groot AC, Wisse LJ, DeRuiter MC, Wessels A, Martin JF, Olson EN & Kern MJ. Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus. Virchows Arch 2000 436: 12-19 [PMID: 10664157].
  57. Davis DL, Wessels A & Burch JB. An Nkx-dependent enhancer regulates cGATA-6 gene expression during early stages of heart development. Dev Biol 2000 217: 310-322 [PMID: 10625556].
  58. MacNeill C, French R, Evans T, Wessels A & Burch JB. Modular regulation of cGATA-5 gene expression in the developing heart and gut. Dev Biol 2000 217: 62-76 [PMID: 10625536].

 

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