Roger Markwald

Roger R. Markwald, Ph.D.
Distinguished University Professor

Director, Cardiovascular Developmental Biology Center

Room 613, Children's Research Institute
Office: (843) 792-5628
Lab: (843) 792-7928

Email: markwald@musc.edu


BS Biology/Chemistry California St. Polytechnic Univ. 1965
MS Anatomy Colorado State University 1968
PhD Anatomy Colorado State University 1969

Research Interests:

My laboratory has pursued studies on the cell and molecular mechanisms of heart development  that utilized in vivo dynamic labeling studies to demonstrate that heart development is progressive, irreversible and occurs by the addition of new segments including ones derived from extracardiac sources.  Three dimensional   culture assays were also  developed that faithfully recapitulated in vivo morphogenetic processes which permitted identification of:  (1) a novel heart forming field that gave origin to the outflow track at the arterial pole of the heart (,  (2)  specific growth factors of the TGFβ supergene as inducers of the outflow track and the transformation of specific populations of endothelial cells into multiple progenitor cells of  internal partitions that divide the heart into right and left sides a and their respective valves and (3) specific   matricellular proteins (periostin and CCN1,2) as ligands that activate integrin-linked,  nodal intracellular kinase pathways in valvuloseptal progenitor cells that promote their differentiation into fibroblasts and regulate cytoskeletal changes that promote their remodeling into sculpted leaflets.  Modifications of the culture system have also permitted the functional assessment of the viscoelastic properties of developing valves and the role of biomechanical signaling in cardiac cell and matrix differentiation. 

Current studies focus on using patient based,  gene discoveries  for developing remedial etiologies and therapies for congenital heart malformations and developmentally-linked,  adult heart valve diseases.   We are also exploring the use of bone marrow derived, hematopoietic stem cells as carriers of genetic “payloads” to normalize or restore the function of degenerative heart valve diseases or to re-engineer  cardiac fibrotic tissues like infarct scars to benefit patient health following cardiac injury.  Lastly, we are applying and integrating  bioprinting technology and principles of  developmental biology to engineer  complex micro-organs for use as personalized tissue replacements or to study mechanisms of  human diseases. Our spheroidal approach to bioprinting tissues is  shown in the figure below.  Spheroids called “bioink” are formulated from stem cells and hydrogels containing inductive signals and linkers  - are robotically positioned and assembled into 3D structures such as the tubular (vascular-like) structure shown. Details of the process are described in a video paper  Grace et al. 2015

Roger Markwald


Selected Recent Publications:

