• Title Instructor
  • Education PhD: Chemical Engineering Carnegie-Mellon
  • Web Address Costello Laboratory
  • Area of Interest Enzymes, kinetics, diffusion-and-reaction models, molecular modeling, molecular dynamics simulation, heparan sulfate (HS) proteoglycans, HS-protein interactions, post-translational modifications

I am interested in the underlying mechanisms and functional consequences of heparan sulfate (HS) proteoglycan interference in various disease pathways, including emphysema, Alzheimer’s disease, and age-related macular degeneration. I am also involved in the identification and characterization of proteins and post-translational modifications (PTMs) related to the progression of these diseases. My quantitative approach to this research is based on a combination of biochemical, biophysical, and computational techniques. As a result of this unique approach, I have made major contributions to defining the mechanism by which HS controls the inflammatory enzyme neutrophil elastase in emphysema. An exciting offshoot of this work has been the development of a novel computational model (ChamP) that predicts the structure of HS chains and identifies the patterns of protein binding. The combination of the ChamP algorithm with in silico methods of molecular modeling and molecular dynamics simulation has become an innovative tool for discerning HS structural elements associated with protein interactions. In addition, my recent mass spectrometry-based work has contributed to the refinement of a software program (STRAP PTM) that uses counting methods for differential analysis of PTM changes which occur with disease. Ultimately, my research will provide a common basis for the creation of new strategies in understanding, detecting, and treating a wide range of diseases.

  1. Spencer JL, Bhatia VN, Whelan SA, Costello CE, McComb ME. STRAP PTM: Software Tool for Rapid Annotation and Differential Comparison of Protein Post-Translational Modifications. Curr Protoc Bioinformatics. 2013 Dec; 44:13.22.1-36. PMID: 25422678.
    View in: PubMed
  2. Nugent MA, Zaia J, Spencer JL. Heparan sulfate-protein binding specificity. Biochemistry (Mosc). 2013 Jul; 78(7):726-35. PMID: 24010836.
    View in: PubMed
  3. Araújo AD, Majumdar A, Parameswaran H, Yi E, Spencer JL, Nugent MA, Suki B. Dynamics of enzymatic digestion of elastic fibers and networks under tension. Proc Natl Acad Sci U S A. 2011 Jun 7; 108(23):9414-9. PMID: 21606336.
    View in: PubMed
  4. Guarnieri F, Spencer JL, Lucey EC, Nugent MA, Stone PJ. A human surfactant peptide-elastase inhibitor construct as a treatment for emphysema. Proc Natl Acad Sci U S A. 2010 Jun 8; 107(23):10661-6. PMID: 20534582.
    View in: PubMed
  5. Spencer JL, Bernanke JA, Buczek-Thomas JA, Nugent MA. A computational approach for deciphering the organization of glycosaminoglycans. PLoS One. 2010; 5(2):e9389. PMID: 20186334.
    View in: PubMed
  6. Nugent MA, Mitsi M, Spencer JL. Proteins and Peptides: Pharmacokinetic, Pharmacodynamic, and Metabolic Outcomes(eds: Mrsny RJ, Daugherty A). In vitro/in vivo correlations of pharmacokinetics, pharmacodynamics, and metabolism for extracellular matrix-binding growth factors. Informa Healthcare. New York. 2009; 53-79.
  7. Spencer JL, Stone PJ, Nugent MA. New insights into the inhibition of human neutrophil elastase by heparin. Biochemistry. 2006 Aug 1; 45(30):9104-20. PMID: 16866356.
    View in: PubMed
  8. Rawls HR, Lentz DL, Cobb GW, Bailey MS, Spencer J, Williams DA, Walley D, Vidra J. Interproximal penetration of commercial toothbrushes as determined by static and dynamic tests using recommended brushing techniques. J Clin Dent. 1993; 4:88-95.
  9. Spencer, JL,Brown, LF. Experimental observations of gas phase-adsorbed phase interactions during counterdiffusion in porous alumina. J Chem Physics. 1975; 63(7):2882-9.

Complete list can be found at BU Profiles

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