At Juno Therapeutics, I lead a team that is involved in the bioanalytical characterization of CAR-T cell therapies. We apply state of the art analytical tools, including mass spectrometry, to understand the process involved in making CAR-T cell therapies. I am also the analytical lead for two pipeline programs that are in a phase 1 clinical trial.

My group uses the MAM to support every aspect of process development. MAM data is utilized from molecular optimization through formulation devlopment. I lead the MAM Consortium. The purpose of the consortium is to enable the BioPharma community to implement a robust mass spec based method for biotherapeutic characterization and release of biotherapeutics from QC. The MAM Consortium has members (>170 total) from >50 companies spanning government agencies, biopharma, mass spec vendors, software vendors, reagent vendors, and CDMOs.

At Just, I will develop mass spectrometry techniques to quickly characterize biotherapeutics. We will use this mass spectrometry platform for real-time monitoring of product quality attributes and release of biotherapeutics.

• I developed a 1-D nano-spray LC/MS method for detecting host cell proteins in drug substance. This method is faster and the data are more comprehensive than other techniques used to detect host cell proteins.• I lead a team that has developed a method that integrates a MS-based multi-attribute method (MAM) into a fully compliant package required for quality control and release testing of biologics in a regulated environment.• I developed and tested the qualification experiments necessary for implementation of the MAM.• I co-developed a non-reduced MAM that has automated the characterization and quantification of disulfide isoforms for monoclonal antibodies.

• Characterizing the role of protein ISGylation during Mycobacterium tuberculosis infection.• Identified more than 1300 putative ISG15 targets in bone marrow macrophages using mass spectrometry.• Examining the effect of SUMO modification on transcription factors involved in the innate immune system.• Managing a project to characterize the phospho-proteome of bone marrow macrophages stimulated with LPS.

• Developed Theraclone’s SOP for target identification of human antibodies rescued from human germinal centers.• Identified the target of the antibody that secured Theraclone’s series B round of funding.• Developed a bead based assay to screen B-cell supernatants for specific antibodies.

• Catalogued the murine proteome using organelle isolation and mass spectrometry.• Examined the differences in the posttranslational modification profile of red blood cell membrane proteins when mice are treated with different drugs using mass spectrometry.• Optimized HPLC techniques to separate peptides and proteins to obtain better coverage of samples analyzed by mass spectrometry.

• Developed software to predict location of posttranslational modification of proteins using mass spectrometry. Optimized conditions for both yeast and mammalian systems. • Developed techniques to quickly isolate posttranslationally modified proteins by affinity chromatography. • Examined the effect of ubiquitin mediated protein degradation on peroxisome biogenesis using yeast as a model organism.• Optimized techniques to map binding domains responsible for protein-protein interactions using in vitro translated proteins. • Demonstrated that the yeast nuclear pore complex is involved in maintaining chromatin boundaries using genetic techniques.

• Developed and optimized an in vitro posttranslational modification system for determining the site and efficiency of SUMO modifying proteins. Purification of all enzymes and substrates was necessary for this assay.• First to demonstrate that SUMO modification of STAT1 affected its response to interferon-gamma.• First to show that SUMO modification of the heat shock proteins HSF1 and HSF2 affects their ability to bind DNA.• Using immunofluorescence, demonstrated that SUMO modified proteins localize to the XY body of pachytene spermatocytes.

• Examined the effect of the Thrombospondin proteins on angiogenesis using cell culture to demonstrated that type I repeats are responsible for anti-angiogenic activity of Thrombospondin 1