Elizabeth M. Topp

Photo
Professor
Phone:
765-496-7760
Fax:
765-494-6545
E-mail:
Specialization: Protein Stability and Formulation

Education

BChE, 1979, The University of Delaware
ME, 1984, The University of Pennsylvania
PhD, 1986, The University of Michigan

Research

Professor Topp's research focuses on the chemical and physical stability of protein drugs, with particular emphasis on chemical degradation reactions in the amorphous solid state. Currently active research projects address (i) the effects of secondary structure in deamidation in the Fc portion of an IgG, (ii) the development of hydrogen/deuterium exchange methods for examining protein structure and excipient interactions in amorphous solids,(iii) the controlled release of immunomodulating peptides from PLGA matrices in type-1 diabetes, and (iv) mechanisms of degradation of phenylephrine and cetirizine in the solid state.

Topp Lab 4/2015
Topp Lab members, Spring 2015 (back, l to r): Ruichao Xie, Ehab Moussa, Balakrishnan Moorthy, Jainik Panchal, Liz Topp, Reham Nour. (front, L to r): Lavanya Iyer, Yuan Chen, Eunbi Cho, Hamed Ghomi, Saradha Chandrasekhar, Anshul Mishra

Lab Members

Karthik Balakrishna-Chandrababu (Post-Doctoral Research Associate with Dr. Elizabeth Topp)
Lia Bersin (Graduate Student with Dr. Elizabeth Topp)
Yuan Chen (Graduate Student)
Eunbi (Iris) Cho (Graduate Student)
Rajashekar Kammari (Graduate Student)
Harshil K. Renawala (Graduate Student)
Rishabh Tukra (Graduate Student with Dr. Elizabeth Topp)

Representative Publications

http://www.ncbi.nlm.nih.gov/pubmed/?term=topp%2C+elizabeth+m

A cooperative folding unit as the structural link for energetic coupling within a protein. N. W. Gardner, S. M. McGinness, J. Panchal, E. M. Topp and C. Park. Biochemistry, 56/50: 6555-6564, 2017. DOI: 10.1021/acs.biochem.7b00850.

Solid-state hydrogen deuterium exchange mass spectrometry: Correlation of deuterium uptake and long-term stability of lyophilized monoclonal antibody formulations. S. M. Balakrishnan, I. D. Zarraga, L. Kumar, B. Walters, P. Goldbach, E. M. Topp and A. Allmendinger. Molecular Pharmaceutics, 15/1: 1-11, 2018. DOI: 10.1021/acs.molpharmaceut.7b00504. Web publication date: November 28, 2017.

Hydrogen exchange mass spectrometry for proteins adsorbed to solid surfaces, in frozen solutions and in amorphous solids. B.S. Moorthy, B. Xie, J. Panchal and E.M. Topp, in Hydrogen-Deuterium Exchange Mass Spectrometry: Fundamentals, Techniques and Applications, D. Weis (ed.), Wiley, New York, 2016, pp. 265-278. ISBN: 97811118616499.

Immunogenicity of therapeutic protein aggregates (invited review). E. Moussa, J. Panchal, M. Joubert, L. Narhi, J. Blum and E.M. Topp, Journal of Pharmaceutical Sciences, 106: 417-430, 2016. Published in the Ronald T. Borchardt Dedicated Issue. Most downloaded articles, June 2016.

Physical characterization and innate immunogenicity of aggregated intravenous immunoglobulin (IGIV) in an in vitro cell-based model. E. M. Moussa, J. Kotarek, J.S. Blum, E. Marzsal and E.M. Topp, Pharmaceutical Research, 33/7: 1736-1751, 2016. DOI 10.�1007/�s11095-016-1914-4

Fibpredictor: A computational method for rapid prediction of amyloid fibril structures. H. T. Ghomi, E.M. Topp and M.A. Lill. Journal of Molecular Modeling, 22: 206, 2016.  DOI: 10.1007/s00894-016-3066-1

Thiol-disulfide exchange in human growth hormone. S. Chandrasekhar, B.S. Moorthy, R. Xie and E. M. Topp. Pharmaceutical Research, 33/6: 1370-1382, 2016. DOI 10.1007/s11095-016-1879-3. PMID: 26887678

Process and formulation effects on protein structure in lyophilized solids using mass spectrometric methods. L.K. Iyer, G.A. Sacha, B.S. Moorthy, S.L. Nail and E.M. Topp, Journal of Pharmaceutical Sciences, 105/5: 1684-1692, 2016. NIHMSID: 766404

Predicting protein aggregation during storage in lyophilized solids using solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS). B.S. Moorthy, S. Schultz, S. Kim and E. M. Topp. Molecular Pharmaceutics, 11/6: 1869-1879, 2014. DOI: 10.1021/mp500005v. PMID: 24816133.

