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.
- Assistant Dean for Research, Boston University Chobanian & Avedisian 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 Chobanian & Avedisian School of Medicine, Graduate Medical Sciences
- Member of the Molecular Medicine Program, Boston University Chobanian & Avedisian School of Medicine
- Member, Genome Science Institute, Boston University
- Boston University School of Medicine, PhD
- Boston University, BA
- Published on 4/12/2022
Chen CH, Ho HH, Jiang WC, Ao-Ieong WS, Wang J, Orekhov AN, Sobenin IA, Layne MD, Yet SF. Cysteine-rich protein 2 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation in mice. J Biomed Sci. 2022 Apr 12; 29(1):25. PMID: 35414069.
- Published on 2/18/2022
Rabhi N, Desevin K, Belkina AC, Tilston-Lunel A, Varelas X, Layne MD, Farmer SR. Obesity-induced senescent macrophages activate a fibrotic transcriptional program in adipocyte progenitors. Life Sci Alliance. 2022 05; 5(5). PMID: 35181634.
- Published on 2/2/2022
Downs M, Sethi MK, Raghunathan R, Layne MD, Zaia J. Matrisome changes in Parkinson's disease. Anal Bioanal Chem. 2022 Apr; 414(9):3005-3015. PMID: 35112150.
- Published on 8/24/2021
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 Mol Bioeng. 2022 Feb; 15(1):15-29. PMID: 35096184.
- Published on 2/17/2021
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 Rep. 2021 02 17; 11(1):3948. PMID: 33597582.
- Published on 1/7/2021
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. 2021 Jan 07; 81(1):212. PMID: 33417854.
- Published on 11/19/2020
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.
- Published on 11/19/2020
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.
- Published on 11/1/2020
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.
- 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 07 10; 295(28):9725-9735. PMID: 32482891.
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