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Jiangbing Zhou, PhD

Professor of Neurosurgery

Research Summary

Our research group focuses on developing translational nanomedicine, gene therapy, and stem cell therapy for treatment of neurological disorders through a unique combination of biology, material science,and engineering.

Extensive Research Description

Non-viral genome medicine. Our initial endeavors concentrated on engineering nanoparticles (NPs) to enhance encapsulation, cell penetration, and escape from endosomes (Biomaterials, 2012, 2014). Although promising, this approach's complexity posed limitations. To streamline our formulation, we innovated a chemistry technique to synthesize a novel class of terpolymers and their derivative single-component NPs for gene delivery (Nature Materials, 2012; ACS Nano, 2016; Advanced Science, 2020). Further strides included the creation of liposome-templated hydrogel nanoparticles to facilitate efficient CRISPR/Cas9 delivery to the brain (Adv Funct Mater, 2017). In a more recent breakthrough as part of the NIH SCGE program (Nature, 2021), we pioneered a chemical engineering approach that circumvents NPs for delivering genome editing machinery to the brain, resulting in brain-wide neuronal editing. This innovation has been applied to treat a varity of neurogenetic diseases. Presently, the system is undergoing preparation for IND-enabling studies and clinical translation. Building on the success, our current focus centers on developing the next generation of nanoparticles while also pursuing NP-free methodologies for further improved delivery efficiency as well as tissue-specific targeting.

Drug delivery to the brain. Efficient drug delivery to the brain remains a formidable challenge due to the presence of the blood-brain barrier (BBB). To surmount this delivery challenge, we developed brain-penetrating NPs specifically tailored for locoregional drug delivery to the brain, circumventing the BBB (PNAS, 2013), as well as brain-seeking NPs achieved through either intricate multiple-component engineering or a more streamlined single-component design for non-invasive drug delivery to the brain, traversing the BBB (ACS Nano, 2016, 2018; Adv Funct Mater. 2017, 2020; Nature Cell Biology. 2020; Advanced Materials. 2017; Nature Biomedical Engineering. 2020). Leveraging the success of these breakthroughs, our ongoing focus centers on development the next generation of NPs with simplified formulations, as well as the exploration of NP-free methodologies. These innovative strategies hold the potential to revolutionize systemic drug delivery to the brain, and, thus, may lead to a transformative impact on the treatment landscape of various neurological diseases.

Biology of brain cancer. I was among the first pioneering group studying cancer stem cells (CSCs) in solid tumors. My early-stage work provided substantial evidence about the importance of CSCs in cancer treatment and suggested directions in achieving their preferential elimination (PNAS, 2007; BCRT, 2008, 2009). Leveraging my collaboration with esteemed neurosurgeon colleagues, we have recently established a comprehensive array of resources dedicated to brain cancer research. Building on these resources, we performed a genome-wide RNAi screen and identified several novel genes, which regulate BSCS differentiation and migration, and completed a large-scale drug screen on multiple BCSCs (Advanced Science. 2019, Neuro-Oncology, 2022; Nature Communications. 2022). Currently, our primary focus revolves around in-depth investigations of these lead candidate genes and identified drugs. Our overarching objective is to unravel their therapeutic potential, with the ultimate goal of develop novel approaches for the treatment of brain cancer.

Nanomaterials for oral drug delivery. With its convenience and high patient compliance, oral drug delivery remains a preferred method for many patients. In our pursuit of innovative approaches, we took an unconventional route by exploring nature-derived nanomaterials. This led us to discover a group of small molecules forming supramolecular NPs, some of which show efficient drug encapsulation and gastrointestinal penetration. Inspired by this, we developed novel polymeric materials optimized for oral drug delivery. These materials have proven capable of facilitating oral delivery of various therapeutics, including protein drugs like insulin and antibodies, offering new avenues for disease treatment.


Research Interests

Alzheimer Disease; Biocompatible Materials; Biomedical Engineering; Brain Injuries; Brain Neoplasms; Glioblastoma; Genetic Therapy; Drug Delivery Systems; Angelman Syndrome; Stroke; Nanomedicine; Nanoparticles; Cell- and Tissue-Based Therapy

Selected Publications