Department of Regenerative Medicine and Cell biology

Chip Norris

Russell A. Norris, Ph.D.
Assistant Professor


Room 608, Children's Research Institute
Office: (843) 792-1544


Email: norrisra@musc.edu

Education:

University of Cincinnati 1991-1995 Bachelors of Science (Biology)
Medical University of South Carolina 1995-2000 PhD (Molecular, Cellular and Pathobiology)
Medical University of South Carolina 2001-2006 Post Doctoral Research
Medical University of South Carolina 2007-Current Assistant Professor

Research Interests:

A primary focus of the Norris lab is to deal with basic questions in formation of the cardiac valves and pathological processes that result in valve disease. The overall design follows a “cycle of discovery” that begins with the clinical condition, identifies gene candidates, and explores their mechanism of action and susceptibility to rescue. Mechanistic studies in turn point to related pathways for further gene discovery. Through an international consortium of clinicians and scientists, our lab has contributed to identifying new genes that cause valve disease in humans. Our ongoing projects have defined that these genes play a crucial role during the development of the valves, essentially laying the blueprint for valve construction. Thus, we propose that inherited heart valve disease is caused by inborn errors in the development of this structure. By studying these disease genes we can gain an understanding for how the valve develops and why valve defects occur. Harnessed with this information, targeted therapeutics can be developed that may be of benefit to patients with valvular heart disease, thus allowing us to complete the “cycle of discovery”.

MVP figure

Recent Publications:

