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. In collaborative work, we are investigating the mechanisms of adipose tissue fibrosis and remodeling. 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:
• Investigating the mechanisms of how ACLP/AEBP1 mutations cause Ehlers-Danlos syndrome (EDS)
• Defining the the role of ACLP in mechanotransduction pathways that control progenitor differentiation.
• Developing strategies to organ fibrosis through targeting ACLP
• Uncovering new mechanisms that control adipose tissue fibrosis.
- Member of the Molecular Medicine Program, Boston University School of Medicine
- Associate Professor, Biochemistry, Boston University School of Medicine
- Member, BU-BMC Cancer Center, Boston University
- Member, Evans Center for Interdisciplinary Biomedical Research, Boston University
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Graduate Medical Sciences
- Member, Genome Science Institute, Boston University
- Boston University School of Medicine, PhD
- Boston University, BA
- Published on 6/1/2020
Vishwanath N, Monis WJ, Hoffmann GA, Ramachandran B, DiGiacomo V, Wong JY, Smith ML, Layne MD. Mechanisms of aortic carboxypeptidase-like protein secretion and identification of an intracellularly retained variant associated with Ehlers-Danlos syndrome. J Biol Chem. 2020 Jul 10; 295(28):9725-9735. PMID: 32482891.
- Published on 12/7/2018
Lee MJ, Pickering RT, Shibad V, Wu Y, Karastergiou K, Jager M, Layne MD, Fried SK. Impaired Glucocorticoid Suppression of TGFß Signaling in Human Omental Adipose Tissues Limits Adipogenesis and May Promote Fibrosis. Diabetes. 2019 03; 68(3):587-597. PMID: 30530781.
- Published on 7/5/2018
Baron RM, Kwon MY, Castano AP, Ghanta S, Riascos-Bernal DF, Lopez-Guzman S, Macias AA, Ith B, Schissel SL, Lederer JA, Reeves R, Yet SF, Layne MD, Liu X, Perrella MA. Frontline Science: Targeted expression of a dominant-negative high mobility group A1 transgene improves outcome in sepsis. J Leukoc Biol. 2018 10; 104(4):677-689. PMID: 29975792.
- Published on 5/25/2018
Jager M, Lee MJ, Li C, Farmer SR, Fried SK, Layne MD. Aortic carboxypeptidase-like protein enhances adipose tissue stromal progenitor differentiation into myofibroblasts and is upregulated in fibrotic white adipose tissue. PLoS One. 2018; 13(5):e0197777. PMID: 29799877.
- Published on 3/29/2018
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. Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome. Am J Hum Genet. 2018 04 05; 102(4):696-705. PMID: 29606302.
- 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.
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