Sunny Zhou, professor of chemistry and chemical biology, recently earned the 2022 Spark Fund from the Center for Research Innovation. This fund will go towards his work on spatial and temporal activation of protein therapeutics. Read below to learn more about professor Zhou and his innovative work!
What led you to pursue a career in the field of chemistry and chemical biology?
I entered the field of chemistry because I failed. When I finished high school in China, the students took a three-day, seven-subject exam that determined which college they would attend. Though my score was good enough for Peking University in Beijing, it fell short of the cut-off for the physics major, a subject that I excelled in high school and was my first choice. I ended up majoring in chemistry as my second choice.
In retrospect, chemistry is a better match with my personality and overall interest. I have always been interested in medicine—my dad was a pharmacologist and my mom taught medical botany. On a side note, I thought about going to medical school, as I could have been a good physician as well. The reason I did not become a physician was because I liked to mess around and tinker, and of course, one cannot mess around with human patients. When I was in college, I found physics pretty clear-cut and biology a bit too complex, but chemistry had a good balance of well-defined concepts and manageable complexity. So, my setback in the college entrance exam was actually a blessing for me. Students often think their interests and field of study are fixed, but they are not; they evolve over time.
There are generally three pillars that define scientific research: first, the mechanistic investigation– understanding how each system works and is exemplified by many studies in biology and chemistry. Second, synthesis or engineering– creating something, such as designing and developing a drug. And third, the development of tools, including techniques, methodologies, and instrumentation. What I like about chemistry and what I am doing now– developing pharmaceutical and protein drugs– is that I am involved in all three of these concepts.
Tell us about your research on spatial and temporal activation of protein therapeutics which earned you the spring 2022 Spark Fund. Why is this research important?
When creating a drug to combat a disease, making a molecule that will kill the diseased cells is easy. For example, remember when the former president suggested using bleach to kill the corona virus? He was correct in the sense that bleach would indeed kill the virus. But the challenge with developing a safe drug is that we do not want to kill the healthy cells. The problem with his idea is that the bleach would also kill other things in our bodies that we need to survive. This is a fundamental and vexing issue in drug development: finding a molecule that kills the diseased cells without harming the healthy ones. The scientific term is therapeutic index.
When trying to improve therapeutic index, one common approach is to find some biological selectivity. For example, cancer cells may have certain biological markers (i.e., at much higher levels than the healthy cells) that one can target with drugs. This is not always the case, however. These differences are not always easy to find because we have many different types of cells that can be remarkably similar. As such, for many diseases, biology simply does not present viable targets.
As a general solution, we wanted to introduce a physical aspect of drug activation: light. Let’s say one’s right hand has some medical condition, but the left hand doesn’t. There are many aspects to consider when taking a pill to treat the skin condition, such as how to avoid the liver, the left hand, and a large-scale response. The drug needs to be very selective in order to avoid these complications, which is a tall order. Now, imagine that one takes a pill that is inactive in the absence of light (what we call a pro-drug), so there will be no toxicity throughout the body. Then, we shine light on only the right hand to activate the pro-drug in just that area. This is the beauty of photo-medicine. Light confers exclusive spatial control. Temporal control is another advantage to this approach, as one can administer the drug and wait until a certain time to activate it with the light. This gives you more control over the drug’s release, whereas a traditional drug will start working soon after it is taken. In photo-medicine, we combine physics, biology, and chemistry, to provide markedly enhanced selectivity.
We began applying this concept to eye cancer (ocular melanoma) but are using this as a lead for other diseases. Light can deliver to many places in the body, not just skin. The three general categories are the skin, cavities (such as the colon, throat, oral cavities, and lungs), and solid tissues (such as tumors). People used to think delivering light to these places was hard, but it has become quite routine; for instance, we already do it with procedures such as colonoscopies. Light can reach almost anywhere, and the beauty is that any place it does not touch will not be affected at all.
Why is this research important? Because photo-medicine, relatively speaking, is still a new-comer. It is also complex, requiring the combination of physics, chemistry, and biology. Because of this, our work is to map it out and shape its future. There is a lot of promise. We are, in some ways, the trail blazers for the field of photo-medicine.
Due to its interdisciplinary nature, this research requires active teamwork. I want to highlight the cutting-edge research of Professor Bryan Spring, one of the co-PIs on the grant. He is in the Physics Department and is an expert on photo-medicine.
What does this award mean for you and your future work?
In some ways, the research is going much quicker than we expected. Typically, we conceive ideas, write proposals, and if lucky, receive grants, and then may invent something after many years’ work. In this case, we actually invented the new chemistry, published the first paper and received the patent without having a major grant. Now we are entering what is often called “The Valley of Death” where it moves from basic research to successful innovation, which is hard to get grants for. This Spark Fund helps to fill this critical gap.
This award is also crucial for further development. During the review process, we received a lot of good feedback from the panel. In addition, the CRI guidelines also prompted us to critically self-evaluate, polishing our ideas and plans. Their criticism is very helpful in shaping the direction of our work. Of course, the money is great, but the feedback is equally valuable. There is also the recognition and publicity that comes with the award, which is always helpful.
