Zhu designs drug delivery systems to test nanovaccines for brain and skin cancer
By Blake Belden
Having a research laboratory on a medical campus, Guizhi Zhu, Ph.D., will often cross paths with cancer patients, and it’s during those instances that he is most driven to continue his work.
“I sometimes feel helpless because I can’t do much for them in that moment other than saying some kind words,” he said. “Those are the moments that help me focus on my research to potentially have an impact that can change or improve therapeutic outcomes for cancer patients.”
Guizhi “Julian” Zhu uses innovative drug delivery platforms to test the efficacy of novel immunotherapeutics for a variety of disease types including skin, liver, brain, colorectal and breast cancers.
He joined VCU Massey Cancer Center as an associate member of the Developmental Therapeutics research program in 2018, and he is an assistant professor in the Department of Pharmaceutics and Center for Pharmaceutical Engineering and Sciences at the VCU School of Pharmacy.
Leveraging an extensive background in engineering, chemistry and pharmacology, Zhu designs targeted drug delivery systems and develops cancer nanomedicines such as nucleic acid nanovaccines for enhanced therapeutic benefit. Nanovaccines are vaccines that dispense microscopic particles into the immune system to stimulate a response against cancer cells, and they hold promise for treating disease more effectively than existing vaccines. Zhu tests a variety of nucleic acids, including immunomodulatory DNA/RNA, gene-expression modulation DNA/RNA, drug-encoding mRNA or gene-editing nucleic acids.
Zhu currently holds several grants to support studies on nanovaccines for glioma, a tumor of the brain and spinal cord, and melanoma, the deadliest form of skin cancer.
Under the mentorship of Steven Grossman, M.D., Ph.D., deputy director of Massey, Zhu holds an American Cancer Society Institutional Research Grant (ACS-IRG) to study the combination of an immunotherapy and an immuno-activating chemotherapy to treat melanoma.
He is also one of the principal investigators , together with Kristoffer Valerie, Ph.D., and Paula Bos, Ph.D., members of the Cancer Molecular Genetics research program at Massey, on a Massey Pilot Project that will explore the combination of a nanovaccine, immune re-energizing drugs and radiation therapy to treat glioma in mouse models.
“This project is really exciting because there isn’t a durably effective treatment option for glioma,” Zhu said. “We hope that by using radiation we can jump start the tumor microenvironment to make immunotherapy more effective.”
He is a KL2 Mentored Clinical Research Scholar under the mentorship of Douglas Sweet, Ph.D., and Sandro da Rocha, Ph.D., an Endowment Fund awardee from the VCU Wright Center for Clinical and Translational Research and a VCU Presidential Research Quest Fund recipient.
Zhu leads a research team of six postdocs and graduate students as well as multiple undergraduate students and visiting scholars.
He grew up in China where he earned a bachelor’s degree in biotechnology from Nankai University. Zhu moved to the United States, where he earned his Ph.D. in medical science – physiology and pharmacology – and also completed a postdoctoral fellowship in cancer nanomedicine at the University of Florida. He finished a second postdoctoral fellowship in cancer immunotherapy and bioimaging from the National Institute of Biomedical Imaging and Bioengineering in Maryland. During this time, Zhu collaborated in famous and well-established laboratories to engineer and image nanomedicines. It was following this fellowship when he centered his work around cancer immunotherapies.
“Because the nature of my work is heavily focused on cancer immunotherapy, the scientific combination of pharmaceutics and cancer offers an ideal environment for me at Massey,” Zhu said.
Zhu has published more than 70 articles in peer-reviewed journals, including Nature Communications, Proceedings of the National Academy of Sciences, Journal of the American Chemical Society, ACS Nano, Angewandte Chemie, among others. His publications have been cited by peers more than 4,500 times in the past five years, according to Google Scholar. Zhu is a member of the American Chemical Society, the Oligonucleotide Therapeutics Society and the Society for Immunotherapy of Cancer. He received a Distinguished Scientist Award from the National Institutes of Health in 2017, and he was awarded the Alan M. Gewirtz Memorial Fellowship by the Oligonucleotide Therapeutics Society (2013), among other awards.
Zhu lives with his daughter and mother in Richmond, and they await the arrival of his wife who is close to finishing her doctoral degree in food science and nutrition in Maryland.
VCU receives $2.7M to study use of anti-inflammatory medicine for treatment of heart failure
Hearts that are failing become inflamed and swollen — doctors have known that for years.
But researchers at VCU Pharmacy and VCU Health wondered what would happen to people with failing hearts if they treated the inflammation as a cause of the illness rather than a symptom. Would the patients feel better?
Initial studies seemed to say yes. The results were convincing enough that the National Institutes of Health took the unusual step of funding a larger study directly through a $2.7 million grant over five years.
