Keywords
Last Name

Matthew D. Layne, PhD

TitleAssistant Professor
InstitutionBoston University School of Medicine
DepartmentBiochemistry
Address72 E. Concord St Silvio Conte (K)
Boston MA 02118
Phone(617) 638-4361
ORCID ORCID Icon0000-0003-0007-4870
Other Positions
TitleGraduate Faculty (Primary Mentor of Grad Students)
InstitutionBoston University School of Medicine, Graduate Medical Sciences

TitleMember of the Cell and Molecular Biology Program
InstitutionBoston University School of Medicine

TitleMember of the Molecular Medicine Program
InstitutionBoston University School of Medicine

 Awards and Honors

Start-EndDescription
2011Fellow of the American Heart Association
 Research Expertise & Professional Interests
Our long-term goals are to understand the transcriptional control of genes, which are upregulated in the vascular smooth muscle cells and fibroblasts in cardiovascular and pulmonary disease. We have identified a secreted protein, aortic carboxypeptidase-like protein (ACLP), which contains a collagen-binding discoidin and a catalytically inactive metallocarboxypeptidase domain. ACLP is expressed in vascular smooth muscle cells and is induced in the diseased blood vessel in vivo. We are defining the mechanisms by which ACLP regulates VSMC proliferation and function using in vitro assays and vascular disease models with transgenic and knockout mice. The lab is also investigating the control of myofibroblast gene expression in pulmonary fibrosis. We are exploring the mechanisms of gene expression and differentiation mechanisms in myofibroblasts and have identified novel signaling pathways and regulatory pathways that may coordinate the expression and subsequent deposition of extracellular matrix proteins in wounded VSMC and fibroblasts.

Current Projects Include:

1. Investigating the regulation of genes in vascular smooth muscle cells in response to injury
2. Determining the role of aortic carboxypeptidase-like protein in vascular smooth muscle biology
3. Defining mechanism of fibroblast/myofibroblast transitions in fibrotic disease

