The following is the seventh entry in a Q&A series highlighting selected Clinical Proteomic Tumor Analysis Consortium (CPTAC) researchers and their work. Join us as we discuss metabolomics, collaboration, and the future of the field with Jennifer Kyle, PhD, a Staff Scientist at Pacific Northwest National Laboratory. Transcript is edited for clarity.
Q: Could you please provide a brief overview of your academic and professional journey?
Dr. Jennifer Kyle: My journey’s been an unusual one. My academic degrees are in geology even though I now study human health. What connects my professional journey is looking for biomarkers. Early in my career, this was focused on finding biosignatures of life in extreme environments to enable scientists to potentially find evidence of life on early Earth and/or other planets or moons. Now, I study human systems in hopes of identifying biomarkers of disease to enable scientists to develop early diagnostic tools or potentially apply/develop treatments to improve health outcomes.
Q: Could you describe your current work with PNNL and how that fits in with CPTAC?
JK: My work at PNNL is managing and working closely with a team to further develop our metabolomics and lipidomics capability for applications across human health and environmental systems.
For CPTAC, I am currently the co-chair of the CPTAC Data Generation and PTM Working Group and leading the metabolomics platform efforts for PNNL. I work closely with Dr. Liu and the metabolomics team at PNNL and conduct the lipidomics data analysis. What makes the work compelling is knowing people have donated their tissues in hope but also trust that scientists will do what we can to improve treatments and outcomes, if not for their generation, but the next. It is a responsibility, from what I have seen, that is taken to heart by all those involved.
Q: Could you share a project you’re proud of, or one you worked on that taught you valuable lessons?
JK: A project I am proud to have contributed to is the NIH funded Undiagnosed Diseases Network (UDN, https://undiagnosed.hms.harvard.edu/). Participants who are accepted into this program are often the only person or one of few individuals who are suffering from their medical mystery, and they have been seeking help for years. In working with the clinicians and researchers within the UDN, it was clear that everyone involved truly wanted to help the participant and their family obtain and diagnosis and ideally improve their health circumstances. My contribution to the UDN from 2016-2018 was to manage the Metabolomics Core and conduct lipidomics analyses on biofluids collected from probands (and their families) with undiagnosed diseases. What were undertook was to try and find out what’s metabolically different in blood and urine for a person with a unknown disease. This was a really challenging task as there’s so much variability from person to person. However, the end goal, to help people and get them answers--It's something I was really happy to contribute to and be a part of.
Q: How important is collaboration within your space at PNNL and with CPTAC?
JK: Collaboration is key. At PNNL, we’re highly team science-oriented. We don’t do anything on our own; we have scientists preparing samples, running instruments, processing data, and biostatisticians analyzing it. Everyone contributes, so we can bring findings and hopefully results to help people with cancer.
Q: What unmet needs do you see in your field, and how do you think they could be addressed?
JK: Well, in metabolomics and lipidomics, there’s still so much to discover. One major challenge is detecting all the metabolites and confidently identifying them. With proteins and genes, we can map pathways and understand what’s being altered, but it’s harder with metabolites. The community is working to improve this, especially in lipidomics, where individual lipids don’t fall into clear pathways. Another big challenge is integrating all the data — genomics, proteomics, metabolomics, lipidomics — in a way that’s meaningful.
A lot of people are working on this, and technology is rapidly evolving. Mass spectrometry, for instance, is advancing to better analyze and detect small molecules. So, I think we’ll make significant contributions within our lifetimes. I also see the next generation coming and that’s part of the reason why I’m so optimistic. At PNNL, the younger scientists are much more interdisciplinary. Many of them have lab-based computational experience. This enables them to understand an entire workflow or pipeline, enabling them to focus on the biological interpretation of findings. I believe this will accelerate the progress and discoveries the next generation will achieve. I’m excited to see what they’re going to do in the next few years.
Q: Do you have any advice for a someone hoping to follow a similar path?
JK: I’d say engage your curiosity. My career path hasn’t been straight, but it’s all connected. I went with what I found interesting and, eventually, it all comes together. Sometimes the success can be incremental but remember the end game and keep working towards it. The other one I would say is to be true to yourself. Sometimes we’ll do things that feel mundane, or we are unsure about. Instead, create your own path. I think you’ll get somewhere that’s really novel, and you’ll enjoy it.