Tell us about your experience as an editor for the mAbs and Antibodies Therapeutics journals.
I am essentially a gatekeeper of three parts: research quality, future direction of the field, and the development of the next generation scientists. Peer review is the gold standard for science. The editor is in some ways a gate keeper for the peer review process. The most important aspect, I think, is the quality. Making sure the quality of the work is being checked. Part of being an editor is to recruit critical and constructive reviewers.
As editors, we sometimes need to guide the direction of the field as well. We choose what to publish partially based on what we want the direction of the field to be. People may not always realize this: sometimes we reject certain papers from the journal simply for this reason, even if the work itself is solid and useful. That has even happened to me with journals that have been publishing our work for years; the journals ended up rejecting our work at some point because the direction of the field has shifted. Whatever was innovative before becomes more routine later. As editors, we do this on an individual manuscript level and also through thematic issues. For instance, the journal Antibody Therapeutics will highlight the concepts of AntibodyPlus, which encompasses research on various antibody-conjugates for a myriad conditions and diseases.
Coming from the lens of being a professor in addition to an editor, I also see my role as an obligation and opportunity to develop the next generation of reviewers. I always actively recruit and provide opportunities for young scientists to be reviewers. Typically, only seasoned scientists are invited to be reviewers, but I like to give these budding scientists chances to do it and learn as they go. When young scientists learn how to review, they also become better authors and scientists themselves because they know what is expected for proper science and communication.
I also personally learn a lot from serving as an editor. A majority of each review is shared with the authors, but there is a certain part that is only shared with the editors, which typically is very critical and brutally honest, nasty even. As an editor I get to see all of that which is super insightful. Though time consuming and bearing lots of responsibilities, being an editor is a very rewarding experience and a way to give back to the community.
You have affiliations with The Barnett Institute for Chemical and Biological Analysis as well as the COS Biology and Biotechnology departments. How does your research meet at the intersection of these fields?
My view is that most people are doing interdisciplinary research now. The “home department” is basically only relevant for the sake of categorizing into teaching units. For example, I could easily be a faculty in the bioengineering department instead of chemistry as my work is so interconnected.
My work with Barnett is more on the analytical side, for example analyzing proteins and ensuring the substance quality and stability for the protein pharmaceuticals, so it also falls under the general umbrella of biotech. Through the work of my Industry PhD student Chirs Chumsae when he was at AbbVie, we worked on Humira, the world’s best-selling drug with an annual sale of $20 billion until surpassed by COVID vaccines.
What other work is your lab Sunnyland working on at the moment?
We are continuing to develop new methods of controlling drug releases with stimuli other than light, such as by the tumor microenvironment. We are also expanding into new diseases such as wound healing, cosmetics, and pain management.
Is there a way right now for students, postdocs, other researchers to get involved in your lab?
Yes! We welcome all levels of students in our lab as long as the student can make a long-term commitment—at least two semesters. Training people to be independent and productive takes time.
What advice do you have for young researchers in the realm of chemistry?
The first thing is that one needs to truly understand the fundamentals. The understanding of chemistry lies upon the relationships between structure, property, and reactivity. To be a good chemist, one should develop a good mental picture of these things. A good starting point is definition. I often find that even people who have worked in their fields for years cannot define their major precisely and concisely. Even the dictionary definition is often not very good. So give a try and come up a good definition yourself.
The second thing is the importance of self-learning. The coursework, even in graduate school, really is introductory. There are lots of things you can learn on your own that go deeper and broader. I never took a formal class on cancer biology; I’ve had to learn on my own. This includes other soft skills like writing. This is why in my class I assign homework for my students before the very first lecture. People are often surprised at how much they can learn on their own. Most of my students are more than capable of doing their first assignment before my first lecture.
My third piece of advice is to find good mentors and develop a supportive network. Lots of people are hesitant to reach out for help from faculty and others, but most of us are very happy to help! Give a try and you will find that most faculty members are very approachable outside the classroom. Finding a good mentor can be difficult but it is also important and rewarding. A good mentor doesn’t necessarily have to be prominent by whatever standards. It comes down to personal style and other aspects that make a mentor the best fit for you. I have been very fortunate to have lots of great mentors throughout my career. Also, keep in touch with them. I still talk to my high school teachers!
Katie Hemphill, Director of Technology Ventures and Talent Network at CRI, comments on Sunny’s work and achievements:
“Sunny has made the most of entrepreneurship ecosystem offerings, from engaging with the CRI’s Spark Fund to Northeastern University’s Center for Entrepreneurship Education’s NSF I-Corps Site. Business education, mentorship, and funding are key to bringing a technology from bench to market. Sunny understands this and leverages all available to him. I encourage PIs interested in commercializing their research through spinning out a company ask Sunny about his path and learn from his experience! I am excited to support Sunny and team as they work towards commercialization with their Spark Fund award.”
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