 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Chen CH, Ho HH, Wu ML, Layne MD, Yet SF. Modulation of cysteine-rich protein 2 expression in vascular injury and atherosclerosis. Mol Biol Rep. 2014 Nov; 41(11):7033-41.
    View in: PubMed
  2. Wu ML, Chen CH, Lin YT, Jheng YJ, Ho YC, Yang LT, Chen L, Layne MD, Yet SF. Divergent signaling pathways cooperatively regulate TGFß induction of cysteine-rich protein 2 in vascular smooth muscle cells. Cell Commun Signal. 2014; 12(1):22.
    View in: PubMed
  3. Tumelty KE, Smith BD, Nugent MA, Layne MD. Aortic Carboxypeptidase-like Protein (ACLP) Enhances Lung Myofibroblast Differentiation through Transforming Growth Factor ß Receptor-dependent and -independent Pathways. J Biol Chem. 2014 Jan 31; 289(5):2526-36.
    View in: PubMed
  4. Chen CH, Ho YC, Ho HH, Chang IC, Kirsch KH, Chuang YJ, Layne MD, Yet SF. Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration. Cardiovasc Res. 2013 Dec 1; 100(3):461-71.
    View in: PubMed
  5. Tumelty, K. E. Layne, M. D. Handbook of Proteolytic Enzymes (Rawlings, N. D. and Salvesen, G. S., ed.). Adipocyte Enhancer Binding Protein 1 and Aortic Carboxypeptidase-Like Protein. Academic Press. Oxford. 2013; 1348-1353.
  6. Wang D, Prakash J, Nguyen P, Davis-Dusenbery BN, Hill NS, Layne MD, Hata A, Lagna G. Bone morphogenetic protein signaling in vascular disease: anti-inflammatory action through myocardin-related transcription factor A. J Biol Chem. 2012 Aug 10; 287(33):28067-77.
    View in: PubMed
  7. Wu ML, Layne MD, Yet SF. Heme oxygenase-1 in environmental toxin-induced lung disease. Toxicol Mech Methods. 2012 Jun; 22(5):323-9.
    View in: PubMed
  8. Zhou X, Baron RM, Hardin M, Cho MH, Zielinski J, Hawrylkiewicz I, Sliwinski P, Hersh CP, Mancini JD, Lu K, Thibault D, Donahue AL, Klanderman BJ, Rosner B, Raby BA, Lu Q, Geldart AM, Layne MD, Perrella MA, Weiss ST, Choi AM, Silverman EK. Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP. Hum Mol Genet. 2012 Mar 15; 21(6):1325-35.
    View in: PubMed
  9. Luchsinger LL, Patenaude CA, Smith BD, Layne MD. Myocardin-related transcription factor-A complexes activate type I collagen expression in lung fibroblasts. J Biol Chem. 2011 Dec 23; 286(51):44116-25.
    View in: PubMed
  10. Davis-Dusenbery BN, Chan MC, Reno KE, Weisman AS, Layne MD, Lagna G, Hata A. down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4. J Biol Chem. 2011 Aug 12; 286(32):28097-110.
    View in: PubMed
  11. Danzer E, Layne MD, Auber F, Shegu S, Kreiger P, Radu A, Volpe M, Adzick NS, Flake AW. Gastroschisis in mice lacking aortic carboxypeptidase-like protein is associated with a defect in neuromuscular development of the eviscerated intestine. Pediatr Res. 2010 Jul; 68(1):23-8.
    View in: PubMed
  12. Baron RM, Lopez-Guzman S, Riascos DF, Macias AA, Layne MD, Cheng G, Harris C, Chung SW, Reeves R, von Andrian UH, Perrella MA. Distamycin A inhibits HMGA1-binding to the P-selectin promoter and attenuates lung and liver inflammation during murine endotoxemia. PLoS One. 2010; 5(5):e10656.
    View in: PubMed
  13. Chen CH, Wu ML, Lee YC, Layne MD, Yet SF. Intronic CArG box regulates cysteine-rich protein 2 expression in the adult but not in developing vasculature. Arterioscler Thromb Vasc Biol. 2010 Apr; 30(4):835-42.
    View in: PubMed
  14. Grant MA, Baron RM, Macias AA, Layne MD, Perrella MA, Rigby AC. Netropsin improves survival from endotoxaemia by disrupting HMGA1 binding to the NOS2 promoter. Biochem J. 2009 Feb 15; 418(1):103-12.
    View in: PubMed
  15. Schissel SL, Dunsmore SE, Liu X, Shine RW, Perrella MA, Layne MD. Aortic carboxypeptidase-like protein is expressed in fibrotic human lung and its absence protects against bleomycin-induced lung fibrosis. Am J Pathol. 2009 Mar; 174(3):818-28.
    View in: PubMed
  16. Liu X, Ramjiganesh T, Chen YH, Chung SW, Hall SR, Schissel SL, Padera RF, Liao R, Ackerman KG, Kajstura J, Leri A, Anversa P, Yet SF, Layne MD, Perrella MA. Disruption of striated preferentially expressed gene locus leads to dilated cardiomyopathy in mice. Circulation. 2009 Jan 20; 119(2):261-8.
