Research Theme 1: Single cell technologies to discover immunotherapeutics. Immunotherapeutics including antibodies and T cells hold great promises to be next-generation treatment for cancer. However, the efforts to develop new immune-agents have been hindered by the lack of efficient tools to screen, identify and evaluate new therapeutic candidates. We have been developing single-cell technologies including particularly droplet-based systems to facilitate rapid and cost-effective discovery of immunotherapeutics. By integrating high throughput target tracking, real-time functional analysis, sorting and downstream analysis, we can dissect complex cellular heterogeneity, eliminate lengthy assay processes and identify rare high-quality clones from complex samples.

Research Theme 2: Targeting biophysical cues to study, diagnose, and treat diseases. Cells constantly interact with their surrounding niche including complex biochemical and biophysical signals. Although not appreciated historically, it has recently become evident that the physical and mechanical properties of cellular microenvironments regulate essential cell functions. We have recently demonstrated such tissue biophysical cues can be harnessed as a novel target to the development of next generation cancer treatment. Novel tools currently being developed in the laboratory to sense and target biophysical cues could lead to future diagnostics and therapies targeting aberrant tissue stiffness in conditions such as cancer and fibrotic diseases, and help to elucidate mechanobiology at a cellular level in vivo during development and cancer progression. These tools will also inform our understanding of how mechanical stimuli direct stem cell behavior and inform designing future regenerative rehabilitation strategies.

Research Theme 3: Elucidate and control the fate of transplanted stem cells. Stem cell therapies have demonstrated enormous potential for solving many tragic illnesses, diseases and tissue defects worldwide. However, the efficacy of stem cell transplantation in patients has not been well established, and recent clinical trials have produced mixed results. We attribute this lack of efficacy in part to an incomplete understanding of the fate of stem cells following their transplantation and the lack of control over cell fate. We have been developing technologies that aim to address the above-mentioned bottlenecks in stem cell therapy including: a) targeted strategies to enhance the homing and therapeutic efficacy of transplanted stem cells, b) cell-based sensors to study in vivo biology, and c) stem cell-derived exosomes as novel cell-free therapeutics and drug delivery vectors.

Research Theme 4: Clinical translation of cell therapy for regenerative medicine. Watching patients suffer from a devastating disease is enormously painful. Cell therapies including stem cells and immune cells have offered great hope for treating many tragic diseases. We are personally dedicated to accelerating these treatments to patients. Currently, we have mesenchymal stem cells (MSC) and immune cells in various stages of clinical development to treat autoimmune diseases, neurological disorders and cancer.

Research Theme 5: Biosensors and miniaturized devices for in vitro diagnostics. We have been developing rapid diagnostics to diagnose diseases at the early-stages when the intervention is most effective. We have been working on a) the global issue of antimicrobial resistance that kills hundreds of thousands of patients every year due partly to the lack of rapid diagnostics, and b) cancer detection, screening and treatment monitoring and stratification using liquid biopsies. In particular, we have recently developed the Integrated Comprehensive Droplet Digital Detection (IC 3D) technology, which introduces a new paradigm for rapid detection of low-abundance biomarkers from complex biological samples. The IC 3D technology has great potential to address a long-standing unmet need of rapid detection of bloodstream infections, antibiotic resistance and cancer.

Our laboratory is uniquely positioned at the Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, Department of Biomedical Engineering, and Department of Pharmaceutical Sciences which allows us to actively collaborate with outstanding biologists, clinicians, engineers and materials scientists to quickly translate our research findings and technologies to the clinic to benefit suffering patients. Our laboratory is located at the new Stem Cell Building which is equipped with multi-million dollar, state-of-art core facilities dedicated for training and research. Finally, we have strong partnerships with the industry and clinicians for product development, clinical trials and commercialization, which allows us to quickly translate our technologies to the bedside.

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