The grant will fund a clinical trial with 102 heart-disease patients. Researchers will investigate if reducing inflammation in the heart muscle can improve the patients’ health and reduce the need for hospitalization. Researchers expect to begin enrolling patients later this year. (More about this trial and enrollment criteria.)
It is the fourth NIH grant for the research team that is co-led by Benjamin Van Tassell, Pharm.D., vice chair for clinical research and associate professor in the VCU School of Pharmacy Department of Pharmacotherapy and Outcomes Science, and Antonio Abbate, M.D., Ph.D., vice chair of the Division of Cardiology in the VCU School of Medicine. The current study will build on encouraging results from a smaller 2016 study also funded by the NIH.
The researchers are investigating the possibility that inflammation could be a major cause of heart failure, rather than simply a symptom of the condition.
“The heart is a muscle,” Van Tassell said. Like other muscles, when inflamed it becomes swollen and difficult to move. Swelling could have major effects on the heart’s ability to pump blood and could result in heart failure and death.
Heart disease remains the leading cause of death in the United States, according to the Kaiser Family Foundation. The condition is difficult to treat and expensive to manage. Nearly 1 in 4 people hospitalized for heart failure return to the hospital within 30 days of leaving, according to a 2017 study published in the journal Risk Management and Healthcare Policy.
Earlier efforts by scientists to connect heart problems to inflammation have shown inconsistent results, possibly from focusing on the wrong types of inflammation, Van Tassell said. In the past few years, however, Abbate and Van Tassell have led multiple clinical trials using a drug originally developed to treat rheumatoid arthritis to target a specific type of inflammation that is driven by a protein called Interleukin-1.
In the VCU researchers’ 2016 study of 60 heart-failure patients with a recent hospitalization, those who received treatment achieved lower levels of inflammation and were able to exercise longer than patients who did not receive treatment. In the course of six months, only one patient receiving long-term anti-inflammatory treatment went back to the hospital. Nearly one-third of the patients who did not receive the anti-inflammatory treatment were hospitalized in the same period.
Last year, a large-scale study from the pharmaceutical company Novartis used a similar drug to reduce inflammation. The Novartis research found the number of heart attacks was cut by about 15 percent. The VCU study will examine if a similar approach can help people with heart failure.
Pharmacy students present at pharmacoeconomics conference, win best poster award
By Purva Parab (VCU-ISPOR Chapter President 2017-2018)
Hrishikesh Kale, a fourth-year Ph.D. candidate in the VCU School of Pharmacy, received the Best Student Poster Research Presentation Award at the recent conference of the International Society for Pharmacoeconomics and Outcomes Research.
The top 10 percent of posters out of 1,600 submitted were considered for the award this year; three including Kale received the award. Kale won for his poster, “Economic Burden of Renal Cell Carcinoma among Older Adults in the Targeted Therapy Era.” His adviser is Dr. Norman Carroll.
Other VCU School of Pharmacy students presenting posters at the conference include second-year master’s student Purva Parab (“Patterns of Use and Quality of Life Associated with the Utilization of Antidepressants amongst Cancer Patients with Depression”), whose adviser is Dr. Pramit Nadpara; and Yiran Zhang (“Transplanting Kidneys from HCV Positive Donors Into HCV Negative Recipients in the Era of Direct Acting Antiviral Therapy: A Cost Effectiveness Analysis”), a second-year VCU-Indivior fellow currently working with Carroll.
Graduate students from the Department of Pharmacotherapy and Outcomes Science (Division of Pharmacoeconomics and Health Outcomes) and the members of the VCU chapter of the International Society for Pharmacoeconomics and Outcomes Research represent the VCU School of Pharmacy every year and exhibit their research at the ISPOR international annual conference. (Read about some previous years’ conferences here and here.)
This year’s annual meeting was held in Baltimore. More than 4,000 people from more than 40 countries attended the conference, whose theme was “Real-World Evidence, Digital Health, and the New Landscape for Health Decision Making.”
The VCU-ISPOR team included Kale, Parab, Zhang and Ph.D. student Elena Fernandez.
VCU-ISPOR students chapter also hosted a VCU alumni dinner at the conference. Parab, the president of VCU-ISPOR chapter, received funding for the alumni dinner from the VCU development office.
“We would like to thank [former School of Pharmacy development director] Ellen Carfagno for arranging the funds for the dinner,” Parab said. “It was great!”
Augmented reality can revolutionize surgery and data visualization, say VCU researchers
By Leah Small
The practical uses for augmented reality — which superimposes digital information onto real world surroundings — seem endless. Technologists have envisioned futuristic applications such as glasses that allow wearers to visualize turn-by-turn navigation in real time and immersive gaming headsets. Recently, scientists have focused on harnessing the technology for intellectual pursuits.
