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Tools & Techniques Cardiovascular, Omics

Lessons I’ve Learned, With Jenny Van Eyk

There is much we don’t know

I was born in Northern Ontario, Canada and went to a small high school. There were just three students in my advanced calculus class and hardly anyone went to university, but I got a place studying chemistry at the University of Waterloo. For a long time, I thought that you went to university simply to study the traditional subjects – I didn’t even know that you could become a researcher or engineer. In my first year, I was taking chemistry courses and, as I’d expected, the things we were learning had been known for hundreds of years. Then one day I took a biology course, during which the professor told us about the newly published fluid mosaic model for lipid membranes. He said “we think this is right, but we don’t know for sure.” I was amazed – it hadn’t occurred to me that there were things even professors didn’t know, and that I might be able to add to our collective knowledge. I switched my course to biochemistry and fell in love with discovery.

The power of peptides

I took some persuading to embark on my PhD. I was happy working as a technician in a great lab, publishing papers, and I didn’t want anything to get in the way of my science. But my PhD in peptide chemistry (with Bob Hodges at University of Alberta) allowed me to publish my first landmark paper; I created a synthetic peptide made up of just 12 amino acids that could replace cardiac troponin I (cTnI) in the muscle contractile apparatus.

After my PhD, I spent four months in Heidelberg, Germany, studying the physiology of muscle fibers. The Heidelberg group used skinned muscle fiber bundles – a perfect model for muscle contraction, created by peeling away the membrane of muscle fibers to expose the contractile proteins, and adding calcium to make them contract and relax. It was a short placement, but the timing was fantastic – I arrived just as the group discovered how to remove just cTnI from the muscle fibers. We were able to use the 12 amino acid peptide I developed during my PhD to replace cTnI and were delighted to find that the fibers would contract and relax as normal. It showed me how powerful amino acid sequences are. If you hit the right sequence of just a few amino acids, you can replace the function of whole proteins.

The work was a big departure from the basic science I had been doing at Alberta. I wanted to connect the pieces of the puzzle and relate the biochemistry of muscle contraction to real physiological mechanisms. Such multidisciplinary research was very rare at the time – most scientists stayed within their own narrow field. Luckily for me, cTnI became a major biomarker in cardiology, and I was mentored by some great clinical chemists and cardiologists working with emerging medicines.

Science changes lives

Another short post doc early in my career had a profound effect on me. I was back at Alberta, looking at cTnI as a biomarker in heart transplantation. Part of my job was going to the hospital to collect blood samples and on one of my visits I met a transplant patient who really stuck with me. He was a young man, but when I went to collect a blood sample the day before his surgery he was lying in bed, unable to move. His damaged heart simply couldn’t pump enough blood to his muscles to allow them to move. When I returned, just a couple of days after surgery, he was up and walking around the room. I was blown away by the change – he’d gone from being close to death to looking forward to an almost normal life. We all say we are in translational science to help people, but that was the moment I saw what that really means.

A leader brings out the best in others

My next post doc was another physiology lab, this time in Chicago, with John Solaro. I went there not just to learn science but to learn how to lead. John is a fantastic leader and my time in his lab really reinforced my views on what was important. He showed me that wherever you are, you have to be there completely. When you are home with your family, be 100 percent focused on them, but once the kids are in bed and you sit at your computer to work, totally focus on your work. You have to learn to segregate your brain – and to live in the moment.

The most important thing he and Bob taught me was that being a leader is all about the people that you surround yourself with. You need to create an environment that lets them be at their best – an environment where they are supported and where knowledge is freely shared – not one where you are thinking of your own success. Those lessons stood me in good stead once I became the head of a proteomics center at Johns Hopkins.

Bigger data need better tools

Leaving Canada to take up a position at Johns Hopkins as Director of the Proteomics Innovation Center in Heart Failure allowed me to continue to expand the scope of my research. I wanted to be able to work directly with physicians and physician–scientists so that I could better understand clinical processes and where we could best focus our efforts. I didn’t just want to look at a single diagnostic, I wanted to map out a whole clinical domain and look at how we can make the entire continuum better.

It quickly became apparent that while data is getting bigger, it won’t help you unless it is a) really quantitative and b) you have enough samples to attempt to look at whole populations.

I decided that I wanted to start a research institute to focus on how we train and equip the next generation of scientists. We need to go beyond case–control animal studies, where (n) might be as low as six. Instead, we need tools that let us vary animal systems in many different ways over time. That requires workflows for sample prep, mass spectrometry and computation. We had been working on those tools for years, but we really needed a dedicated center (and collaborative industry partners) to look at how we can take biomarkers right through the pipeline and into a commercial product.

I moved to Cedars-Sinai in 2014 to achieve that ambition, as Director of the Advanced Clinical Biosystems Research Institute. Research at Cedars-Sinai is firmly embedded into the hospital, so it’s an ideal place for a cross-discipline approach. My current role is allowing me to build a research institute from the ground up – and that means hiring in people with diverse skills, but who are all focused on the end goal of clinical translation. We want to do great basic research, but we must always ask “Why?” And if the answer isn’t to improve patients’ lives, we need to go back to the drawing board.

