Assistant Professor (2018 - present) 

Department of PharmaceuticsSchool of PharmacyVirginia Commonwealth University, Richmond, VA.

Associate Member, Developmental Therapeutics Program, Massay Cancer Center

 

Postdoc fellow (2014 - 2018)

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH, Bethesda, MD. (Advisor: Dr. Shawn Chen)   

 

Ph.D. (2008 - 2013), Medical Sciences - Physiology & Pharmacology

Interdisciplinary Program in Biomedical Sciences, College of Medicine, University of Florida, Gainesville, FL. (Advisor: Dr. Weihong Tan)

 

B.S. (2004 - 2008), Biotechnology, Nankai University, Tianjin, China

Awards and Honors

2018                KL2 Mentored Clinical Research Scholar Award, National Center for Advancing Translational Sciences

2017                Top 15 Abstract, World Molecular Imaging Congress Meeting

2017                Distinguished Scientist Award, NIH CSSA

2014                Travel Award, Oligonucleotide Therapeutics Society

2013                Dr. Alan M. Gewirtz Memorial Scholarship, Oligonucleotide Therapeutics Society  

2013                Early Career Investigator Fellowship, Nanotechnologies in Cancer, the New York Academy of 

                        Sciences           

2008                Grinter Fellowship, College of Medicine, University of Florida

2008                Travel Award, College of Medicine, University of Florida 

2005-2007       Outstanding Student Fellowship, Nankai University     

Funding

2019                Presidential Research Quest Fund, VCU

2019                VA-VCU Pilot Grant

2019                American Cancer Society Institutional Research Grant (ACS IRG)

2019                Endowment Fund Award, Wright Center for Clinical and Translational Research, VCU 

2019                Pilot Project, Massey Cancer Center, VCU

2018                KL2 Mentored Clinical Research Scholar Award, National Center for Advancing Translational Sciences

 

Dr. Guizhi (Julian) Zhu leverages his multidisciplinary training to develop novel biotechnologies and medicines that interrogate biomedical questions, solve biomedical problems, and develop novel diagnostics and therapeutics (theranostics). Julian strives to lead a productive and visionary research and training program that works together to advance pharmaceutical science and health science.

 

Julian’s graduate research in Dr. Weihong Tan’s lab at the University of Florida involved leveraging the structural and functional programmability of nucleic acids to design and screen nucleic acid aptamers as specific targeting ligands against molecular and cellular cancer biomarkers. By further combining aptamers and scaffolding nucleic acids, they invented aptamer-mediated nucleic acid molecular devices and nanostructures for sensitive sensing of cell microenvironment and drug delivery (Zhu, et al., Chem Comm, 2012). Julian developed a myriad of molecular and nano- aptamer-drug conjugates (ApDCs) for anticancer drug delivery (Zhu, et al., Bioconjug Chem, 2015). In molecular ApDCs, Julian developed bispecific ApDCs to overcome cancer heterogeneity in drug delivery (Zhu, et al., Chem Asian J, 2012), co-led the invention of “molecular train” ApDCs in which each aptamer was automatically synthesized to deliver many prodrug copies (Wang, Zhu, et al., J Am Chem Soc, 2014), and transformed a natural drug-DNA adduct formation into a simple, efficient, and biostable ApDC platform (Zhu, et al., NPG Asia Mater, 2015. Trinh, Zhu (co-first), et al., Plos One, 2015). Julian is also a pioneer in ApDC nanomedicine. For instance, to address the issues of low drug payload capacity and high cost, Julian invented DNA nanostructures termed as nanotrains to efficiently deliver theranostic agents to target cancer cells (Zhu, et al., PNAS, 2013). By harnessing the attractions of nanotrains, Julian went on and assembled nanotrains in situ on the membrane of target cancer cells, so as to interrogate single cell microenvironment in a real-time and pinpoint manner (Zhu, et al., Angew Chem Inter Ed, 2013). While these studies fascinated him, Julian quickly realized the limitations of nucleic acid nanomedicines, such as limited biostability in vivo, dynamic nature of nanostructures, and limited payload capacity of nucleic acid moieties in one nanostructure due to conformational hindrance. All these limitations are associated with the hybridization-based methodology of nanostructure synthesis. Inspired by the efficient synthesis of genomic nucleic acid in many viruses, Julian invented a novel methodology of nucleic acid nanostructure synthesis, in which size-tunable nucleic acid nanoparticles were efficiently synthesized in an enzymatic reaction using a designer DNA template, and the particles were simultaneously biomineralized by a generally recognized as safe (GRAS) components. Taking advantage of the designability of templates, such nanoparticles can be synthesized with a myriad of functions. By incorporating cancer-specific aptamers and drug-binding DNA into these nanoparticles, they synthesized nanoparticles, with extremely high biological and thermal stability, for targeted drug delivery in multiple drug sensitive and drug-resistant cancer (Zhu, et al., J Am Chem Soc, 2013. Hu, Zhao, Zhu, et. al., Angew Chem Inter Ed, 2014. Mei, Zhu (co-first), et al., Nano Res, 2015). Aside from drug delivery, Julian also studied using aptamers for cancer diagnostic PET molecular imaging (Zhu, et al., Bioconjug Chem, 2017.), EGFR (Cheng, Zhu (co-corresponding author), et al., submitted), and Glypican 3 (Cheng, Zhu (co-corresponding author), et al., in preparation.)