    View in: PubMed
  17. Lin DW, Chang IC, Tseng A, Wu ML, Chen CH, Patenaude CA, Layne MD, Yet SF. Transforming growth factor beta up-regulates cysteine-rich protein 2 in vascular smooth muscle cells via activating transcription factor 2. J Biol Chem. 2008 May 30; 283(22):15003-14.
    View in: PubMed
  18. Takamiya R, Baron RM, Yet SF, Layne MD, Perrella MA. High mobility group A1 protein mediates human nitric oxide synthase 2 gene expression. FEBS Lett. 2008 Mar 5; 582(5):810-4.
    View in: PubMed
  19. Zurakowski H, Gagnon A, Landry A, Layne MD, Sorisky A. Discoidin domain receptor 2 impairs insulin-stimulated insulin receptor substrate-1 tyrosine phosphorylation and glucose uptake in 3T3-L1 adipocytes. Horm Metab Res. 2007 Aug; 39(8):575-81.
    View in: PubMed
  20. Schissel SL, Layne MD. Telomerase, myofibroblasts, and pulmonary fibrosis. Am J Respir Cell Mol Biol. 2006 May; 34(5):520-2.
    View in: PubMed
  21. Chung SW, Chen YH, Yet SF, Layne MD, Perrella MA. Endotoxin-induced down-regulation of Elk-3 facilitates heme oxygenase-1 induction in macrophages. J Immunol. 2006 Feb 15; 176(4):2414-20.
    View in: PubMed
  22. Wei J, Gorman TE, Liu X, Ith B, Tseng A, Chen Z, Simon DI, Layne MD, Yet SF. Increased neointima formation in cysteine-rich protein 2-deficient mice in response to vascular injury. Circ Res. 2005 Dec 9; 97(12):1323-31.
    View in: PubMed
  23. Gagnon A, Landry A, Proulx J, Layne MD, Sorisky A. Aortic carboxypeptidase-like protein is regulated by transforming growth factor beta in 3T3-L1 preadipocytes. Exp Cell Res. 2005 Aug 15; 308(2):265-72.
    View in: PubMed
  24. Liu X, Wei J, Peng DH, Layne MD, Yet SF. Absence of heme oxygenase-1 exacerbates myocardial ischemia/reperfusion injury in diabetic mice. Diabetes. 2005 Mar; 54(3):778-84.
    View in: PubMed
  25. Ith B, Wei J, Yet SF, Perrella MA, Layne MD. Aortic carboxypeptidase-like protein is expressed in collagen-rich tissues during mouse embryonic development. Gene Expr Patterns. 2005 Apr; 5(4):533-7.
    View in: PubMed
  26. Baron RM, Carvajal IM, Liu X, Okabe RO, Fredenburgh LE, Macias AA, Chen YH, Ejima K, Layne MD, Perrella MA. Reduction of nitric oxide synthase 2 expression by distamycin A improves survival from endotoxemia. J Immunol. 2004 Sep 15; 173(6):4147-53.
    View in: PubMed
  27. Agrawal RS, Muangman S, Layne MD, Melo L, Perrella MA, Lee RT, Zhang L, Lopez-Ilasaca M, Dzau VJ. Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival. Gene Ther. 2004 Jun; 11(12):962-9.
    View in: PubMed
  28. Chen YH, Layne MD, Chung SW, Ejima K, Baron RM, Yet SF, Perrella MA. Elk-3 is a transcriptional repressor of nitric-oxide synthase 2. J Biol Chem. 2003 Oct 10; 278(41):39572-7.
    View in: PubMed
  29. Yet SF, Layne MD, Liu X, Chen YH, Ith B, Sibinga NE, Perrella MA. Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling. FASEB J. 2003 Sep; 17(12):1759-61.
    View in: PubMed
  30. Chang YF, Wei J, Liu X, Chen YH, Layne MD, Yet SF. Identification of a CArG-independent region of the cysteine-rich protein 2 promoter that directs expression in the developing vasculature. Am J Physiol Heart Circ Physiol. 2003 Oct; 285(4):H1675-83.
    View in: PubMed
  31. Ejima K, Layne MD, Carvajal IM, Kritek PA, Baron RM, Chen YH, Vom Saal J, Levy BD, Yet SF, Perrella MA. Cyclooxygenase-2-deficient mice are resistant to endotoxin-induced inflammation and death. FASEB J. 2003 Jul; 17(10):1325-7.
    View in: PubMed
  32. Watanabe M, Layne MD, Hsieh CM, Maemura K, Gray S, Lee ME, Jain MK. Regulation of smooth muscle cell differentiation by AT-rich interaction domain transcription factors Mrf2alpha and Mrf2beta. Circ Res. 2002 Sep 6; 91(5):382-9.
    View in: PubMed
  33. Ejima K, Layne MD, Carvajal IM, Nanri H, Ith B, Yet SF, Perrella MA. Modulation of the thioredoxin system during inflammatory responses and its effect on heme oxygenase-1 expression. Antioxid Redox Signal. 2002 Aug; 4(4):569-75.
    View in: PubMed
