(6hj) Priming the Innate Immunity Using Nanomedicine

Research Interests: The innate immune system is implicated in an enormous number of disease processes such as malignancy and inflammation that affects millions of people around the world. Take cancer as an example, most cancer patients still do not benefit from current immunotherapeutic approaches that focused on enhancing T-cell responses, due to the low response rate, immunological toxicities, and expensive price. Targeting innate immunity in cancer has the potential to enhance current T-cells based immunotherapeutic approaches by inducing multilayered immune response. However, precise modulation of innate immunity is still a CHALLENGE, as therapies can often be a double-edged sword and cause either immune suppression in the whole body or serious autoimmune/non-specific inflammation. Nanotherapeutic approaches provide the opportunity to induce a precise immune response and reduce the immunological toxicities associated with current approaches. However, the clinical translation of nanotherapeutics requires thorough understanding of both disease pathology and clinical practice.

The OVERARCHING GOAL of my research is to establish a fundamental understanding of the nanomedicine design and their interaction with the immune system, with a focus on cancer and inflammatory diseases. There are two major arms in my research program: (1) using ex vivo and in vivo models to understand the interaction between nanomedicine and the tissue microenvironment at the disease foci; and (2) using this information to develop nanomedicine that precisely modulate the immune response. The ULTIMATE GOAL of my research is to translate nanomedicine into clinics. My lab will leverage the power of synthetic chemistry and materials science in the design of novel nano-devices for mRNA & drug delivery. We will also apply state-of-the-art molecular biology and immunology tools (e.g. genome sequencing, multicolor flow-cytometry, fluorescence-based imaging technique) to understand the interaction between nanomedicine and the immune microenvironment at the disease foci. Teaching Interests: this multidisciplinary work will provide training for engineering students, immunology students and clinical fellows. Specifically, I am interested in teaching these students how to solve multi-faceted challenges by integrating knowledge across boundaries.

My knowledge in engineering, immunology, and my experience of working closely with the clinical side has placed me in a unique position to establish an interdisciplinary research program that integrates training in engineering nanoparticle platforms with an understanding of nanoparticles formulation, analytical chemistry, immunology, cancer biology, and translational research. During my doctoral work with Dr. Kannan Rangaramanujam, I developed dendrimer-based nanomedicine for central nervous system diseases, now a patented technology. Through collaborating with neuroscientist, neurosurgeons, we built the guiding principles for designing nanomedicine that efficiently crosses biological barriers and targets neuroinflammation. My postdoctoral training with Dr. Matthias Stephan at Program in Immunology, Fred Hutchinson Cancer Research Center built my foundation in immunology and cancer biology, leading to experience in understanding immunotherapy, gene therapy, as well as developing clinically relevant tumor models. Based on my combined doctoral and postdoctoral work, I have published 19 peer-reviewed publications, 4 international patents, and was awarded the Basic Research Award by American Brain Tumor Association, an award that provides $100K over 2 years of transitioning from postdoctoral level training to a faculty position.

Education

Ph.D., 2016, Johns Hopkins University, Materials Science and Engineering

B.S., 2010, Donghua University, Materials Science and Engineering

Selected Publications

• Zhang F, Parayath N, Coon M, Stephan SB, Ene CI, Holland EC, Stephan MT. Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nature Communication. accepted.
• Zhang F, Stephan SB, Ene CI, Smith TT, Holland E, Stephan MT. Nanoparticles that reshape the tumor milieu create a therapeutic window for effective T cell therapy in solid malignancies. Cancer research. 2018. Cancer Research.2018 **Selected Cover Image
• Zhang F, Nance E, Alnasser Y, Kannan RM, Kannan S. Microglia migration and interactions with dendrimer in brain in the presence of neuroinflammation. Journal of Neuroinflammation. 2016 Mar 22;13(1):65.
• Zhang F*, Mastorakos P*, Mishra M, Mangraviti A, Hwang L, Zhou J, Hanes J, Brem H, Olivi A, Tyler B, Kannan RM. PAMAM Dendrimer Biodistribution in Glioblastoma and Intrinsic Targeting of Tumor Associated Macrophages. Biomaterials. 2015. 52:507-16.