  1. Dina C, Bouatia-Naji N, Tucker N, Delling FN, Toomer K, Durst R, Perrocheau M, Fernandez-Friera L, Solis J; PROMESA investigators, Le Tourneau T, Chen MH, Probst V, Bosse Y, Pibarot P, Zelenika D, Lathrop M, Hercberg S, Roussel R, Benjamin EJ, Bonnet F, Lo SH, Dolmatova E, Simonet F, Lecointe S, Kyndt F, Redon R, Le Marec H, Froguel P, Ellinor PT, Vasan RS, Bruneval P, Markwald RR, Norris RA, Milan DJ, Slaugenhaupt SA, Levine RA, Schott JJ, Hagege AA, Mvp-France, Jeunemaitre X; Leducq Transatlantic MITRAL Network. Genetic association analyses highlight biological pathways underlying mitral valve prolapse. Nat Genet. 2015, Aug 24 PMID: 26301497
  2. Durst R, Sauls K, Peal DS, deVlaming A, Toomer K, Leyne M, Salani M, Talkowski ME, Brand H, Perrocheau M, Simpson C, Jett C, Stone MR, Charles F, Chiang C, Lynch SN, Bouatia-Naji N, Delling FN, Freed LA, Tribouilloy C, Le Tourneau T, LeMarec H, Fernandez-Friera L, Solis J, Trujillano D, Ossowski S, Estivill X, Dina C, Bruneval P, Chester A, Schott JJ, Irvine KD, Mao Y, Wessels A, Motiwala T, Puceat M, Tsukasaki Y, Menick DR, Kasiganesan H, Nie X, Broome AM, Williams K, Johnson A, Markwald RR, Jeunemaitre X, Hagege A, Levine RA, Milan DJ, Norris RA, Slaugenhaupt SA. Mutations in DCHS1 cause mitral valve prolapse. Nature 2015, Aug 10 PMID: 26258302
  3. Misra S, Hascall VC, Markwald RR, Ghatak S. Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer. Front Immunol. 2015, 6:201 PMID: 25999946 PMCID: PMC4422082
  4. Sugi Y, Kern MJ, Markwald RR, Burnside JL. Periostin Expression is Altered in Aortic Valves in Smad6 Mutant Mice. J Neonatal Biol. 2012, Jan 21;1. pii: 4692 PMID: 25383261 PMCID: PMC4224111
  5. Jia J, Richards DJ, Pollard S, Tan Y, Rodriguez J, Visconti RP, Trusk TC, Yost MJ, Yao H, Markwald RR, Mei Y. Engineering alginate as bioink for bioprinting. Acta Biomater. 2014, 10(10):4323-31 PMID: 24998183 PMCID: PMC4350909
  6. Tan Y, Richards DJ, Trusk TC, Visconti RP, Yost MJ, Kindy MS, Drake CJ, Argraves WS, Markwald RR, Mei Y. 3D printing facilitated scaffold-free tissue unit fabrication. Biofabrication. 2014, 6(2):024111 PMID: 24717646 PMCID: PMC4418504
  7. Conway SJ, Izuhara K, Kudo Y, Litvin J, Markwald RR, Ouyang G, Arron JR, Holweg CT, Kudo A, The role of periostin in tissue remodeling across health and disease. Cell Mol Life Sci. 71:1279-88. 2014 PMID: 24146092
  8. Ma Z, Liu Q, Yang H, Runyan RB, Eisenberg CA, Xu M, Borg TK, Markwald R, Wang Y, Gao BZ. Laser patterning for the study of MSC cardiogenic differentiation at the single-cell level. Light Sci Appl. 2013, 2 PMID: 24527266 PMCID: PMC3920285
  9. Ghatak S, Misra S, Norris RA, Moreno-Rodriguez RA, Hoffman S, Levine RA, Hascall VC, Markwald RR. Periostin induces intracellular cross-talk between kinases and hyaluronan in atrioventricular valvulogenesis. J Biol Chem. 2014, Mar 21;289(12):8545-61. PMID: 24469446 PMCID: PMC3961678
  10. Duval D, Lardeux A, Le Tourneau T, Norris RA, Markwald RR, Sauzeau V, Probst V, Le Marec H, Levine R, Schott JJ, Merot J. Valvular dystrophy associated filamin A mutations reveal a new role of its first repeats in small-GTPase regulation. Biochim Biophys Acta. 2014, 1843(2):234-44 PMID: 24200678 PMCID: PMC3928473
  11. Twal WO, Klatt SC, Harikrishnan K, Gerges E, Cooley MA, Trusk TC, Zhou B, Gabr MG, Shazly T, Lessner SM, Markwald RR, Argraves WS. Cellularized microcarriers as adhesive building blocks for fabrication of tubular tissue constructs. Ann Biomed Eng. 2014, 42(7):1470-81 PMID: 23943070 PMCID: PMC3925209
  12. Kolpa HJ, Peal DS, Lynch SN, Giokas AC, Ghatak S, Misra S, Norris RA, Macrae CA, Markwald RR, Ellinor P, Bischoff J, Milan DJ. miR-21 represses Pdcd4 during cardiac valvulogenesis. Development. 2013, May;140(10):2172-80. PMID: 23578931 PMCID: PMC3640220
  13. 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(1):109-19 PMID: 22843703 PMCID: PMC3444235
  14. de Vlaming A, Sauls K, Hajdu Z, Visconti RP, Mehesz AN, Levine RA, Slaugenhaupt SA, Hagège A, Chester AH, Markwald RR, Norris RA. Atrioventricular valve development: new perspectives on an old theme. Differentiation. 2012, 84(1):103-16 PMID: 22579502 PMCID: PMC3389153
  15. Bingruo Wu, Zheng Zhang, Wendy Lui, Xiangjian Chen, Yidong Wang,1 Roger R. Markwald,  Scott Baldwin, Ching-Pin Chang and Bin Zhou/ Endocardial Cells Form Coronary Arteries by Angiogenesis through Myocardial to Endocardial VEGF Signaling.  Cell. 1012, 151(5):1083-96. PMID: 23178125

Complete List of 231 Published Work in MyBibliography: 

Last updated on 29-Oct-2015

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