  34. Gagnon A, Abaiian KJ, Crapper T, Layne MD, Sorisky A. Down-regulation of aortic carboxypeptidase-like protein during the early phase of 3T3-L1 adipogenesis. Endocrinology. 2002 Jul; 143(7):2478-85.
    View in: PubMed
  35. Storm van's Gravesande K, Layne MD, Ye Q, Le L, Baron RM, Perrella MA, Santambrogio L, Silverman ES, Riese RJ. IFN regulatory factor-1 regulates IFN-gamma-dependent cathepsin S expression. J Immunol. 2002 May 1; 168(9):4488-94.
    View in: PubMed
  36. Layne MD, Yet SF, Maemura K, Hsieh CM, Liu X, Ith B, Lee ME, Perrella MA. Characterization of the mouse aortic carboxypeptidase-like protein promoter reveals activity in differentiated and dedifferentiated vascular smooth muscle cells. Circ Res. 2002 Apr 5; 90(6):728-36.
    View in: PubMed
  37. Melo LG, Agrawal R, Zhang L, Rezvani M, Mangi AA, Ehsan A, Griese DP, Dell'Acqua G, Mann MJ, Oyama J, Yet SF, Layne MD, Perrella MA, Dzau VJ. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation. 2002 Feb 5; 105(5):602-7.
    View in: PubMed
  38. Yet SF, Melo LG, Layne MD, Perrella MA. Heme oxygenase 1 in regulation of inflammation and oxidative damage. Methods Enzymol. 2002; 353:163-76.
    View in: PubMed
  39. Maemura K, Layne MD, Watanabe M, Perrell MA, Nagai R, Lee ME. Molecular mechanisms of morning onset of myocardial infarction. Ann N Y Acad Sci. 2001 Dec; 947:398-402.
    View in: PubMed
  40. Chen YH, Layne MD, Watanabe M, Yet SF, Perrella MA. Upstream stimulatory factors regulate aortic preferentially expressed gene-1 expression in vascular smooth muscle cells. J Biol Chem. 2001 Dec 14; 276(50):47658-63.
    View in: PubMed
  41. Layne MD, Patel A, Chen YH, Rebel VI, Carvajal IM, Pellacani A, Ith B, Zhao D, Schreiber BM, Yet SF, Lee ME, Storch J, Perrella MA. Role of macrophage-expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice. FASEB J. 2001 Dec; 15(14):2733-5.
    View in: PubMed
  42. Layne MD, Yet SF, Maemura K, Hsieh CM, Bernfield M, Perrella MA, Lee ME. Impaired abdominal wall development and deficient wound healing in mice lacking aortic carboxypeptidase-like protein. Mol Cell Biol. 2001 Aug; 21(15):5256-61.
    View in: PubMed
  43. Perrella MA, Pellacani A, Layne MD, Patel A, Zhao D, Schreiber BM, Storch J, Feinberg MW, Hsieh CM, Haber E, Lee ME. Absence of adipocyte fatty acid binding protein prevents the development of accelerated atherosclerosis in hypercholesterolemic mice. FASEB J. 2001 Aug; 15(10):1774-6.
    View in: PubMed
  44. Yet SF, Tian R, Layne MD, Wang ZY, Maemura K, Solovyeva M, Ith B, Melo LG, Zhang L, Ingwall JS, Dzau VJ, Lee ME, Perrella MA. Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res. 2001 Jul 20; 89(2):168-73.
    View in: PubMed
  45. Wiesel P, Patel AP, Carvajal IM, Wang ZY, Pellacani A, Maemura K, DiFonzo N, Rennke HG, Layne MD, Yet SF, Lee ME, Perrella MA. Exacerbation of chronic renovascular hypertension and acute renal failure in heme oxygenase-1-deficient mice. Circ Res. 2001 May 25; 88(10):1088-94.
    View in: PubMed
  46. Fukumoto S, Hsieh CM, Maemura K, Layne MD, Yet SF, Lee KH, Matsui T, Rosenzweig A, Taylor WG, Rubin JS, Perrella MA, Lee ME. Akt participation in the Wnt signaling pathway through Dishevelled. J Biol Chem. 2001 May 18; 276(20):17479-83.
    View in: PubMed
  47. Sun J, Kamei CN, Layne MD, Jain MK, Liao JK, Lee ME, Chin MT. Regulation of myogenic terminal differentiation by the hairy-related transcription factor CHF2. J Biol Chem. 2001 May 25; 276(21):18591-6.
    View in: PubMed
  48. Maemura K, de la Monte SM, Chin MT, Layne MD, Hsieh CM, Yet SF, Perrella MA, Lee ME. CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression. J Biol Chem. 2000 Nov 24; 275(47):36847-51.
    View in: PubMed
  49. Hsieh CM, Fukumoto S, Layne MD, Maemura K, Charles H, Patel A, Perrella MA, Lee ME. Striated muscle preferentially expressed genes alpha and beta are two serine/threonine protein kinases derived from the same gene as the aortic preferentially expressed gene-1. J Biol Chem. 2000 Nov 24; 275(47):36966-73.
