Matthew A. Nugent
Boston University School of Medicine
Silvio Conte Building, Office: K420; Lab: K421
72 E. Concord Street
Boston, MA 02118
Lab Phone: 617-638-4043
Joint Appointment: Professor of Opthalmology; Professor of Biomedical Engineering
BA, Brandeis University, Waltham, MA
PhD, Brandeis University, Waltham, MA
Postdoctoral Training: Massachusetts Institute of Technology
The research in our laboratory is focused on how growth factors and the extracellular matrix interact to control mammalian cells. In particular, we are focused on how the large class of heparin-binding growth factors are regulated by heparin and heparan sulfate proteoglycans. We apply a combination of biochemical, molecular, biophysical, and computational approaches in conjunction with cell culture and animal studies to generate a systems biology view of growth factor regulation that incorporate the influence of multiple factors on one another. We apply this approach to studies aimed at understanding the details of growth factor-receptor recognition and activation, the regulation of angiogenesis, and the control of extracellular matrix turnover. The overriding theme to our research is to use quantitative methods to analyze complex biological processes in order to develop predictive models of living systems that can be used to probe basic mechanisms and to assist in the rational design of new therapies for human disease. Currently we are focusing on the involvement of these processes in cardiovascular disease and chronic obstructive pulmonary disease.
- Facilitated diffusion of VEGF165 through descemet’s membrane with sucrose octasulfate. Fannon M, Forsten-Williams K, Zhao B, Bach E, Parekh PP, Chu CL, Goerges-Wildt AL, Buczek-Thomas JA, Nugent MA. J Cell Physiol. 2012 Nov;227(11):3693-700. doi: 10.1002/jcp.24077.
- Recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts. Bais MV, Nugent MA, Stephens DN, Sume SS, Kirsch KH, Sonenshein GE, Trackman PC. PLoS One. 2012;7(2):e31188. Epub 2012 Feb 8.
- Complex receptor-ligand dynamics control the response of the VEGF system to protease injury. Forsten-Williams K, Kurtagic E, Nugent MA. BMC Syst Biol. 2011 Oct 21;5:170.
- Cell-cell interactions mediate the response of vascular smooth muscle cells to substrate stiffness. Sazonova OV, Lee KL, Isenberg BC, Rich CB, Nugent MA, Wong JY. Biophys J. 2011 Aug 3;101(3):622-30.
- Dynamics of enzymatic digestion of elastic fibers and networks under tension. Araújo AD, Majumdar A, Parameswaran H, Yi E, Spencer JL, Nugent MA, Suki B. Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9414-9.
- Highly sulfated nonreducing end-derived heparan sulfate domains bind fibroblast growth factor-2 with high affinity and are enriched in biologically active fractions. Naimy H, Buczek-Thomas JA, Nugent MA, Leymarie N, Zaia J. J Biol Chem. 2011 Jun 3;286(22):19311-9.
- Sweet cues: How heparan sulfate modification of fibronectin enables growth factor guided migration of embryonic cells. Symes K, Smith EM, Mitsi M, Nugent MA. Cell Adh Migr. 2010 Oct-Dec;4(4):507-10.
- A human surfactant peptide-elastase inhibitor construct as a treatment for emphysema. Guarnieri F, Spencer JL, Lucey EC, Nugent MA, Stone PJ. Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10661-6.
- A computational approach for deciphering the organization of glycosaminoglycans. Spencer JL, Bernanke JA, Buczek-Thomas JA, Nugent MA. PLoS One. 2010 Feb 23;5(2):e9389.
- Lysyl oxidase propeptide inhibits FGF-2-induced signaling and proliferation of osteoblasts. Vora SR, Palamakumbura AH, Mitsi M, Guo Y, Pischon N, Nugent MA, Trackman PC. J Biol Chem. 2010 Mar 5;285(10):7384-93.
- PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation. Smith EM, Mitsi M, Nugent MA, Symes K. Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21683-8.
- Ritter, M.C., Jesudason, R, Majumdar, A., Stamenovic, D., Buczek-Thomas, J., Stone, P.J., Nugent, M.A., and Suki, B. A zipper network model of the failure mechanics of extracellular matrices. (2009) Proc. Natl. Acad. Sci USA 106, 1081-1086.
- Kurtagic, E., Jedrychowski, M., and Nugent, M.A. Neutrophil elastase cleaves VEGF to generate a VEGF fragment with altered activity. (2009) Am J Physiol Lung Cell Mol Physiol.296, L534-L546
- Mitsi, M. Forsten-Williams, K., and Nugent, M.A. A Catalytic Role for Heparin within the Extracellular Matrix. (2008) J. Biol. Chem. 283, 34796-34807.
- Forsten-Williams, K., Chu, C.L., Fannon, M., Buczek-Thomas, J., and Nugent, M.A. Control of Growth Factor Networks by Heparan Sulfate Proteoglycans. (2008) Ann Biomed Eng 36, 2134-2148.
- Buczek-Thomas, J., Hsia, E., Rich, C.B, Foster, JA, and Nugent, M.A. Inhibition of histone acetyltransferase by heparin and heparan sulfate. (2008) J. Cell. Biochem. 105, 108-120.
