The primary goal of our laboratory is to identify novel pathways that control extracellular matrix(ECM) synthesis and assembly as they relate to fibroproliferative and connective tissue diseases. Our long term goal is to use this knowledge to develop therapeutic strategies for these conditions. Fibroproliferative responses are similar to wound healing processes involving accumulation of contractile myofibroblasts and ECM secretion and assembly. Because organ fibrosis, cardiovascular, metabolic/obesity, and cancer pathologies are now recognized to be impacted by fibroblast-myofibroblast differentiation and ECM remodeling our research is examining novel pathways and control mechanisms in these diseases. Central to our studies is determining the function of Aortic Carboxypeptidase-Like Protein (ACLP), a secreted, collagen-binding protein that enhances fibrosis and myofibroblast differentiation through mechanisms that involve stimulating the transforming growth factor ß (TGFß) receptor signaling complex and controlling mechanical signaling and ECM remodeling. Recent work is uncovering the role of ACLP (and AEBP1 genetic mutations in the connective tissue disease Ehlers Danlos Syndrome. There are several active projects in the lab including:
• Defining the the role of ACLP in mechanotransduction pathways that control progenitor differentiation.
• Investigating the mechanisms of how ACLP/AEBP1 mutations cause Ehlers Danlos Syndrome (EDS)
• Developing strategies to organ fibrosis through targeting ACLP
• Studying the stromal reaction in breast cancer.
• Uncovering new mechanisms that control adipose tissue fibrosis.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Member of the Cell and Molecular Biology Program, Boston University School of Medicine
- Member of the Molecular Medicine Program, Boston University School of Medicine
- Boston University School of Medicine, PhD
- Boston University, BA
- Published on 2/20/2018
Blackburn PR, Xu Z, Tumelty KE, Zhao RW, Monis WJ, Harris KG, Gass JM, Cousin MA, Boczek NJ, Mitkov MV, Cappel MA, Francomano CA, Parisi JE, Klee EW, Faqeih E, Alkuraya FS, Layne MD, McDonnell NB, Atwal PS. Biallelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome. Am J Human Genetics, in press. 2018.
- Published on 5/8/2015
Shiwen X, Stratton R, Nikitorowicz-Buniak J, Ahmed-Abdi B, Ponticos M, Denton C, Abraham D, Takahashi A, Suki B, Layne MD, Lafyatis R, Smith BD. A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis. PLoS One. 2015; 10(5):e0126015. PMID: 25955164.
- Published on 1/8/2015
McDonald ME, Li C, Bian H, Smith BD, Layne MD, Farmer SR. Myocardin-related transcription factor A regulates conversion of progenitors to beige adipocytes. Cell. 2015 Jan 15; 160(1-2):105-18. PMID: 25579684.
- Published on 12/20/2014
Xu YX, Ashline D, Liu L, Tassa C, Shaw SY, Ravid K, Layne MD, Reinhold V, Robbins PW. The glycosylation-dependent interaction of perlecan core protein with LDL: implications for atherosclerosis. J Lipid Res. 2015 Feb; 56(2):266-76. PMID: 25528754.
- Published on 11/1/2014
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. PMID: 25034893.
- Published on 3/28/2014
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; 12:22. PMID: 24674138.
- Published on 12/16/2013
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. PMID: 24344132.
- Published on 8/23/2013
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. PMID: 23975851.
- Published on 1/1/2013
Tumelty KE, Layne MD. 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.
- Published on 6/20/2012
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. PMID: 22718766.
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