03/10/2026
By Kwok Fan Chow

The Kennedy College of Science, Department of Chemistry, invites you to attend a Ph.D. Dissertation defense by Liyunzi Liang entitled “Investigating the Origins and Effects of Charge Heterogeneity in Two Therapeutic Proteins.”

Date: Tuesday, March 31, 2026
Time: 10 a.m.
Location: Perry Hall, Room 415

Committee:

  • Advisor: Jin Xu, Ph.D., Department of Chemistry, University of Massachusetts Lowell
  • Matthew Gage, Ph.D., Department of Chemistry, University of Massachusetts Lowell
  • Carl Lawton, Ph.D., Department of Chemical Engineering, University of Massachusetts Lowell
  • Dongming Xie, Ph.D., Department of Chemical Engineering, University of Massachusetts Lowell

Abstract:
Even though protein therapeutics are designed to be homogeneous and undergo extensive purification, final products often exhibit significant heterogeneity. Charge variants, arising from intrinsic post-translational modifications (PTMs) and various degradation pathways both in vitro and in vivo, are frequently observed in both recombinant biopharmaceuticals and endogenous proteins. These variants often manifest as shifts in isoelectric point (pI), leading to changes in protein conformation, stability, and functionality. Such alterations can result in reduced potency, adverse immunogenic responses, and modified bioavailability, all of which are directly linked to efficacy and safety — the two determinants for the success of drug development. Therefore, the identification and characterization of charge variants are essential steps in biopharmaceutical analysis. This study developed and applied comprehensive analytical strategies, including imaging capillary isoelectric focusing (icIEF), ion exchange-high performance liquid chromatography (IEX-HPLC), size exclusion chromatography (SE-HPLC), SDS-PAGE, glycan labeling, site-specific N-glycan mapping, and multi-level liquid chromatography-mass spectrometry (LC-MS), to fractionate and characterize charge heterogeneity. Two development-stage products were investigated as models: a monoclonal antibody (mAb) of the IgG1 class and an Fc-fusion protein, representing two major categories of biotherapeutics commonly used in clinical practice. By understanding the sources and impacts of charge heterogeneity, this study will facilitate the optimization of drug design and manufacturing processes to minimize undesirable variants, enhance homogeneity, and improve product stability and efficacy. Moreover, the methodologies developed through this research can be applied broadly to study charge heterogeneity and its effects on other proteins with charge variants.

All interested students and faculty members are invited to attend.