By Alison Caldwell, Bigelow Science Communication Fellow
|Qiangzhe “Oliver” Zhang (left) at the annual Research Expo at the UC San Diego Jacobs School of Engineering.|
San Diego, Calif., May 20, 2020 -- When Qiangzhe “Oliver” Zhang was still a high school student in China applying to colleges in the United States, UC San Diego’s chemical engineering program at Jacobs School of Engineering was at the top of his list. “I knew they had this very new, very innovative nanoengineering program,” he said. “It’s one of a kind, and that got me really excited.”
Now, almost eight years later, Oliver Zhang is working at the leading edge of biomedical research under Liangfang Zhang in the Nanomaterials and Nanomedicine Laboratory, developing new technologies that could completely change how scientists combat viruses like HIV and SARS-CoV-2.
As an undergraduate, Oliver Zhang had a lot of fun meeting other students in the same major. “We were able to form life-long friendships afterward,” he said. “These are really good, brilliant friends that I’m still keeping in close communication with, long after graduation.”
But when it came to other activities outside of the classroom, Oliver Zhang needed more of a challenge. “I had a hard time figuring out what to do with myself, because I had no idea of what scientific research actually was at that time,” he said. “Luckily, there was a professor in my department who seemed really cool. He was really generous in offering me a lot of advice during our first meeting, knowing that I had zero research experience, and he was able to offer a lot of mentorship on academic life and introduce me to the exciting work happening in his lab.”
That professor turned out to be Liangfang Zhang, whose lab is focused on creating biomimetic nanotechnologies to solve complex challenges in human disease. After some background reading and a few more conversations, Professor Zhang recruited Oliver Zhang to join his lab as an undergraduate research assistant. “Since then,” Oliver Zhang said, “I’ve been having so much fun, I just can’t stop.”
Within months, Oliver Zhang was deeply embedded in the lab, taking over a project that had been passed down by a PhD student working on “nanosponges” - polymer nanoparticles coated in fragments of cell membrane proteins. These nanosponges can mimic the body’s cells and act as decoys to bind and inactivate harmful pathogens and toxins. As an undergraduate, Oliver Zhang worked to develop these nanosponges for use against pore-forming bacterial toxins.
“In a lot of infectious diseases, bacteria harm us by producing pore-forming toxins that punch holes in the membrane of our cells and kill them,” Oliver Zhang explained. “So we used the same idea in the opposite direction: we put that same membrane onto nanoparticles, so now the toxins are punching holes in the membrane-coated nanoparticles and won’t harm real cells.”
The team was still just getting started with the application of this technology, and Oliver Zhang was reluctant to leave it behind as he was applying to graduate schools. “I considered Stanford, and Johns Hopkins,” he said, “But after I talked to faculty there, I realized that the research in my current lab is just so exciting and cutting edge that I can’t think of another arena that would fit my interests so well. And I knew that if I stayed in Professor Zhang’s lab, I would be able to get a quick start in graduate school and get more rapidly involved in projects in the field of nanomedicine.
“I was also really excited about working with more of the faculty here at UC San Diego,” Oliver Zhang continued. “During undergrad, I could see that we had a lot of young and hardworking faculty working on multiple different projects that were all really new and exciting. By staying here, I’d be able to meet a lot of new grad students in a variety of fields whose expertise could benefit my research.”
As a graduate student, Oliver Zhang has expanded his research to include nanosponges made not only from the membranes of red blood cells, as he studied during undergrad, but also using leukocytes - a type of white blood cell. These circulating blood cells can bind to signaling molecules called cytokines. Increased production of cytokines is a hallmark of many different kinds of infections and inflammation, and too many cytokines can lead to overactivation of the immune system. In the lab, Oliver Zhang has been testing using leukocyte-membrane-coated nanosponges to turn down the overheated communication between cells to prevent tissue damage, like that seen in sepsis.
Other projects Oliver Zhang has worked on include using neutrophil nanosponges to block signaling in rheumatoid arthritis as a potential treatment for the inflammatory joint disease. He also contributed to a major breakthrough using T-cell coated membranes to bind and block HIV viral particles from infecting immune cells, which may provide new hope for treating this difficult-to-tackle virus.
“What I really like about this work is that it doesn’t involve any therapeutics,” said Oliver Zhang. “It uses the biological principle of how things work: how toxins attack cells, how viruses invade, how cells talk to each other. We’re using it to design something to modulate this communication without using any drugs.”
During his time at UC San Diego, Oliver Zhang has collected a number of first-author publications, and at the time of writing, was gearing up to defend his dissertation in just a few short weeks. Afterward, he plans to continue wrapping up some of his current projects in the lab, and looks forward to continuing his career in the biotech industry working on pharmaceutical research.
“One thing that really got me interested in nanomedicine in the first place is the idea that for a lot of diseases, it’s not that we don’t have the right drug to treat it - it’s that we can’t get the drug to the right spot. They mostly get lost in circulation,” Oliver Zhang said. “So drug delivery is one thing that nanomedicine can contribute in the future - we can design these particles to directly deliver therapeutics to the right place. There’s a lot of versatility in the way we can manipulate nanomedicine technologies.”
But the field is not without its challenges. “Because the field is so new, it’s constantly evolving very fast,” said Oliver Zhang. “Overnight, you’ll see a lot of new research work coming out in all of the top journals in nanotech and nanomedicine. So a major challenge is just keeping up with the pace of the field; but I see a lot more opportunities there than anything else.”
In the future, Oliver Zhang hopes to get involved more on the translational side of nanomedicine. “What I’ve been doing so far has been mostly on developing novel and exciting platforms to treat diseases, and in many cases, we’re still far from applying them into human use. I want to go into industry to narrow the gap between nanomedicine research and clinical use.”
Even as Oliver Zhang prepares to defend his PhD - via video call, since campus is still closed - he has advice to share for potential Jacobs School of Engineering students: “Get involved in research! There are so many new labs that are flourishing with exciting data in all different fields - immunology, batteries, nanomotors, so many different things that are definitely cutting edge and pretty much the best in the country, or even in the world. As an undergrad, you’re sitting right next to these exciting research fields - you can’t just pass on those opportunities.”
Oliver Zhang’s first author papers:
1. Zhang, Q.; Fang, R. H.; Gao, W.; Zhang, L.* “A biomimetic nanoparticle to ‘lure and kill’ phospholipase A2”, Angewandte Chemie International Edition 2020, doi: 10.1002/anie.202002782.
2. Zhang, Q.; Gong, H.; Gao, W.; Zhang, L.* “Recent progress in capturing and neutralizing inflammatory cytokines”, CCS Chemistry 2020, in press.
3. Zhang, Q.; Dehaini, D.; Zhang, Y.; Zhou, J.; Chen, X.; Zhang, L.; Fang, R. H.; Gao, W.; Zhang, L.* “Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis”, Nature Nanotechnology 2018, 13, 1182-1190.
Highlighted: Nature Nanotechnology 2018, 13, 1098-1099 (News and Views)
Nature Reviews Rheumatology 2018, 14, 622.
Science Translational Medicine 2018, 10 (459), eaav0341.