An Interview with Shawn Owen, Assistant Professor of Pharmaceutical Chemistry at the University of Utah

Shawn Owen

We sat down over a virtual cup of coffee to interview Dr. Shawn Owen, Assistant Professor of Pharmaceutical Chemistry at the University of Utah. Owen is an experienced pharmaceutical scientist with a demonstrated history of success in the higher education industry. Skilled in antibody engineering and bio-conjugation chemistry applied to developing therapeutic and diagnostic platforms.

Editor:
Can you tell us more about how your lab and its research focus? And how you are utilizing protein engineering and bioconjugation techniques in developing therapeutic and diagnostic platforms to enable the next generation in precision medicine?

Shawn Owen:
We are interested in understanding and developing protein-based therapeutics and diagnostics. More specifically, we are focused on understanding current antibody-drug conjugates (ADCs) - how to make different variant ADCs and how different components affect the stability and efficacy of these hybrid biomolecules. We are also interested in creating new diagnostic platforms built on antibodies fused to split-enzymes. Understanding protein structure is important to our work because structure is linked to function.

Editor:
Why is protein characterization important for your work, and what do you look for in a good characterization technique?

Shawn Owen:
Understanding protein structure is important to our work because structure is linked to function. We need to be able to analyze the primary, secondary, and tertiary structure because changes to any of these characteristics can have a significant impact on stability, binding, or even enzymatic activity. Because we are an academic lab, we are often limited by the amount of material we have; that means we value characterization techniques that are sensitive and might even be not-destructive and allow us to recover the analyte. Unfortunately, we are often limited by the availability and affordability of new and high-quality instruments.

Editor:
What toolbox of technologies do you use to characterize proteins?

Shawn Owen:
We use several different overlapping and orthogonal technologies to analyze because we are interested in all aspects of protein sequence and structure. For example, we use mass spectrometry to verify peptide sequence and intact molecular weight, size exclusion chromatography to analyze homogeneity and purity, differential scanning calorimetry to assess stability, infrared and Ramen spectroscopy to understand secondary structure, as well as crystallography to determine tertiary structure.

Editor:
How have things changed since you started working in the protein characterization space? How do you think the industry will develop technologically?

Shawn Owen:
I only started working deeply in protein engineering and characterization about six years ago. Even in that relatively short amount of time, we've seen complex analysis become routine and instruments with increasing sensitivity at smaller volumes. For example, mass spectrometry of large proteins like antibodies are used as part of regular QA/QC and even hydrogen/deuterium exchange (HDX) can be adapted to higher-throughput analysis.

Editor:
What are the biggest challenges in protein characterization analysis that your lab is facing today? And what gaps new technology fill for you?

Shawn Owen:
As mentioned, the major issue we often face is the amount of material we can produce for analysis; as such, we need techniques that are sensitive using smaller volumes and lower concentrations. Another challenge is trying to understand protein structure and function in more realistic, complex systems including in high protein environments like that found in plasma.

Editor:
How do you see secondary structure analysis as a necessary component in your characterization of proteins?

Shawn Owen:
Any structural challenge may have significant consequences on the stability and function of the biomacromolecules we study. Changes in secondary structure are good indicators of potentially damaging stress-induced changes that can result from temperature, shear stress, and storage conditions. We can quickly assess different parameters using secondary structure analysis without having to rely on functional assays or more complex tertiary analysis.

Editor:
Would you explain the work done with MMS applied to your analysis and the benefits of MMS to your research with high sensitivity and resolution in secondary structure analysis?

Shawn Owen:
We had some observational evidence that different formulations would affect the stability of ADCs. In our first experience with MMS, we wanted to see if we could identify any structural changes that would correlate with the poor stability. Using MMS, we identified changes in three beta-sheet structure bands and observed that formulations with greater deviations from our control were directly correlated with level of instability. Importantly, this was the first time that we could analyze these samples directly in the different buffers and at a concentration much lower than other techniques.

Thank you Shawn, for your great insights.