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 β (TGFβ) 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)
- Uncovering new mechanisms that control adipose tissue fibrosis
- Defining the the role of ACLP in mechanotransduction pathways that control progenitor differentiation.
Neya Vishwanath – MAMS student
Bhavana Ramachandran – Research technician
Luan Nguyen – undergraduate student
- 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 in press.
- 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. 2018 Dec 07. PMID: 30530781.
- 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.
- 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 Apr 05; 102(4):696-705. PMID: 29606302.
- 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 Jul 05. PMID: 29975792.
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.
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.
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.
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.
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.
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.
Complete list can be found at BU Profiles
GMS BI777 Techniques Biomedical Research
GMS FC762 Critical Thinking in Biomedical Research