We were lucky to catch up with Weikai Cao recently and have shared our conversation below.
Weikai, we’re thrilled to have you on our platform and we think there is so much folks can learn from you and your story. Something that matters deeply to us is living a life and leading a career filled with purpose and so let’s start by chatting about how you found your purpose.
I discovered my purpose through a deep appreciation for the impact biotechnology and drug development have on saving and improving lives. From a young age, I witnessed the loss of loved ones to diseases such as cancer, Alzheimer’s, and most recently, SARS-CoV-2, which shaped my desire to contribute to healthcare.
Biotechnology in the U.S. has made remarkable strides in developing therapeutic proteins, particularly monoclonal antibodies and adeno-associated viruses (AAVs). Monoclonal antibodies have become essential in treating cancers and viral infections, while AAV-based gene therapies have been Food and Drug Administration (FDA)-approved for conditions like spinal muscular atrophy and Duchenne muscular dystrophy. However, there still remain some issues to solve during drug development, such as low-throughput and low-efficiency in drug analysis.
During my time at Beijing University of Chemical Technology, I was inspired by these opportunities and decided to pursue biomolecular research in the U.S. This led me to the PhD program at the University of Notre Dame, where I focused on liquid chromatography-mass spectrometry (LC-MS), a powerful tool used throughout drug development, from preclinical trials to quality control. My research aims to streamline bioanalysis using LC-MS to support applications in biotechnology, pharmaceutical industry and public health , improving efficiency and potentially enabling automation in drug analysis.
Now, as I join Insmed Inc. as an LC-MS Scientist, I look forward to using my expertise to contribute to the development of therapies that can make a tangible difference in people’s lives.
Appreciate the insights and wisdom. Before we dig deeper and ask you about the skills that matter and more, maybe you can tell our readers about yourself?
In the research during my PhD, I have been focusing on developing state-of-the-art liquid chromatography-mass spectrometry (LC-MS) tools to support applications in biotechnology, pharmaceutical industry and public health.
Glycosylation refers to the attachment of glycans, which are composed of various sugars with different masses, to specific amino acids of proteins. It plays a critical role in the bioactivity of proteins. For example, glycosylation of the SARS-CoV-2 Spike affects viral entry into host cells. Similarly, the glycosylation of erythropoietin and monoclonal antibodies significantly influences their pharmacokinetic and pharmacodynamic properties. Therefore, the FDA has listed glycosylation as a critical quality attribute that must be monitored before approval.
Protein glycosylation analysis by LC-MS requires digestion by proteases, which usually takes a few hours or even overnight for more complete digestion. This puts such a heavy burden on the throughput of protein analysis using LC-MS. Besides, proteins need to be extracted and denatured from tissue samples or fermentation broth using urea or sodium dodecyl sulfonate (SDS). Unfortunately, urea and sodium dodecyl sulfonate (SDS) are not compatible with LC-MS. Particularly for SDS, even modest amounts of SDS can lead to overpressure on liquid chromatography and signal reduction in mass spectrometry.
To solve these issues related to LC-MS, I utilized spin columns or 96-well plates to enhance the efficiency/throughput of protein digestion, purification and SDS removal. These techniques has been successfully applied to sequence and glycosylation analyses of commercial monoclonal antibodies (Kanjinti, Bevacizumab, and Rituximab), analyses of host cell proteins and in-house expressed monoclonal antibodies, as well as quantitative LC-MS assay development of Trastuzumab in mouse serum. This prototype could prove valuable for real-time monitoring of product glycosylation, ensuring the consistency and efficacy of therapeutic agents. It also enables the quantitative LC-MS assay development of proteins that require SDS for solubilization or denaturation.
There is so much advice out there about all the different skills and qualities folks need to develop in order to succeed in today’s highly competitive environment and often it can feel overwhelming. So, if we had to break it down to just the three that matter most, which three skills or qualities would you focus on?
Looking back, the three most important qualities in my journey through biotechnology development have been curiosity, perseverance, and a strong work ethic.
1. Curiosity:
The 21st century is often called the “Bio-century” because of groundbreaking discoveries in DNA, RNA, proteins, and their glycosylated forms. Understanding how these biomolecules function is crucial for developing new therapies and effective vaccines. With the field constantly evolving, maintaining curiosity is key to leading the field. I foster this quality by reading updated journal articles every week, attending research conferences and staying updated on the latest bioanalytical techniques. For those early in their journey, I recommend cultivating a habit of continual learning—stay curious about new developments, explore emerging technologies, and always ask questions.
2. Perseverance:
In research, things rarely go as planned, and failure is a part of the process. Experiments may fail for various reasons, leading to frustration. At this moment, perseverance is essential for pushing through these setbacks. I often remind myself that while the goal is bright, the path is filled with obstacles. For those just starting out, embrace challenges as opportunities. Persistence will help you uncover solutions that others may overlook.
3. Work Ethic:
A strong work ethic is the “catalyst” that drives progress. No matter how much curiosity or perseverance you have, success in research requires dedication and consistent effort. Working hard ensures that you stay ahead in a competitive field, and it helps you avoid discoveries getting scooped up by others. My advice is simple: put in the hours, focus on your goals, and get thorough in your work. Science will reward those who are persistent.
What’s been one of your main areas of growth this year?
In the past 12 months, my biggest area of growth has been the international recognition of my research in developing state-of-the-art liquid chromatography-mass spectrometry (LC-MS) tools for applications in biotechnology, the pharmaceutical industry, and public health.
Due to my expertise in biochemistry, bioanalysis, and mass spectrometry, I was invited to serve as a peer reviewer for Rapid Communications in Mass Spectrometry, a leading journal in the field. So far, I’ve completed three peer reviews. Being asked to review work for such a prestigious journal is a clear recognition of my standing as an expert in LC-MS, further motivating me to advance my skills and contribute to the field.
Additionally, a project I’ve led on SDS removal is currently under peer review at Journal of the American Society for Mass Spectrometry, another authoritative journal. The removal of SDS from biological samples has broad implications in proteomics, protein characterization, and bioanalysis, and has garnered positive feedback from reviewers. Both reviewers and the editor think our manuscript is a good fit to this journal. Publication in such journals represents the acknowledgement of my work’s value and innovation.
These experiences—serving as a peer reviewer and publishing in top-tier journals—have significantly boosted my confidence and expertise. Looking ahead, I’m excited to continue developing advanced LC-MS tools to improve drug quality control, glycosylation analysis, and the overall advancement of therapeutic protein development.
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