(4dj) Programming Bioresponsive Nanobiotechnology for Disease Profiling and Precision Medicine

Integration of precision diagnostics with personalized therapies provides a revolutionary solution to clinical management of cancer. Tissue-environmental features from tumor progression, metastasis to immune infiltration in cancer harbor numerous novel biomarkers and therapeutic opportunities for advancing precision diagnostics and medicine in oncology. I will develop next-generation programmable molecular diagnostics (e.g., nanosensors, biosensors, imaging probes) that harness microenvironment-dependent activation mechanisms for biomarker profiling, early detection, longitudinal monitoring and response prediction of different therapies. By leveraging these discovered microenvironmental features, I will engineer highly modular bio-responsive nanomaterials that enable precise drug (e.g., gene editors, protein-based therapeutics) delivery at multiscale levels with tissues, diseases, cellular, and/or subcellular resolutions. I will also pursue for translating these technologies in collaboration with medical scientists and clinicians.

Collectively, my research will advance precision health through integrating noninvasive approaches for biomarker identification, early detection, timely drug intervention and monitoring in a personalized and point-of-care manner in the context of cancer, chronic pulmonary disorders and neurodegenerative diseases.

Teaching Interests

I believe the science is real, reproducible, and rigorous and recognize that we acheive the most when working together as a team. Therefore, I will foster a diverse, collaborative, independent and interdisciplinary training environment for professional development, with postdocs and students from engineering, chemistry, biology, and pharmaceutical science. As a chemical and biomedical engineer by training, I am excited to teach core courses in areas include transport, thermodynamics, biomaterials and nanotechnology. I am also very enthusiastic to develop elective courses related to my research interests in drug delivery, biomolecular engineering, nanotechnology, cancer and systems biology. As a faculty, I am strongly committed to promoting gender and racial equity STEM, and mentor diverse and underrepresented groups of students. I will leverage all my resources and opportunities to engage in DEI service, outreach activity, and education of next-generation scientists and engineers.

Previous Research Experiences

I am a chemical and biomolecular engineer to understand and harness disease-specific microenvironment for early detection and precision therapeutic intervention. As a graduate researcher, I developed inhalable a class of stimuli-responsive nanoparticles for chemotherapy and gene therapy of lung cancer. These nanotherapeutics administered through a pulmonary route enable robust efficacy against lung cancer and promise to decrease off-target toxicity. As a postdoctoral fellow, I engineered biocompatible and clinically translatable nanoparticles that allow focused ultrasound-induced uncaging of neuromodulators for noninvasive transcranial neuromodulation and glymphatic transport modulation. I showed that the neuromodulatory effect of ultrasonic drug uncaging is limited spatially and temporally by the size of the ultrasound focus and the sonication timing. This approach allows robust and precise perturbation of brain activity at any point of the brain. At MIT, I developed and translated protease-activatable nanosensors that enable detection and monitoring of lung cancer with upregulated proteases via urinary readouts, and adapted the activity-based diagnostics to a point-of-care kit comprising inhalable nanosensors and lateral flow assay that can yield testing results at de-centralized settings. Such modifications to the technology would make feasible the potential large-scale clinical deployment in resource limited settings to detect growing noncommunicable diseases. Though this concept was originally intended to be applied to diagnosis, I also recognized its significant therapeutic potentials, and quickly extended the “conditional” concept into interventional oncology. I engineered a library of conditional flipid-based nanovesicles to enable highly on-target delivery of drugs and biologics, more importantly, to efficiently bypass endosomal trapping for subcellular delivery of vulnerable therapeutics, including genetic materials.