(6kw) Engineering Biomimetic Materials and Cells for Diagnostic and Therapeutic Applications

Nature represents the largest reservoir from which people can learn to better understand biological processes and design strategies to interfere with these processes. My career objective is to apply concepts from nature to rationally engineer bioinspired and biomimetic materials and cells to interface with biology and tackle grand challenges in medicine. Especially, my research focuses on making biomimetic materials and engineered cells as effective approaches to both diagnose and treat diseases. My goal is to run a multidisciplinary research group that mainly focuses on two broad research areas. 1) Engineer biomimetic nanomaterials for immunoengineering and immunomodulation. In this area, I envision that engineering nanomaterials to mimic and interfere immunological processes can achieve systemic or local immunomodulation for disease treatment. One particular interest is to design the next-generation biomimetic nanovaccines to modulate the immune response for treating diseases like addiction to abusive drugs and cancers. 2) Engineer circulating blood cells for the diagnosis and treatment of diseases. In this area, one particular interest is to specifically deliver therapeutics, imaging agents, and nanoparticles to target sites by hitchhiking them to circulating blood cells. Especially, erythrocytes, platelet, and monocytes are three main cell types I am especially interested in. Another particular interest is to surface engineer cells to make them perform like another cell type to solve unmet clinical needs.

PhD Dissertation: “Biomimetic nanomaterials for designing the next-generation vaccines against abusive-drugs and enhancing cancer drug delivery”

Advisor: Chenming Zhang, Ph.D., Department of Biological Systems Engineering, Virginia Tech

Postdoctoral Project: “Cell-, ionic liquid-, and nanocarrier-based strategies for drug delivery”

Advisor: Samir Mitragotri, Ph.D., John A. Paulson School of Engineering and Applied Sciences, Wyss Institute of Biologically Inspired Engineering, Harvard University

Research Experience:

My background as a chemical/biomedical engineer, along with my training in biomaterials, immunology and drug delivery, equipped me with skills to contribute substantial progress in the field. Working with Chenming Zhang during my Ph.D. at Virginia Tech, I worked on engineering the next-generation biomimetic nicotine nanovaccines for immunotherapy against nicotine addiction. Inspired from viruses that are highly immunogenic, we designed hybrid nanoparticle-based nicotine nanovaccines that mimic the structure of viruses. This biomimetic nicotine nanovaccine outperformed conventional conjugate nicotine vaccines that have failed in clinical trials. In addition, by conducting systemic mechanistic studies, we elucidated how fine tuning each component of a nanovaccine could modulate its immunological efficacy. Working with Samir Mitragotri during my postdoc training at Harvard University, I learned how to tackle significant biological barriers for effective drug delivery using biomimetic cell- and material-based approaches. One aspect of my postdoc work has been focused on engineering erythrocytes for drug delivery and immunomodulation. In one direction, we engineered an erythrocyte hitchhiking approach to achieve systemic administration enabled local drug delivery. Based on this technology, we developed Erythrocyte Leveraged Chemotherapy (ELeCT) that could enable conventional chemotherapy for effective treatment of lung metastasis and Erythrocyte Anchored Systemic Nano-immunotherapy (EASY) that could restore local tumor immune microenvironments at the metastatic sites. In another direction, we engineered an erythrocyte hitchhiking approach for systemic immunomodulation. The second aspect of my postdoc work has been focused on tackling the skin barrier using ionic liquid-based materials. Specifically, we engineered ionic liquids that could enhance transdermal delivery of a range of immunomodulatory agents for skin immunomodulation.

Teaching Interests:

I believe that rigorous education forms the basis for innovative research and thus teaching is one of the central part of a great research university. My teaching experience includes serving as a Teaching Assistant in 4 courses. In this capacity, my responsibilities entailed developing and delivering review lectures, grading all assignments, leading class discussions, designing and supervising laboratory experiments, and meeting with students individually. In addition, I have mentored and trained > 20 undergraduate, master students, or Ph.D. students. I am prepared to teach both in chemical/biomedical engineering, my area of research expertise, and in a wide range of courses in bioengineering and pharmaceutics, at the introductory, intermediate, and advanced levels. I especially enjoy mentoring students in active project-based learning in medium classes, and I would welcome the opportunity to develop new courses according to departmental needs, especially on advanced drug delivery technologies.

Education:

Ph.D., 2017, Biological Systems Engineering (Biomolecular Engineering concentration), Virginia Tech

B.S., 2013, Biochemical Engineering, East China University of Science and Technology

Selected Publications (see my C.V. for a complete publication record):

Zhao Z., Ukidve A., Gao Y., Kim J., Mitragotri S. Erythrocyte Leveraged Chemotherapy (ELeCt): Nanoparticle assembly on erythrocyte surface to combat lung metastasis. Science Advances 2019.

Zhao Z., Ukidve A., Krishnan V., Fehnel A., Pan D., Gao Y., Kim J., Evans M., Guo J., Mitragotri S. Erythrocyte Anchored Systemic Nano-immunotherapy for restoring local tumor immune microenviroment. Nature Nanotechnology, in revision.

Zhao Z., Harris B., Hu Y., Harmon T., Pentel P., Ehrich M., Zhang C. Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction. Biomaterials 2018.

Zhao Z., Powers K., Hu Y., Raleigh M., Pentel P., Zhang C. Engineering of a hybrid nanoparticle-based nicotine nanovaccine as a next-generation immunotherapeutic strategy against nicotine addiction: A focus on hapten density. Biomaterials 2017.

Zhao Z., Hu Y., Harmon T., Pentel P., Ehrich M., Zhang C. Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization. Biomaterials 2017.

Zhao Z., Hu Y., Hoerle R., Devine M., Raleigh M, Pentel P., Zhang C. A nanoparticle-based nicotine vaccine and the influence of particle size on its immunogenicity and efficacy. Nanomedicine: Nanotechnology, Biology and Medicine 2017.

Zhao Z., Ukidve A., Krishnan V., Mitragotri S. Effect of physicochemical and surface properties on in vivo fate of drug nanocarriers. Advanced Drug Delivery Reviews 2019.

Zhao Z., Ukidve A., Dasgupta A., Mitragotri S. Transdermal immunomodulation: Principles, advances and perspectives. Advanced Drug Delivery Reviews 2018.