Thomas McLellan

Background

About Thomas McLellan

Developed a high-resolution mass spectrometer Walkup solution for protein chemists with workflows for intact mass, enzymatic digestion, and small molecule analysis. This enabled the analysis of recombinant protein mass, monitoring of post-translational modifications, sample purity, protein sequence verification, and quality confirmation of cofactors and ligands. The system features eight column chemistries for method selection via drop-down menus, and Healex ChemLaunch software for desktop data processing access. Over 80 scientists were trained to use the system • Developed TEMS, a semi-quantitative method based on Speed Screen technology, focusing on the protein instead of small molecules for monitoring covalent engagement. The SEC step served as a quench to remove unbound small molecules without altering sample pH. This allowed techniques like dephosphorylation and deglycosylation of the protein before analysis, enabling interpretation of engagement. TEMS has been used to establish target engagement, specificity, covalent reversibility, selectivity, kinetics, and competitive screening • Ran QC on novel polymers for the development of LNP’s in the mRNA vaccine program using MALDI-Tof. Determined Mn, Mw, and DPi of the polymer, confirmed structure and relative purity of the sample • For the CoVid vaccine program determine the glycosylation pattern of the spike protein and the levels at the site using O18 water. In subsequent vaccines, determined the level and complexity of the glycosylation at new sites of due to mutations in the protein • Developed analytical methods using chromatographic and mass spectrometer platforms to aid receptor-mediated delivery of CRISPR-Cas9 for cell-specific gene editing. This included determining ligand/protein conjugation ratios, localizing conjugation events, measuring free ligand levels before and after cleanup, assessing co-vector peptides bound to RNP post-incubation, evaluating RNP/Cas9 stability, and identifying Cas9 multimers through various gel electrophoresis techniques. • Developed and validated quantitative biomarker methods for biotranslational research utilizing mass spectrometry. In instances where stable heavy labeled internal standards were unavailable, we utilized Pfizer's resources to biocatalyze the creation of these internal standards to facilitate the studies • Worked with colleagues utilizing photo/chemical probes to determine ligand binding sites on protein therapeutic targets