Virginia Commonwealth University researchers are leading utilization of AR for medical and research purposes. An interdisciplinary team of faculty and students led by Dayanjan “Shanaka” Wijesinghe Ph.D., assistant professor in the department of Pharmacotherapy and Outcomes Sciences in the School of Pharmacy, is developing augmented reality platforms that could improve surgical approaches, refine personalized medicine and serve as a research tool.
The Med-AR program, which is optimized for the Microsoft HoloLens AR platform, renders 3-D models of CT and MRI scans, and allows users to interact digitally. In February, VCU Medical Center surgeons used the application to prepare for two complex cardiac surgeries. Another version of the program is frequently employed to create 3-D models of complex biochemical networks for scientific research.
“Our technology has the capability to democratize medicine across the globe,” Wijesinghe said. “The 3-D surgical and biochemical network models can be shared worldwide for collaborative planning of complex surgeries and research.”
The operating room
In many respects, the AR application surpasses detailed 2-D medical imaging in its ability to offer surgeons realistic presentations of anatomy, said Dan Tang, M.D., the Richard R. Lower professor in cardiovascular surgery in the VCU School of Medicine.
Tang is the surgical director of heart transplantation and mechanical circulatory support. He and his team recently donned headsets to prepare for two surgeries, one to mend a central portion of the heart and the other to repair leaks around two artificial valves.
The surgeons used 3-D reconstructions of CT scans generated by Med-AR to view areas of concern in the way they would appear on the operating table. Programmed verbal commands allowed the surgeons to rotate the models, move them and cause some parts to go transparent to view hidden anatomy.
“It really gives you a sense of where structures lie in relation to other structures while planning operations,” Tang said. “It’s particularly helpful for trainees who are still learning to translate the preoperative screen imaging to the live intraoperative findings.”
Tang expects the technology to improve alongside that of medical imaging and AR hardware.
“Augmented reality represents a leap forward,” Tang said. “When physicians went from plain film X-rays to digitized CT scans, we were provided with more detailed images.”
The majority of this information is still displayed in 2-D slices, and 3-D reconstructions of the images require further development. However, the VCU teams’ interactive, 3-D models present an intuitive imaging platform that surgeons can use to plan operations, and as a tool to educate patients on their disease process.
Wijesinghe envisions more ambitious surgical applications for the technology. His lab is working to develop an experience that is shared in real time between users during surgery and remote users, with the option of video and voice recording. Eventually, he aims to expand the software to overlie scaled 1-to-1 images on top of the operative field to provide supplemental information in real time.
“Being able to overlay the 3-D virtual reconstruction on the patient is akin to providing something like X-ray vision to the surgeons,” Wijesinghe said. “They will be able to see the patient, but also the structure underneath that they need to reach during the operation.”
Wijesinghe and Tang also collaborated with Vig Kasirajan, M.D., the Stuart McGuire professor and VCU Department of Surgery chair; Alex Valadka, M.D., professor and VCU Department of Neurosurgery chair; and the VCU da Vinci Center to perfect the technology.
Rendering biochemical networks
The research initiative stemmed from the need to understand biochemical pathways and interactions. This helps scientists explain and predict cellular functions that impact biological mechanisms such as disease progression and metabolism.
Biochemical networks, which are graphs scientists use to visualize biochemical interactions, provide the key to understanding biochemical pathways.
Data points called nodes represent molecules such as enzymes or metabolites. Lines drawn between the nodes define how the molecules interact.
Biochemical networks allow scientists to see the bigger picture but they take up an enormous amount of space when displayed in 2-D, which makes AR’s 3-D capabilities convenient.
“The issue we were running into is that complete biochemical networks are extremely complex, so no matter how much they are magnified, we cannot even display the data on multiple screens,” Wijesinghe said. “We needed a different technology and it made sense to generate immersive biochemical networks that are not limited to screen space.”
The system has some similarities to existing technologies, Wijesinghe said, but costs much less and is much more portable.
Wijesinghe’s next steps are to apply the AR technology’s biochemical network visualization capabilities to personalized medicine. The goal would be to visualize the effect of drug interactions on biological mechanisms within a patient profile.
For example, a scientist could use the technology to visualize a drug’s ability to improve an individual’s metabolism. Biological indices would be obtained from the patient to create the biochemical network, and drug molecules and metabolites would be represented by nodes. Scientists would use various visual aids, such as affected nodes going dark, to predict drug interactions.
“We solved the problem of visualizing networks,” Wijesinghe said. “Now, what we are working on is visualizing how specific drugs can impact an entire network.”