 

Julian has a long-time interest in tumor immunotherapy that harnesses the patient’s own sophisticated immune system to fight against cancer (Zhu, et al., ACS Nano, 2017. Chen, Zhang, Zhu, et al, Nat Rev Mater 2017). Bioengineering and pharmacology can tremendously help innovate and improve cancer immunotherapy. In pursuing this passion, he then did a postdoc with Dr. Shawn Chen at NIBIB, in collaboration with immunologist Dr. Robert Seder Lab at NIH Vaccine Research Center and super-resolution microscopy pioneer Dr. Hari Shroff at NIBIB. Julian married the expertise in molecular/nano- engineering and bioimaging, and physiology and pharmacology to develop novel immunotherapeutic nanomedicines, and exploited multiscale system bioimaging to interrogate their pharmacological behaviors to comprehensively understand and improve medicine development. In his early research in this field, he leveraged the ability of DNA nanoparticle assembly to integrate thousands of therapeutic DNA CpG oligonucleotides into one single particle. Then he developed immunotherapeutic nanoparticles that had robust immunostimulation in antigen presenting cells, and dramatically inhibited the growth of melanoma (Zhang, Zhu (co-first), et al., ACS Appl Mater Interfaces, 2015. Zhu, et al., Nanoscale, 2016.). Realizing that monotherapy of CpG nanovaccine only slowed down tumor growth even after intratumor injection, Julian was motivated to recruit synergistic role players both to his team and to his nanovaccines: by partnering with polymer chemists and immunologists, he set out to develop immunotherapeutic nanovaccines that not only delivered CpG, but also synergistic shRNA, tumor associated antigens and tumor neoantigens. In one project, Julian further innovated the methodology of nucleic acid nanostructure synthesis, in which both designer DNA and RNA can be simultaneously synthesized in the same solution, and the resulting DNA (e.g., CpG) and RNA (e.g., immunomodulatory shRNA) were integrated into one single microparticle. Further, to enhance in vivo delivery efficiency to lymph nodes, he and colleagues synthesized cationic PEG-grafted polypeptides that can shrink the microparticles into nanocapsules. Additionally, the hydrophobic polypeptides coated on nanocapsules entails the incorporation of hydrophobic tumor-specific neoantigen peptides. The resulting CpG/shRNA/neoantigen nanovaccines proved efficient at cellular delivery and in vivo delivery to lymph nodes, resulting in potent T cell activation and robust immunotherapy (Zhu, et al., Nature Communications, 2017). This technology innovation also drove the development of in-situ synthesized shRNA-PLA/drug nanomedicine that deliver tumor neoantigens or shRNA for cancer immunotherapy or chemotherapy, respectively (Ni, Zhang, Zhang, Zhu (co-corresponding ), et al., Advanced Materials. Ni, Zhu (co-corresponding ), et al., in preparation.)

 

Technology innovation drives the advancement of medicine development. In recognition of the limitation of current synthetic nanomedicines, including nanovaccines, in terms of large-scale reproducible manufacture of quality control, as well as long-term safety and integrity, Julian developed an interest in pursuing nanomedicines that are derived from endogenous biologics and/or derivatives of clinically safe compounds. In doing so, he turned his interest to albumin, one of the most abundant, long-lived, and extremely stable biomolecules in vivo. Indeed, albumin has been explored as drug carriers or composites for more than 40 years by approaches of albumin-drug conjugation or fusion, and noncovalent albumin-drug binding. Among various albumin binders, Dr. Chen’s group is interested in Evans blue, an albumin binding small molecule that has used in patients. Dr. Chen’s group has developed a toolbox of Evans blue derivatives that not only retained albumin binding ability but also have an array of reactive groups for customized conjugation to other theranostic agents. Julian leveraged these properties and developed albumin/vaccine nanocomplexes by simple bioconjugation of Evans blue derivatives to molecular vaccines including adjuvants and peptide neoantigens. Remarkably, using endogenous albumin as a component of these nanocomplexes avoids in vitro preparation of nanomaterials, and the nanocomplexes will be assembled in vivo from modified molecular vaccines and albumin. This is extremely significant because it essentially transformed the nanoformulation into a molecular formulation which can be easily synthesized at an industrial scale, and stored on-shelf without refrigeration for a long duration. To interrogate their pharmacology, Julian exploited multiscale system pharmacoimaging including PET in animals, light sheet fluorescence microscopy in cleared lymph nodes, and super-resolution fluorescence imaging in single cells. These nanovaccines were revealed to be efficiently delivered into lymph nodes, elicited very potent T cell responses with long tumor-specific immune memory, and inhibited or eradicated tumors in multiple local and metastatic tumor models. Remarkably, when combined with immune checkpoint inhibitors, or chemotherapy, or photodynamic therapy (PDT), or radiotherapy, these nanovaccines exhibit a wide spectrum of synergy to further potentiate their abilities to inhibit tumor growth, increase the rate of complete tumor regression, and interestingly, increase the rate of abscopal effect in the cases of PDT and radiotherapy. for combination cancer immunotherapy with checkpoint inhibitors and chemotherapy (Zhu, et al., Nature Communications, 2018. Zhu, et al., in preparation.). Taking this approach of albumin/drug nanocomplexes, we have been also developing nanomedicines for small molecular immune checkpoint inhibitors IDO antagonist, chemotherapeutics, and photosensitizers (Zhang, Zhu (co-corresponding), et al., ACS Nano, 2017).

Upon joining VCU, Julian is passionate to spend his future endeavors in forging his multidisciplinary expertise to better interrogate immune-biomaterial interfaces and enable bioengineering and bioimaging tools to impact the innovation of cancer immunotherapy.

Contacts

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