  1. Kolpa, H. J., D. S. Peal, S. N. Lynch, A. C. Giokas, S. Ghatak, S. Misra, R. A. Norris, C. A. Macrae, R. R. Markwald, P. Ellinor, J. Bischoff and D. J. Milan. "Mir-21 Represses Pdcd4 During Cardiac Valvulogenesis." Development 140, no. 10 (2013): 2172-80 [PMID: 23578931]
  2. Lockhart, M. M., E. E. Wirrig, A. L. Phelps, A. V. Ghatnekar, J. L. Barth, R. A. Norris and A. Wessels. "Mef2c Regulates Transcription of the Extracellular Matrix Protein Cartilage Link Protein 1 in the Developing Murine Heart." PLoS One 8, no. 2 (2013): e57073 [PMID: 23468913]
  3. Pavone, L. M. and R. A. Norris. "Distinct Signaling Pathways Activated by "Extracellular" and "Intracellular" Serotonin in Heart Valve Development and Disease." Cell Biochem Biophys, (2013) [PMID: 23605455]
  4. Wagner, J. M., R. A. Norris, L. R. Van Dillen, F. P. Thomas and R. T. Naismith. "Four Square Step Test in Ambulant Persons with Multiple Sclerosis: Validity, Reliability, and Responsiveness." Int J Rehabil Res 36, no. 3 (2013): 253-9 [PMID: 23511117]
  5. de Vlaming, A., K. Sauls, Z. Hajdu, R. P. Visconti, A. N. Mehesz, R. A. Levine, S. A. Slaugenhaupt, A. Hagege, A. H. Chester, R. R. Markwald and R. A. Norris. "Atrioventricular Valve Development: New Perspectives on an Old Theme." Differentiation 84, no. 1 (2012): 103-16 [PMID: 22579502]
  6. Doyle, A. J., J. J. Doyle, S. L. Bessling, S. Maragh, M. E. Lindsay, D. Schepers, E. Gillis, G. Mortier, T. Homfray, K. Sauls, R. A. Norris, N. D. Huso, D. Leahy, D. W. Mohr, M. J. Caulfield, A. F. Scott, A. Destree, R. C. Hennekam, P. H. Arn, C. J. Curry, L. Van Laer, A. S. McCallion, B. L. Loeys and H. C. Dietz. "Mutations in the Tgf-Beta Repressor Ski Cause Shprintzen-Goldberg Syndrome with Aortic Aneurysm." Nat Genet 44, no. 11 (2012): 1249-54 [PMID: 23023332]
  7. Sauls, K., A. de Vlaming, B. S. Harris, K. Williams, A. Wessels, R. A. Levine, S. A. Slaugenhaupt, R. L. Goodwin, L. M. Pavone, J. Merot, J. J. Schott, T. Le Tourneau, T. Dix, S. Jesinkey, Y. Feng, C. Walsh, B. Zhou, S. Baldwin, R. R. Markwald and R. A. Norris. "Developmental Basis for Filamin-a-Associated Myxomatous Mitral Valve Disease." Cardiovasc Res 96, no. 1 (2012): 109-19 [PMID: 22843703]
  8. Wessels, A., M. J. van den Hoff, R. F. Adamo, A. L. Phelps, M. M. Lockhart, K. Sauls, L. E. Briggs, R. A. Norris, B. van Wijk, J. M. Perez-Pomares, R. W. Dettman and J. B. Burch. "Epicardially Derived Fibroblasts Preferentially Contribute to the Parietal Leaflets of the Atrioventricular Valves in the Murine Heart." Dev Biol 366, no. 2 (2012): 111-24 [PMID: 22546693]
  9. Gruber, H. E., R. A. Norris, M. J. Kern, G. L. Hoelscher, J. A. Ingram, N. Zinchenko and E. N. Hanley, Jr. "Periostin Is Expressed by Cells of the Human and Sand Rat Intervertebral Discs." Biotech Histochem 86, no. 3 (2011): 199-206 [PMID: 20370359]
  10. Tan, H., L. Junor, R. L. Price, R. A. Norris, J. D. Potts and R. L. Goodwin. "Expression and Deposition of Fibrous Extracellular Matrix Proteins in Cardiac Valves During Chick Development." Microsc Microanal 17, no. 1 (2011): 91-100 [PMID: 21205426]
  11. Chiu, Y. N., R. A. Norris, G. Mahler, A. Recknagel and J. T. Butcher. "Transforming Growth Factor Beta, Bone Morphogenetic Protein, and Vascular Endothelial Growth Factor Mediate Phenotype Maturation and Tissue Remodeling by Embryonic Valve Progenitor Cells: Relevance for Heart Valve Tissue Engineering." Tissue Eng Part A 16, no. 11 (2010): 3375-83 [PMID: 20629541]
  12. Hajdu, Z., V. Mironov, A. N. Mehesz, R. A. Norris, R. R. Markwald and R. P. Visconti. "Tissue Spheroid Fusion-Based in Vitro Screening Assays for Analysis of Tissue Maturation." J Tissue Eng Regen Med 4, no. 8 (2010): 659-64 [PMID: 20603872]
  13. Li, G., R. Jin, R. A. Norris, L. Zhang, S. Yu, F. Wu, R. R. Markwald, A. Nanda, S. J. Conway, S. S. Smyth and D. N. Granger. "Periostin Mediates Vascular Smooth Muscle Cell Migration through the Integrins Alphavbeta3 and Alphavbeta5 and Focal Adhesion Kinase (Fak) Pathway." Atherosclerosis 208, no. 2 (2010): 358-65 [PMID: 19695571]
  14. Markwald, R. R., R. A. Norris, R. Moreno-Rodriguez and R. A. Levine. "Developmental Basis of Adult Cardiovascular Diseases: Valvular Heart Diseases." Ann N Y Acad Sci 1188, (2010): 177-83 [PMID: 20201901]
  15. Norris, R. A., R. Moreno-Rodriguez, A. Wessels, J. Merot, P. Bruneval, A. H. Chester, M. H. Yacoub, A. Hagege, S. A. Slaugenhaupt, E. Aikawa, J. J. Schott, A. Lardeux, B. S. Harris, L. K. Williams, A. Richards, R. A. Levine and R. R. Markwald. "Expression of the Familial Cardiac Valvular Dystrophy Gene, Filamin-a, During Heart Morphogenesis." Dev Dyn 239, no. 7 (2010): 2118-27 [PMID: 20549728]
