Ing Biochemistry, Ir. W. van den Broek Inst., Amsterdam 1979
MS Chemistry, University of Amsterdam 1987
PhD Anatomy/Embryology, University of Amsterdam 1991
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.
- 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.
- 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.
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.
- Lockhart, M.M., A.L. Phelps, and A. Wessels (2013) The Epicardium and the Development of the Atrioventricular Junction. Journal of Developmental Biology (in press)
- Briggs L.E, Phelps A.L., Brown E., Kakarla J., Anderson R.H., van den Hoff M. J. B., and A. Wessels (2013) Expression of the BMP Receptor Alk3 in the Second Heart Field is Essential for Development of the Dorsal Mesenchymal Protrusion and Atrioventricular Septation. Circulation Research 112:1420-1432.
- Lockhart, M.M., E.E. Wirrig, A.L. Phelps, A.V. Ghatnekar, J.L. Barth, R.A, Norris, and A. Wessels (2013) Mef2c regulates transcription of the extracellular matrix protein Cartilage Link Protein 1 in the developing murine heart. PLoS One. 2013;8(2):e57073. doi: 10.1371/journal.pone.0057073. Epub 2013 Feb 26.
- Sauls K, de Vlaming A, Harris BS, Williams K, Wessels A, Levine RA, Slaugenhaupt SA, Goodwin RL, Pavone L, Merot J, Schott JJ, Le Tourneau T, Dix T, Jesinkey S, Feng Y, Walsh C, Zhou B, Baldwin S, Markwald RR, Norris RA. (2012) Developmental Basis for Filamin-A Associated Myxomatous Mitral Valve Disease. Cardiovasc Res. 2012 Jul 25. [Epub ahead of print]
- Wessels, A, M. J. B. van den Hoff, R. Adamo, M. M. Lockhart, K. Sauls, L.E. Briggs, A.L. Phelps, B. van Wijk, J. M. Perez-Pomares, R. W. Dettman, and John B. E. Burch (2012) Epicardially-derived Fibroblasts and their Contribution to the Developing Heart with Emphasis on their Differential Contribution to the Respective Leaflets of the Atrioventricular Valves Developmental Biology 15;366(2):111-24
- Briggs L.E., J. Kakarla, A. Wessels (2012) The Pathogenesis of Atrial and Atrioventricular Septal Defects with Special Emphasis on the Dorsal Mesenchymal Protrusion. Differentiation 84(1):117- 130.
- Cole-Jeffrey C.T., R.Terada, M. Neth, A.Wessels, H. Kasahara (2012) Progressive anatomical closure of foramen ovale in normal neonatal mouse hearts. The Anatomical Record 295(5):764-8
- Cortellino S., J. Xu, M. Sannai, R. Moore, E. Caretti, A. Cigliano, M. Le Coz, K. Devarajan, A. Wessels, D. Soprano, L. K. Abramowitz, M. S. Bartolomei, F. Rambow, M. Rosaria Bassi, T. Bruno, M. Fanciulli, C. Renner, A. J. Klein-Szanto, Y. Matsumoto, D. Kobi, I. Davidson, C. Alberti, L. Larue, and A. Bellacossa (2011) Thymine DNA Glycosylase is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair. Cell 146(1):67-79.
- Dupuis L.E, D.R McCulloch, J. D. McGarity, A. Bahan, D. Weber, A.M. Diminich, A. Wessels, C. M. Nelson, S. S. Apte, and C.B. Kern (2011) Altered Versican Cleavage in ADAMTS5 Deficient Mice; A Novel Etiology of Myxomatous Valve Disease. Developmental Biology 357(1):152-64.
- Lockhart M., E. Wirrig, A. Phelps and A. Wessels (2011) Extracellular Matrix and Heart Development. Birth Defects Research (Part A) 91:535-550.
- Terada R., S. Warren, J.T. Lu, K.R. Chien, A. Wessels, and H. Kasahara (2011) Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation. Cardiovasc Res. 91(2):289-99.
- Anderson R.H., A. Wessels and J. J. Vettukattil (2010) Morphology and Morphogenesis of Atrioventricular Septal Defect With Common Atrioventricular Junction. World Journal for Pediatric and Congenital Heart Surgery 1:59-67.
- Norris RA, Moreno-Rodriguez R, Wessels A, Merot J, Bruneval P, Chester AH, Yacoub MH, Hagège A, Slaugenhaupt SA, Aikawa E, Schott JJ, Lardeux A, Harris BS, Williams LK, Richards A, Levine RA, Markwald RR. (2010) Expression of the familial cardiac valvular dystrophy gene, filamin-A, during heart morphogenesis.Â Developmental Dynamics 239:2118-2127.