    View in: PubMed
  50. Wiesel P, Foster LC, Pellacani A, Layne MD, Hsieh CM, Huggins GS, Strauss P, Yet SF, Perrella MA. Thioredoxin facilitates the induction of heme oxygenase-1 in response to inflammatory mediators. J Biol Chem. 2000 Aug 11; 275(32):24840-6.
    View in: PubMed
  51. Chin MT, Maemura K, Fukumoto S, Jain MK, Layne MD, Watanabe M, Hsieh CM, Lee ME. Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. J Biol Chem. 2000 Mar 3; 275(9):6381-7.
    View in: PubMed
  52. Maemura K, Hsieh CM, Jain MK, Fukumoto S, Layne MD, Liu Y, Kourembanas S, Yet SF, Perrella MA, Lee ME. Generation of a dominant-negative mutant of endothelial PAS domain protein 1 by deletion of a potent C-terminal transactivation domain. J Biol Chem. 1999 Oct 29; 274(44):31565-70.
    View in: PubMed
  53. Layne MD, Farmer SR. Tumor necrosis factor-alpha and basic fibroblast growth factor differentially inhibit the insulin-like growth factor-I induced expression of myogenin in C2C12 myoblasts. Exp Cell Res. 1999 May 25; 249(1):177-87.
    View in: PubMed
  54. Hsieh CM, Yet SF, Layne MD, Watanabe M, Hong AM, Perrella MA, Lee ME. Genomic cloning and promoter analysis of aortic preferentially expressed gene-1. Identification of a vascular smooth muscle-specific promoter mediated by an E box motif. J Biol Chem. 1999 May 14; 274(20):14344-51.
    View in: PubMed
  55. Yet SF, Perrella MA, Layne MD, Hsieh CM, Maemura K, Kobzik L, Wiesel P, Christou H, Kourembanas S, Lee ME. Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice. J Clin Invest. 1999 Apr; 103(8):R23-9.
    View in: PubMed
  56. Jain MK, Kashiki S, Hsieh CM, Layne MD, Yet SF, Sibinga NE, Chin MT, Feinberg MW, Woo I, Maas RL, Haber E, Lee ME. Embryonic expression suggests an important role for CRP2/SmLIM in the developing cardiovascular system. Circ Res. 1998 Nov 16; 83(10):980-5.
    View in: PubMed
  57. Layne MD, Endege WO, Jain MK, Yet SF, Hsieh CM, Chin MT, Perrella MA, Blanar MA, Haber E, Lee ME. Aortic carboxypeptidase-like protein, a novel protein with discoidin and carboxypeptidase-like domains, is up-regulated during vascular smooth muscle cell differentiation. J Biol Chem. 1998 Jun 19; 273(25):15654-60.
    View in: PubMed
  58. Yet SF, Folta SC, Jain MK, Hsieh CM, Maemura K, Layne MD, Zhang D, Marria PB, Yoshizumi M, Chin MT, Perrella MA, Lee ME. Molecular cloning, characterization, and promoter analysis of the mouse Crp2/SmLim gene. Preferential expression of its promoter in the vascular smooth muscle cells of transgenic mice. J Biol Chem. 1998 Apr 24; 273(17):10530-7.
    View in: PubMed
  59. Jain MK, Layne MD, Watanabe M, Chin MT, Feinberg MW, Sibinga NE, Hsieh CM, Yet SF, Stemple DL, Lee ME. In vitro system for differentiating pluripotent neural crest cells into smooth muscle cells. J Biol Chem. 1998 Mar 13; 273(11):5993-6.
    View in: PubMed
  60. Yet SF, McA'Nulty MM, Folta SC, Yen HW, Yoshizumi M, Hsieh CM, Layne MD, Chin MT, Wang H, Perrella MA, Jain MK, Lee ME. Human EZF, a Krüppel-like zinc finger protein, is expressed in vascular endothelial cells and contains transcriptional activation and repression domains. J Biol Chem. 1998 Jan 9; 273(2):1026-31.
    View in: PubMed
  61. Layne MD. Regulation of myogenin expression and function during myoblast proliferation and differentiation [PhD dissertation]. Boston, MA. 1997.
  62. Zoeller RA, Layne MD, Modest EJ. Animal cell mutants unable to take up biologically active glycerophospholipids. J Lipid Res. 1995 Sep; 36(9):1866-75.
    View in: PubMed
  63. Schreiber BM, Layne MD, Modest EJ. Superoxide production by macrophages stimulated in vivo with synthetic ether lipids. Lipids. 1994 Apr; 29(4):237-42.
    View in: PubMed
  64. Morris-Natschke SL, Gumus F, Marasco CJ, Meyer KL, Marx M, Piantadosi C, Layne MD, Modest EJ. Synthesis of phosphocholine and quaternary amine ether lipids and evaluation of in vitro antineoplastic activity. J Med Chem. 1993 Jul 9; 36(14):2018-25.
    View in: PubMed
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