  16. Teekakirikul, P., S. Eminaga, O. Toka, R. Alcalai, L. Wang, H. Wakimoto, M. Nayor, T. Konno, J. M. Gorham, C. M. Wolf, J. B. Kim, J. P. Schmitt, J. D. Molkentin, R. A. Norris, A. M. Tager, S. R. Hoffman, R. R. Markwald, C. E. Seidman and J. G. Seidman. "Cardiac Fibrosis in Mice with Hypertrophic Cardiomyopathy Is Mediated by Non-Myocyte Proliferation and Requires Tgf-Beta." J Clin Invest 120, no. 10 (2010): 3520-9 [PMID: 20811150]
  17. Norris, R. A., R. Moreno-Rodriguez, S. Hoffman and R. R. Markwald. "The Many Facets of the Matricelluar Protein Periostin During Cardiac Development, Remodeling, and Pathophysiology." J Cell Commun Signal 3, no. 3-4 (2009): 275-86 [PMID: 19798597]
  18. Norris, R. A., J. D. Potts, M. J. Yost, L. Junor, T. Brooks, H. Tan, S. Hoffman, M. M. Hart, M. J. Kern, B. Damon, R. R. Markwald and R. L. Goodwin. "Periostin Promotes a Fibroblastic Lineage Pathway in Atrioventricular Valve Progenitor Cells." Dev Dyn 238, no. 5 (2009): 1052-63 [PMID: 19334280]
  19. Norris RA, Borg TK, Butcher JT, Markwald RR. Neonatal and Adult Cardiovascular Pathophysiological Remodeling and Repair: Developmental Role of Periostin. Ann N Y Acad Sci. 2008 Mar;1123:30-40
  20. Inai, K., Norris R. A., Hoffman, S., Markwald, R. R. and Sugi, Y. BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis. Dev Biol. 2008 Mar 15;315(2):383-96. Epub 2007 Dec 31.
  21. Norris, R.A., Moreno-Rodriguez, R.A., Sugi, Y, Hoffman, S., Amos, J., Hart, M.H., Potts, J., Goodwin, R.L., Markwald, R.R. Periostin Regulates Atrioventricular Valve Maturation. Dev Biol. 2008 Apr 15;316(2):200-13. Epub 2008 Jan 17.
  22. Norris RA, Potts JD, Yost MJ, Junor L, Brooks T, Tan H, Hoffman S, Hart MM, Kern MJ, Damon B, Markwald RR, Goodwin RL Periostin Promotes A Fibroblastic Lineage Pathway In Atrioventricular Valve Progenitor Cells. Dev Dyn. 2009 May;238(5):1052-63.
  23. Li G, Jin R, Norris RA, Zhang L, Yu S, Wu F, Markwald RR, Nanda A, Conway SJ, Smyth SS, Granger DN Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway. Atherosclerosis. 2010 Feb;208(2):358-65.
  24. Norris RA, Moreno-Rodriguez R, Hoffman S, Markwald RR. The Many Facets of the Matricelluar Protein, Periostin During Cardiac Development, Remodeling, And Pathophysiology J Cell Commun Signal. 2009 Dec;3(3-4):275-86.
  25. Markwald RR, Norris RA, Moreno-Rodriguez R, Levine RA. Developmental Basis Of Adult
    Cardiovascular Diseases:  Valvular Heart Diseases. Ann N Y Acad Sci. 2010 Feb;1188:177-83.
  26. Robert A. Levine, Sue Slaugenhaupt, Albert Hagege, Xavier Jeunemaitre, Russell A. Norris, Roger R. Markwald, on behalf of the Leducq Mitral Consortium. Mitral Valve Prolapse: From Genes To New Therapies. The Exciting Potential of an International Network of Scientists and Clinicians.  Society for MVP Syndrome and on-line at www.mitralvalveprolapse.com (Nov 2009).
  27. Norris RA, Moreno-Rodriguez, R, Wessels, A, Merot, J, Hagege, A, Slaugenhaupt, S, Schott, JJ, 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 Jul;239(7):2118-2726.
  28. Chiu, Y-N, Norris RA, Mahler G, Recknagel A, Butcher JT. Complementary and Redundant Roles for TGFβ, BMP, and VEGF in Embryonic Atrioventricular Remodeling: Natural Template for Heart Valve Tissue Engineering. Tissue Eng Part A. 2010 Nov;16(11):3375-83. Epub 2010 Jul 14.
  29. Teekakirikul P, Eminaga S, Toka O, Alcalai R, Wang L, Wakimoto H, Nayor M, Konno T, Gorham JM, Wolf CM, Kim JB, Schmitt JP, Molkentin JD, Norris RA, Tager AM, Hoffman SR, Markwald RR, Seidman CE, Seidman JG. Cardiac fibrosis, in hypertrophic cardiomyopathy, is mediated by non-myocyte proliferation and requires TGFβ. J. Clin Invest. 2010 Sep 1. pii: 42028. doi: 10.1172/JCI42028.
  30. Tan H, Junor L, Price RL, Norris RA, Potts JD, Goodwin RL. Expression and deposition of fibrous extracellular matrix proteins in cardiac valves during chick development. Microsc Microanal. 2011 Feb;17(1):91-100.
  31. 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 Jun 15;366(2):111-24. Epub 2012 Apr 24
  32. de Vlaming A, Sauls K, Hajdu Z, Visconti RP, Mehesz AN, Levine RA, Slaugenhaupt SA, Hagge A, Chester AH, Markwald RR, Norris RA. Atrioventricular valve development: new perspectives on an old theme.  Differentiation. 2012 Jul;84(1):103-16. Epub 2012 May 11.
  33. 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 Oct 1;96(1):109-19. Epub 2012 Jul 25.
  34. Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, Gillis E, Mortier G, Homfray T, Sauls K, Norris RA, Huso ND, Leahy D, Mohr DW, Caulfield MJ, Scott AF, Destre A, Hennekam RC, Arn PH, Curry CJ, Van Laer L, McCallion AS, Loeys BL, Dietz HC. Mutations in the TGF- repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm.  Nat Genet. 2012 Sep 30. doi: 10.1038/ng.2421. [Epub ahead of print]

 

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