Nanoscale Engineering with Massive Impact: Farewell to Prof. Willem Mulder

Article by Jazz Munitz

As the BioMedical Engineering and Imaging Institute continues to rapidly expand, there have been numerous researchers and staff members who have made this institute so exceptional. It is with a grateful and saddened heart that we say goodbye to Prof. Willem Mulder, one of the first members of the original Translational and Molecular Imaging Institute, whose unhindered creativity and stoicism helped build BMEII to its current stature. To honor his impact, we sat down with him for an interview to reflect on where it all started, and how far it’s come.

Q: How did you first hear about Mount Sinai?

A: I had heard of Mount Sinai from movies and TV shows like Law & Order. Scientifically, Sinai became something mythical to me back when I was a PhD student. Reading the work from Zahi and Dr. Fuster, I was intrigued by both the science and the people behind it.

Q: When did you first meet Zahi?

A: I was working on vessel wall molecular imaging in mice back when I was a PhD student. I reached out to Zahi by email and we arranged to meet in Cologne in, I believe, September of 2005 at the annual Molecular Imaging Conference. Two months later I was on a flight to NYC (for the first time) to spend the tail end of my PhD trajectory in Zahi’s lab, from mid-November to mid-December. We were exceptionally productive together, and produced the manuscript “Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles” in a month, which was published in Magnetic Resonance in Medicine.

Q: How did the Nanomedicine program start?

A: In April 2006 Zahi called me out of the blue, as he had set up meetings with Dr. Drayer and Dr. Charney for my recruitment. I remember spending time in Central Park prior to these meetings where I had sunburnt my head terribly, and went into the meetings looking like a tomato. How could I have known that the NYC sun is burning hard in April? In October 2006, I moved to the US to work on a preclinical molecular imaging program, but I was mostly interested in developing nanomedicine into an immunotherapy modality, which is exactly what BMEII’s Nanomedicine Program is internationally renowned for today.

Q: Who was your first student?

A: My first student was a Dutch medical student, Mark Lobatto who got to spend an externship at Mount Sinai. He was introduced through his aunt to Dr. Fuster and then ended up with Zahi. Mark and I have completely different personalities, but hit it offandhesetupallof our first nanomedicine studies in atherosclerotic rabbit models. We remained in touch and through the Amsterdam Medical Center, I was able to hire Mark as a PhD student to come to Mount Sinai and work on his research. He was awarded his doctorate cum laude (top 2 percentile in Dutch Academia).

Q: What do you remember of moving into the Hess Center?

A: Since I travelled between NYC and the Netherlands very frequently, I was fortunate to spend the first part of my tenure in a basement where I had no sense of time. We were very productive even with limited means, but our research program really levelled up when we took our lean and mean attitude to Hess. I can’t think of a better imaging facility in the world. The infrastructure is unique, particularly in how it’s managed by Radiology and BMEII.

Q: What was the first big paper you published, when you really felt that you’d made it?

A: I still don’t feel that I’ve made it, but there have certainly been milestone papers:
1) Lobatto et al. Nature Reviews Drug Discovery, the first time that we’d shared with the world our vision of nanomedicine in cardiovascular disease;

2) Raphael Duivenvoorden, Jun Tang et al. Nature Communications, which we had worked on for five years, beginning in 2008. It was our first study where we fully integrated immunology and demonstrated the application of nanomedicine for innate immune regulation;

3) Binderup, Duivenvoorden, Fay et al. in Science Translational Medicine. As one of the reviewers eloquently stated: “A tour de force.” Zahi and I worked on a large NHLBI Program of Excellence in Nanotechnology, which started in 2010. This study is the climax of that program. We pulled of nano-immunotherapy of atherosclerotic inflammation in large animal models, facilitated by clinical PET/MR imaging;

4) Max Senders et al. in Nature Nanotechnology, where we demonstrated the use of new nanotech and multimodal imaging methods to study immune cell dynamics in living mice;

5) Bram Priem et al. Cell, demonstrating the use of our proprietary nanobiologic technology as an efficacious and safe immunotherapy for cancer.