The primary goal of our laboratory is to identify 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 regulated by fibroblast-myofibroblast differentiation and ECM remodeling our research is examining 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 Ehlers Danlos Syndrome and in aortic aneurysm. There are several active projects in the lab including:
- Defining the the role of ACLP in mechanotransduction pathways that control vascular integrity and aortic aneurysm
- Investigating the mechanisms of how ACLP/AEBP1 mutations cause Ehlers Danlos Syndrome (EDS)
- Uncovering new mechanisms that control adipose tissue fibrosis
Sidrah Ahmed —MAMS student
Isha Havale —undergraduate BME
Amber Liu – undergraduate Biology, summer UROP award
- Dance YW, Meshulam T, Seibel AJ, Obenreder MC, Layne MD, Nelson CM, Tien J. Adipose Stroma Accelerates the Invasion and Escape of Human Breast Cancer Cells from an Engineered Microtumor. Cell and Mol Bioengineer. in press 2021.
- Wang D, Rabhi N, Yet SF, Farmer SR, Layne MD. Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A. Sci Reports 2021 Feb 17; 11:3948.
- Hekman RM, Hume AJ, Goel RK, Abo KM, Huang J, Blum BC, Werder RB, Suder EL, Paul I, Phanse S, Youssef A, Alysandratos KD, Padhorny D, Ojha S, Mora-Martin A, Kretov D, Ash PEA, Verma M, Zhao J, Patten JJ, Villacorta-Martin C, Bolzan D, Perea-Resa C, Bullitt E, Hinds A, Tilston-Lunel A, Varelas X, Farhangmehr S, Braunschweig U, Kwan JH, McComb M, Basu A, Saeed M, Perissi V, Burks EJ, Layne MD, Connor JH, Davey R, Cheng JX, Wolozin BL, Blencowe BJ, Wuchty S, Lyons SM, Kozakov D, Cifuentes D, Blower M, Kotton DN, Wilson AA, Mühlberger E, Emili A. Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2. Mol Cell. 2020 12 17; 80(6):1104-1122.e9. PMID: 33259812
- Jiang WC, Chen CM, Hamdin CD, Orekhov AN, Sobenin IA, Layne MD, Yet SF. Therapeutic Potential of Heme Oxygenase-1 in Aneurysmal Diseases. Antioxidants (Basel). 2020 Nov 19; 9(11). PMID: 33228202
- Zeng C, Motta-Ribeiro GC, Hinoshita T, Lessa MA, Winkler T, Grogg K, Kingston NM, Hutchinson JN, Sholl LM, Fang X, Varelas X, Layne MD, Baron RM, Vidal Melo MF. Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep. Anesthesiology. 2020 11 01; 133(5):1060-1076.. PMID: 32796202
- 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 07 10; 295(28):9725-9735. PMID: 32482891
- 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.
- 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
- 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
- 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
Complete list can be found at BU Profiles
GMS BI777 Techniques Biomedical Research
GMS FC762 Critical Thinking in Biomedical Research