Analyzing subvisible particles in protein drug products: A comparison of dynamic light scattering (DLS) and resonant mass measurement (RMM). J. Panchal, J. Kotarek, E. Marszal and E. M. Topp, AAPS Journal, 16/3: 440-451, 2014. DOI: 10.1208/s12248-014-9579-6. PMID: 24570341.

Thiol-disulfide exchange in peptides derived from human growth hormone. S. Chandrasekhar, A. Sophocleous and E. M. Topp, Journal of Pharmaceutical Sciences, 103/4: 1032-1042, 2014. DOI: 10.1002/jps.23906. PMID: 24549831.

Commentary: Current perspectives on the aggregation of protein drugs. E. M. Topp, AAPS Journal, 16/3: 413-414, 2014. DOI: 10.1208/s12248-014-9580-0. PMID: 24563118.

Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders. Moorthy, BS. Iyer, LK, and Topp, EM, Journal of Visualized Experiments (JoVE) (98), e52503, doi:10.3791/52503 (2015). Published 04/14/2015. NIHMS ID: NIHMS653055. 4/21/2015 10 110.

Structural transitions and interactions in the early stages of human glucagon amyloid fibrillation. Moorthy, Balakrishnan S., Ghomi, Hamed T., Lill, Markus A., and Topp. Elizabeth M.Biophysical Journal, 108/4: 937-948, 2015. PMCID: PMC4336368 112

Thiol-disulfide exchange in peptides derived from human growth hormone during lyophilization and storage in the solid-state. Chandrasekhar, Saradha and Topp, Elizabeth M., Journal of Pharmaceutical Sciences, 104/4: 1291-1302, 2015. PMID: 25631887 111.

Photolytic crosslinking to probe protein-protein and protein-matrix interactions in lyophilized powders. Iyer, Lavanya K., Moorthy, Balakrishnan S., and Topp, Elizabeth M., submitted to Molecular Pharmaceutics, March 5, 2015.

Cocrystalline solids of telaprevir with enhanced oral absorption. Stavropoulos, K, Johnston, S., Zhang, Y, Bhisetti, G, Hurrey, M., Hurter, P., Topp, E., and Kadiyala, I, Journal of Pharmaceutical Sciences, submitted January 14, 2015. 113.

Commentary: Current perspectives on the aggregation of protein drugs. Topp, EM, AAPS Journal, February 22, 2014. DOI: 10.1208/s12248-014-9580-0.

Predicting protein aggregation during storage in lyophilized solids using solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS). Moorthy, BS, Schultz, S, Kim, S, and Topp, EM. Molecular Pharmaceutics, 11/6: 1869-1879, 2014. DOI: 10.1021/mp500005v.

Analyzing subvisible particles in protein drug products: A comparison of dynamic light scattering (DLS) and resonant mass measurement (RMM). Panchal, J, Kotarek, J, Marszal, E, and Topp, EM, AAPS Journal, 16/3: 440-451, 2014. DOI: 10.1208/s12248-014-9579-6.

Thiol-disulfide exchange in peptides derived from human growth hormone. Chandrasekhar, S, Sophocleous, A, and Topp, EM, Journal of Pharmaceutical Sciences, 103/4: 1032-1042, 2014. DOI: 10.1002/jps.23906.

Microarrays and microneedle arrays for delivery of peptides, proteins, vaccines and other applications. Chandrasekhar, S, Iyer, LK, Panchal, JP, Topp, EM, Cannon, JB and Ranade, VV, Expert Opinion in Drug Delivery, 10/8: 1155-1170, 2013.

Photolytic labeling to probe protein-protein and protein-matrix interactions in lyophilized powders. Iyer, LK, Moorthy, BS and Topp, EM, Molecular Pharmaceutics, 10: 4629-4639, 2013. DOI: 10.1021/mp4004332 

Protein aggregation and lyophilization: Protein structural descriptors as predictors of aggregation propensity. Roughton, BC, Iyer, LK, Bertelsen, E, Topp, EM and Camarda. KV, Journal of Computers and Chemical Engineering, 58/11: 369-377, 2013.

