Zongjie (Daniel) Wang in the lab at CZ Biohub Chicago. (Credit: Dale Ramos, Chan Zuckerberg Initiative)

As a young child in China, Zongjie (Daniel) Wang was a natural tinkerer. He built his own radio, and soon after, his own PC — both when he was only 10 years old. “I always liked to put pieces together and make them functional,” he says. 

When it came time to choose a path for college, electrical engineering seemed like the perfect fit. At the time, he admired innovative computing technology for rendering digital 3D models, and wanted to learn how to develop the hardware for 3D computing. But as a master’s student at the University of British Columbia, Wang found it challenging to find the money to support the miniature computer circuits he had hoped to develop. So, with his advisor’s help, he shifted gears and found a niche in biotechnology. 

After completing his master’s dissertation on 3D bioprinting for engineering artificial tissues, Wang went on to study at the University of Toronto under Edward Sargent, then a professor of electrical engineering, and Shana Kelley, then a professor of biochemistry. Both are now at Northwestern University, and Kelley is also the president of Chan Zuckerberg Biohub Chicago. Wang’s research involved developing tools to predict the risk of cancer spread by capturing circulating tumor cells, or CTCs. But he didn’t stop there. Wang, Kelley, and their colleagues also wanted to figure out how to destroy CTCs, preventing cancer spread altogether. And they’re very close. 

As a consulting scientist for cTRL Therapeutics, a biotechnology company founded by Kelley, Wang helped develop methods for identifying, isolating, and amplifying tumor-specific immune cells for personalized cancer therapy. After several successful preclinical trials on animal models, the cTRL Therapeutics team is aiming to launch Phase I clinical trials next year, Wang says. 

Now, as a new CZ Biohub Chicago Group Leader, Wang is focused on piecing together novel technologies and devices to help fight disease at the cellular level. We recently caught up with Wang to discuss his foray into biomedical engineering and the vision for his new group at the Biohub. 

For a long time, you were on track for a traditional career in electronic or computer engineering. That changed in graduate school when suddenly you needed to learn a significant amount of biology. Was that a difficult transition to make?

It was actually pretty fun because I didn’t learn biology in an ordinary way. I had no biology background at the time and didn’t have any idea how to culture a cell. So, I applied my engineering mindset to learning biology. For example, I wanted to know: What were the inputs? What were the outputs? What are the processing units in the biological system? These are high-level assumptions that usually you’ll make for studying an engineering system. But biology is not that easy. It’s very complicated, very chaotic. That’s why there is demand for designing something that is small, but also accurate and powerful, so that we can better measure and define complex biological systems. 

What kind of research does your group do at the Chicago Biohub?

Right now, we have two directions. The first goal is to better understand immune cells. This is a continuation of my research on liquid biopsy and rare cell engineering. The hope is that we can detect circulating biomarkers in the cells, proteins, DNA, RNA, or metabolites to predict disease dynamics. For example, if there’s an autoimmune disease, can we detect early signs of the disease using a non-invasive blood test? Or eventually, if we can use a smartwatch or other wearable device to do continuous monitoring, that would be great. 

CZ Biohub Chicago’s moonshot idea is to develop 3D tissue constructs with embedded microstructures that will facilitate continuous sensing, sampling, and omics analysis of inflammation.

The other direction is our moonshot idea. We want to better understand how the immune system reacts to certain pathogens in order to find early clues of disease initiation. With that in mind, we find there is a demand for new technology, because at the moment, researchers use single-cell RNA sequencing to gather lots of information regarding, say, how cells are different at the single-cell level. But usually for these kinds of assays, you will lose some of the tissue-level information, such as how the cells talk to each other in their native state or native organization. That’s the limitation of single-cell RNAsequencing.

But now we are in the era of spatial omics. So we can take a tissue and fix it into a wax block, and then you can use spatial technology to take samples in a spot-by-spot manner. This lets us analyze how cells talk to each other, but the problem is that once the tissue is fixed, you only have that one time point. I’m trying to develop a way to do spatial omics on live cells so we can continue sampling and be able to understand how the cells talk to each other at different time points. If we have the capability to sample different locations and different time points, we could trigger an inflammation in one area of the tissue, then over time, see how the inflammation spreads and how the immune system responds to that. 

The projects you’re describing sound pretty challenging. What stops you from becoming discouraged when things aren’t coming together as you hoped?

I think failure is not a problem. My philosophy when designing new systems is that if you’re going to fail, fail quickly so that you can seek other directions. It’s a pretty rare case for a new design to work perfectly after only a few rounds of development, but if with every run I can see a slight improvement, that will keep me positive. 

What about the Chan Zuckerberg Biohub enticed you to join?

The vision for high-risk, high-impact research was immediately a philosophy I was very attracted to and was a major driver for me to join the Biohub. Shana has also been a great colleague for the last few years, so I was eager to continue to work with her. 

Another huge benefit of the Biohub model is that I can focus on doing research — hands-on research — because I don’t need to spend days or weeks at a time writing grant proposals. At the Chicago Biohub, I feel like I can be more creative and start to think about how I can better position my technology for the future, and how I can better contribute to the community. I also appreciate the emphasis on community building and collaboration at the Biohub. 

Your group is only a few months old. Are you hiring, and what are you looking for in new group members?

I’ve hired two scientists to work with me so far, and we’re hiring a postdoc to work with us who will start in the summer. We hope to continue to grow the team. 

We’re looking for creative people with open mindsets who are motivated to learn about new technologies. They don’t need to come from the bio field in order to create useful products for biomedicine. The Chicago Biohub provides a great opportunity to do amazing work in a big city with lots of resources nearby, and we’re highly collaborative. 

What do you like to do for fun outside of work, or what do you wish you had more time to do?

To be honest, I haven’t done much outside of work in the last maybe 10 years. But before that, I liked to cook a little bit, especially Japanese ramen or sushi. And I just moved to the U.S. a little less than two years ago, so now I’m interested in exploring the national parks and seeing more of what Chicago has to offer.

If you could give your younger self just starting out in engineering or biotech some advice, what would it be?

I would say to stay creative. Stay hungry. Stay motivated.