- Baker, A.B., Ettenson, D.S., Jonas, M., Nugent, M.A, Iozzo, R.V., and Edelman, E.R. Endothelial Cells Provide Feedback Control for Vascular Remodeling Through a Mechanosensitive Autocrine TGF-ß Signaling Pathway. (2008) Circ. Res. 103, 289-97.
- Yang, S., Nugent, M.A., and Panchenko, M.P., EGF Antagonizes TGF-β Induced Tropoelastin Expression in Lung Fibroblasts via Stabilization of Smad Corepressor TGIF. (2008) Am J Physiol Lung Cell Mol Physiol. 295, L143-51.
- Fannon, M, Forsten-Williams, K, Nugent, MA, Gregory, KJ, Chu, CL, Goerges-Wildt, AL, Panigrahy, D, Kaipainen, A, Lapp, C, Shing, Y. Sucrose Octasulfate Modulates Fibroblast Growth Factor-2 Binding, Transport and Activity: Potential for Regulation of Tumor Growth. (2008) J. Cell. Physiol. 215, 434-441.
- Suki, B., Majumdar, A., Nugent, M.A., and Bates, J.H.T. In silico Modeling of Interstitial Lung Mechanics: Implications for Disease Development and Repair (2007) Drug Discovery Today: Disease Models. 4, 139-145.
- Mitsi, M., Hong, Z., Costello, C.E., and Nugent, M.A. Heparin-mediated conformational changes in fibronectin expose vascular endothelial growth factor binding sites. (2006) Biochemistry 45, 10319-10328.
- Spencer, J., Stone, P.J. and Nugent, M.A. New insights into the inhibition of human neutrophil elastase by heparin. (2006) Biochemistry 45, 9104-9120.
- Dicamillo SJ, Yang S, Panchenko MV, Toselli PA, Naggar EF, Rich CB, Stone PJ, Nugent MA, Panchenko MP. Neutrophil elastase initiated EGFR/MEK/ERK signaling counteracts the stabilizing effect of autocrine TGF-β on tropoelastin mRNA in lung fibroblasts. (2006) Am J Physiol Lung Cell Mol Physiol. 291, L232-243.
- Forsten-Williams, K., Chua, C. C., and Nugent, M. A. (2005) The kinetics of FGF-2 binding to heparan sulfate proteoglycans and MAP kinase signaling, J Theor Biol 233, 483-99.
- Gopalakrishnan, M., Forsten-Williams, K., Nugent, M. A., and Tauber, U. C. (2005) Effects of receptor clustering on ligand dissociation kinetics: theory and simulations, Biophys J 89, 3686-700.
- Chu, CL, Goerges, AL, Nugent, MA. Identification of common and specific growth factor binding sites in heparan sulfate proteoglycans. (2005) Biochemistry 44, 12203-13.
- Buczek-Thomas JA, Lucey EC, Stone PJ, Chu CL, Rich CB, Carreras I, Goldstein RH, Foster JA, Nugent MA. Elastase mediates the release of growth factors from lung in vivo. (2004) Am J Respir Cell Mol Biol. 31:344-50.
- Goerges AL, Nugent MA. pH Regulates Vascular Endothelial Growth Factor Binding to Fibronectin: A Mechanism for control of extracellular storage and release. (2004) J Biol Chem. 279:2307-15.
- Chu CL, Buczek-Thomas JA, Nugent MA. Heparan sulphate proteoglycans modulate fibroblast growth factor-2 binding through a lipid raft-mediated mechanism. (2004) Biochem J. 379:331-41.
- Chua CC, Rahimi N, Forsten-Williams K, Nugent MA. Heparan sulfate proteoglycans function as receptors for fibroblast growth factor-2 activation of extracellular signal-regulated kinases 1 and 2. (2004) Circ Res. 94:316-23.
- Liu J, Rich CB, Buczek-Thomas JA, Nugent MA, Panchenko MP, Foster JA. Heparin-binding EGF-like growth factor regulates elastin and FGF-2 expression in pulmonary fibroblasts. (2003) Am J Physiol Lung Cell Mol Physiol. 285:L1106-15.
- Rich CB, Carreras I, Lucey EC, Jaworski JA, Buczek-Thomas JA, Nugent MA, Stone P, Foster JA. Transcriptional Regulation of Pulmonary Elastin Gene Expression In Elastase-Induced Injury. (2003) Am. J. Physiol Lung Cell Mol. Physiol. 285, L354-62.
- Izvolsky KI, Zhong L, Wei L, Yu Q, Nugent MA, Cardoso WV. Heparan sulfates expressed in the distal lung are required for FGF10 branching to the epithelium and for airway branching. (2003) Am. J. Physiol Lung Cell Mol. Physiol. 285:L838-46.
- Fannon, M., Forsten-Williams, K.E., Dowd, C.J., Freedman, D.A., Folkman, J., and Nugent, M.A. Binding inhibition of angiogenic factors by heparan sulfate proteoglycans in aqueous humor: Potential mechanism for maintainance of an avascular environment. (2003) FASEB J. 17, 902-4.
- Goerges, A.L., and Nugent, M.A. Regulation of vascular endothelial growth factor binding and activity by extracellular pH. (2003) J. Biol. Chem. 278, 19518-25.