Localized effects of hydration on lyophilized myoglobin by hydrogen/deuterium exchange mass spectrometry. 1. Exchange mapping. Sophocleous AM, Zhang J, and Topp EM. Molecular Pharmaceutics  9 (4) (2012): 718-726.  Special Issue “Advances in Biophysical and Bioanalytical Protein Characterization”.

Localized effects of hydration on lyophilized myoglobin by hydrogen/deuterium exchange mass spectrometry. 2. Exchange kinetics. Sophocleous A, and Topp EMMolecular Pharmaceutics 9, no. 4 (2012): 727-733. Special issue, “Advances in Biophysical and Bioanalytical Protein Characterization”.  

Protein G, Protein A and Protein-A-derived peptides inhibit the agitation induced aggregation of Ig. Zhang GJ, and Topp EM. Molecular Pharmaceutics 9 (3) (2012): 622-628.

Use of glass transitions in carbohydrate excipient design for lyophilized protein formulations. Roughton BC, Topp EM, and Camarda KV. Computers and Chemical Engineering 36 (2012) :208-216.

Optimizing protein-excipient interactions for the development of aggregation-reducing lyophilized formulations. Roughton BC, Pokphanh AI, Topp EM, and Camarda KV. Proceedings of the 11th International Symposium on Process Systems Engineering, I. a Karimi and R. Srinivasan (eds.), Elsevier, Oxford, UK, pp. 1351-1355, 2012.

Probing protein conformation in lyophilized powders by hydrogen/deuterium exchange: Deuterium uptake kinetics in lyophilized myoglobin powders. Sophocleous A, and Topp EM. Molecular Pharmaceutics. Invited manuscript for special issue, “Advances in Biophysical and Bioanalytical Protein Characterization”. Submitted August 17, 2011. Reviewers’ comments received November 16, 2011.

Proteins and peptides: Physical and chemical stability. Sophocleous A, Zhang J, Iyer L, Chandrasekhar S, and Topp EM. Encyclopedia of Pharmaceutical Science and Technology, 4th ed., James Swarbrick, D.Sc., Ph.D., Editor. Informa Healthcare, New York, NY. Submitted April 26, 2011.

Adhesive/dentin interface: the weak link in the composite restoration. Spencer P, Ye Q, Park J, Topp EM, Misra A, Marangos O,  Wang Y, Bohaty BS, Singh V, Sene F, Eslick J, Camarda KV, and Katz JL. Annals of Biomedical Engineering, 38(6): 1989-2003, 2010.

Thiol-disulfide interchange in the tocinoic acid/glutathione system during freezing and drying. Thing M, Zhang J, Laurence J, and Topp EM. Journal of Pharmaceutical Sciences, 99/12: 4849-4856, 2010. DOI 10.1002/jps.22206.

Effect of photoinitiator system and water content on dynamic mechanical properties of a light-cured bisGMA/HEMA dental resin. Park J, Ye Q, Topp EM, Kieweg SL, and Spencer P. Journal of Biomedical Materials Research: Part A, 93A/4: 1245-1251, 2010. DOI: 10.1002/jbm.a.32617.

Immune response to controlled release of immunomodulating peptides in an experimental autoimmune encephalomyelitis (EAE) mouse model. Zhao H, Kiptoo P, Williams TD, Siahaan TJ, and Topp EM. Journal of Controlled Release, 141: 145-152, 2010. DOI: 10.1016/j.jconrel.2009.09.002.

Protein conformation and reactivity in amorphous solids. Sinha S, Xie S, and Topp EM, in Formulation and Process Development Strategies for Manufacturing of a Biopharmaceutical, F. Jameel and S. Hershenson, eds., John Wiley and Sons, Hoboken, NJ, 2010. ISBN: 978-0-470-11812-2. pp. 493-506.

Chemical instability in peptide and protein pharmaceuticals. Topp EM, Zhang L, Zhao H, Payne RW, Evans GJ, and Manning MC. Formulation and Process Development Strategies for Manufacturing of a Biopharmaceutical, F. Jameel and S. Hershenson, eds., John Wiley and Sons, Hoboken, NJ, 2010. ISBN: 978-0-470-11812-2. pp. 41-68.

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