- Kern CB, Wessels A, McGarity J, Dixon LJ, Alston E, Argraves WS, Geeting D, Nelson CM, Menick DR, Apte SS (2010) Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies Matrix Biology 29:304-316.
- Snarr B.S., C.B. Kern, and A. Wessels (2008). Origin and Fate of cardiac Mesenchyme Developmental Dynamics 237:2804-2819.
- Cooley M.A., C.B. Kern, V.M. Fresco, A. Wessels, R.P. Thompson, T.C. McQuinn, W.O. Twal, C.H. Mjaatvedt, C.J. Drake and W.S. Argraves (2008) Fibulin-1 is required for morphogenesis of neural crest-derived structures Developmental Biology 319:336-345.
- Pearson, G, R. Devereux, B. Loeys, C. Maslen, D. Milewicz, R. Pyeritz, F. Ramirez, D. Rifkin, L. Sakai, L. Svensson, A. Wessels, J. Van Eyk, and H. Dietz (2008) Â Report of the National Heart, Lung and Blood Institute and National Marfan Foundation Working Group on Research in Marfan Syndrome and Related Disorders Circulation 118:785-791.
- Snarr B.S., J.L. Oâ€™Neal, Mastan R. Chintalapudi, E.E. Wirrig, A.L. Phelps, S. Kubalak, and A. Wessels (2007).Â Isl1 Expression an the Venous Pole Identifies a Novel Role for the Secondary Heart Field in Cardiac Development Circulation Research 101:971-974.
- Wirrig E.E., B.S. Snarr, Mastan R. Chintalapudi, J.L. O'Neal, A. Phelps, J.L. Barth, V.M. Fresco, C.B. Kern, Corey H Mjaatvedt, B.P. Toole, S. Hoffman, T.C. Trusk, W.S. Argraves, and A. Wessels (2007). Cartilage Link Protein 1 (Crtl1), an extracellular matrix component playing an important role in cardiac development. Developmental Biology310:291-303.
- Snarr, Brian S., Elaine E. Wirrig, Aimee L. Phelps, Thomas C. Trusk, and Andy Wessels (2007) A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development. Developmental Dynamics 236:1287-1294 (with cover).
- Sedmera D., A. Wessels, T.C. Trusk, R.P. Thompson, K.W. Hewett, and R.G. Gourdie (2006) Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture. American Journal of Physiology Heart Circ Physiol 291(4):H1646-52.
- Kruithof B.P.T., B. van Wijk, S. Somi, M. Kruithof-de Julio, F. Weesie, J.-M. PÃ©rez Pomares, A. Wessels, A.F.M. Moorman, and M.J.B. van den Hoff (2006) BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage. Developmental Biology 295(2): 507-522.
- Moralez, I., A. Phelps, B. Riley, M. Raines, E. Wirrig, B. Snarr, J.-P. Jin, M. vd Hoff, S. Hoffman, and A. Wessels (2006) Muscularizing tissues in the endocardial cushions of the avian heart are characterized by the expression of h1-calponin. Developmental Dynamics 235(6):1648-1658.
- Drake, C.J., A. Wessels, T. Trusk, and C.D. LittleÂ (2006) Elevated VEGF affects mesocardial morphogenesis and inhibits normal heart bending. Developmental Dynamics 253:10-18.
- Shen Y., L. Leatherbury, J. Rosenthal, Q. Yu, M.A. Pappas, A.Wessels, B. Siegfried, B. Chatterjee, Karen Svenson, and C.W. Lo (2005) Cardiovascular phenotyping of fetal mice by noninvasive ultrasound and recovery of ENU induced mutations causing congenital cardiac and extracardiac defects. Physiological Genomics 24:23-36.
- Norris R.A., C.B. Kern, A. Wessels, E.I. Wirrig, R. R. Markwald, and C. H. Mjaatvedt (2005) Detection of BigH3, a TGFbeta induced gene, during cardiac development and its complementary pattern with periostin. Anatomy and Embryology 210:13-23.
- Yu H., A. Wessels, G.S. Tint, and S.B. Patel (2005) Partial rescue of neonatal lethality of Dhcr7 null mice by a nestin promoter-driven DHCR7 transgene expression. Brain Res Dev Brain Res 156(1):46-60.
- Wessels A. , A.L. Juraszek, A.V. Edwards, and J. B.E. Burch (2005) The Development of the Cardiac Conduction System: An old story with new perspectives. In: Cardiovascular Development and Congenital Malformations: Molecular and Genetic Mechanisms. Blackwell Publishing, Malden, MA, M. Artman, D.W. Benson, D. Srivastava, M. Nakazawa (eds.), pp. 101-104.