Collaboration is crucial

Translation is all about bringing people together. A research or industry scientist may have spent 10 years learning how to do mass spectrometry analyses, while a physician spent the same 10 years learning how to treat patients. You can’t expect them to then spend another 10 years learning each other’s trades as well, so we need to form partnerships early on. But we do need each partner to gain just enough understanding of other fields to work effectively together, otherwise projects are likely to be derailed by false assumptions. It’s not just scientists versus clinicians: even within science we all speak different languages – the language of GWAS is very different to that of clinical chemistry or computational science. I want to create an environment that breaks down those barriers for next-generation scientists, because that is the only way we are going to get new products onto the market quickly. At the Institute we share pipelines and technology, and bring in new faculty to add to our collective expertise. When we bring in new postdoctoral fellows, we don’t assign them to one group, we put them between groups, to build bridges. Thankfully, it’s getting easier and easier to find people who share that vision. Every generation is getting more comfortable with multidisciplinary work.

You can speak to 100 clinicians and hear about 100 solutions they desperately need to improve patients’ lives. How do you decide where to focus your energy? Often, I think it comes down to your environment; who are the scientists and clinicians around you and what are the compelling questions they are facing? For example, an area I’m particularly focusing on now is women’s heart health. Cardiovascular disease is the number one killer of women worldwide, and at the Cedars-Sinai Heart Institute I’m surrounded by people working on women’s health in the Barbra Streisand Women’s Heart Center – from populations, to epidemiology, to basic science.

We want to do great basic research, but we must always ask ‘Why?’ And if the answer isn’t to improve patients’ lives, we need to go back to the drawing board.

An unexpected joy for me has been the strength of the regenerative medicine program at Cedars-Sinai. I now work with Clive Svendsen in our regenerative medicine program, and other groups from John Hopkins and USD Gladstone, on induced pluripotent stem cells. We take cells from patients with neurological disease and transform them into motor neurons for in vitro studies. My group has been involved with ensuring quality control of the cells. Now, we’re starting to think about biobanking – banking induced pluripotent stem cells from large numbers of patients and healthy individuals and using them to investigate the pathways involved.  It’s a new paradigm for us, so we’re having to think about how we can best apply the tools available to us. It’s an exciting new slant to my research.

Don’t lose your humanity in science

Being a scientist is an amazing job. In fact, it’s not even a job to me – it’s a passion. But science can be a really hard business to be in. You are always being told you aren’t good enough – grants get rejected, peer reviewers criticize your work. It’s a very negative environment in some ways. That’s why it’s important not to lose sight of the human side of science. For example, we can’t continue to lose (mostly) female scientists just because they have a child – we need to be more flexible. Those few years when a parent has young children at home are so short in the context of a whole career. You have to accept that life is complicated and scientists are human beings just like everyone else. No-one is perfect. Can you imagine how boring and unapproachable you would be if you were? All I expect from my team and collaborators is to do their best, don’t be afraid to ask questions and respect each other. I look for people who share my values – if you shout at a member of my team, I probably won’t choose to work with you.

My career has spanned from biochemistry to clinical translation, and even to entrepreneurship, and I can’t wait to see where it takes me next.
Tomorrow’s scientists will be better than ever

I wasn’t trained in proteomics – if anything I was a reductionist, replacing proteins with a few-amino-acid-long peptide. That is powerful, but what was missing from my training was to look at the broader impacts, and understand the system as a whole. Nowadays, we train proteomics students to think about the bigger picture. We’re seeing a new breed of scientist – they go where the data drives them, even if that means crossing disciplines or specialties, and they feel confident in working with different experts to pinpoint the right questions and make sure their data are robust.

I hope that the Institute will change over time. In fact, I think it would be terrible if it didn’t. The new Research Institute is all of us – what it becomes over the next five or ten years will be a combination of all of our dreams and aspirations.

Keep changing threads

Someone once asked me “Where do you want to be in five years’ time?” I hope I can never answer that question completely, because that would mean I’m not open to change. I do know that I want to have an impact on medicine – to help people to survive longer and with a better quality of life, whether that is by saving hospitals time and money in diagnosis or developing biomarkers for targeted therapies. My career has spanned from biochemistry to clinical translation, and even to entrepreneurship, and I can’t wait to see where it takes me next.

When I was a young girl, I read a story that has stayed with me ever since. The author describes the fabric of our lives as the thread of an ornate rug – every time we make a decision or change direction, we introduce a new color or pattern. Some people rarely change course – their rugs are even and symmetrical – while others are a riot of different colors and patterns, constantly growing and changing. I always thought that was the type of life I wanted to have – unique, colorful, joyful… and perhaps a little eccentric!

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About the Author

Jennifer Van Eyk

Jennifer Van Eyk is Director of the Advanced Clinical Biosystems Research Institute at Cedars-Sinai Medical Center, Los Angeles, CA, USA.

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