- van den Hoff M.J.B., B.P.T. Kruithof, A. Wessels, R.R. Markwald, A.F.M. Moorman (2005) Regulation of myocardium formation after the initial development of the linear heart tube. In: Cardiovascular Development and Congenital Malformations: Molecular and Genetic Mechanisms. Blackwell Publishing, Malden, MA, M. Artman, D.W. Benson, D. Srivastava, M. Nakazawa (eds.), pp. 37-40.
- Yu Q., Y. Shen, B. Chatterjee, B.H. Siegfried, L. Leatherbury, J. Rosenthal, J.F. Lucas, A. Wessels, C.F. Spurney, Y.J. Wu, M.L. Kirby, K. Svenson, and C. W. Lo (2004) ENU induced mutations causing congenital cardiovascular anomalies. Development 131:6211-6223.
- Norris R.A., C.B. Kern, A.Wessels, E.I. Moralez, R.R. Markwald, C.H. Mjaatvedt (2004) Identification and detection of the periostin gene in cardiac development. Anatomical Record 281A:1227-1233.
- Wessels A., and Perez-Pomares J.M. (2004) The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells.Anatomical Record 276A(1):43-57.
- Adamo, R.F., C.L. Guay, A.V. Edwards, D.L. Davis, A.Wessels and J.B.E. Burch (2004) Overlapping regions of a GATA-6 gene enhancer direct transgene expression either broadly in primitive myocardium or more specifically in the atrioventricular conduction system. Anatomical Record Part A 280A:1062-1071.
- Wessels, A., and D. Sedmera (2003) Developmental Anatomy of the Heart: a tale of mice and man. Physiological Genomics 15: 165-176.
- Pérez-Pomares J.M., A. Phelps, M. Sedmerova, and A. Wessels (2003) 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 Developmental Dynamics 227:56-68
- Kruithof B.P.T., M.J.B. van den Hoff, A. Wessels, and A.F.M. Moorman (2003) Cardiac muscle cell formation after formation of the linear heart tube. Developmental Dynamics 227:1-13.
- Pérez-Pomares J.M., A. Phelps, M. Sedmerova, and A. Wessels (2003) 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 Developmental Dynamics 227:56-68.
- Perez-Pomares, J.M., A. Phelps, M. Sedmerova, R. Carmona, M. González-Iriarte, R. Muñoz-Chápuli, and A. Wessels (2002) 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). Developmental Biology 247:307-326.
- Li, W.E.I., K. Waldo, K.L. Linask, T.Chen, A. Wessels, M.S. Parmacek, M.L. Kirby, and C.W. Lo (2002) An essential role for connexin43 gap juntions in mouse coronary artery development. Development 129:2031-2042.
- Cheng G., A. Wessels, R.G. Gourdie, and R.P. Thompson (2002) The spatiotemporal and tissue-specific distribution of apoptosis in the developing chick heart. Developmental Dynamics 223:119-133.
- Davis, D.L., A.V. Edwards, A.L. Juraszek, A.L. Phelps, A Wessels, and J.E. Burch. (2001) A GATA-6 gene heart-region specific enhancer provides a novel means to mark and probe a discrete component of the mouse cardiac conduction. Mechanisms of Development 108:105-119.
- Van den Hoff, M.J.B., B.P.T. Kruithof, A.F.M. Moorman, R.R. Markwald, and A. Wessels (2001) Formation of myocardium after the initial development of the linear heart tube. Developmental Biology 240:61-76.
- McQuinn, T.D., Miga, C.H., Mjaatvedt, A., and A. Wessels (2001) Cardiopulmonary malformations in the inv/inv mouse. The Anatomical Record 263:62-71.
- Waller III, B.R., T. McQuinn, A.L. Phelps, R.R. Markwald, C.W. Lo, R.P. Thompson and A. Wessels (2000) Conotruncal anomalies in the trisomy 16 mouse: an immunohistochemical analysis with emphasis on the development of the neural crest. The Anatomical Record 260:279-29.
- A. Wessels, R.H. Anderson, R.R. Markwald, S. Webb, N.A. Brown, Sz. Viragh, A.F.M. Moorman and W. H. Lamers (2000) Atrial development in the human heart: an immunohistochemical study with emphasis on the role of menchymal tissues. The Anatomical Record 259:288-300.
- Epstein J.A., J. Li, D. Lang, F. Chen, C.B. Brown, F. Jin, M.M. Liu, M. Thomas, E.-C. J. Liu,A. Wessels, and C.W. Lo (2000) Migration of cardiac neural crest cells in Splotch embryos. Development 127:1869-1878.
- MacNeill, C., R. French, A. Wessels, and J.B.E. Burch. Modular regulation of cGATA5 gene expression in the developing heart and gut. (2000). Developmental Biology 217:62-76.
- Davis D.L., A. Wessels, and J.B.E. Burch (2000) An Nkx-dependent enhancer regulates cGATA-6 gene expression during early stages of heart development. Developmental Biology 217:310-322.