Sun Lab Research Programs - Drug Discovery and NanoMedicine
Breast Cancer Stem Cells and Therapeutics
The goal of this project is to visualize the cancer stem cells hierarchy to answer questions for how heterogeneous breast cancer cells are generated by breast cancer stem cells? How chemotherapy alters heterogeneity by changing breast cancer stem cells? Why chemotherapy can not “cure” cancer? How to identify drugs or targets to eliminate different populations of heterogeneous cancer cells in order to “cure” cancer.
Drug Optimization Alters Tissue Targeting, Efficacy and Toxicity
In drug development process, 90% drugs fail from phase I to phase III trials due to lack of efficacy (30-40%), toxicity (30%), poor drug like properties (15-20%), and lack of commercial needs (10%). The goal of this project is to investigate the failure of drug development (lack of efficacy or toxicity) is due to biological potency or tissue targeting. Why modifications in similar structures (with same target) alters tissue targeting, efficacy and toxicity? How to predict or screen tissue targeting to increase success rate of clinical trials in drug discovery? How do drugs distribute in the heterogeneous tumor tissues by MS-Imaging?
Nanotechnology for Drug Delivery
More than 90% nanomedicines failed in clinical trials. Some successful nanomedicines may have only compared combination nanomedicine with standard care to standard care alone, without comparison with free drugs (with few exceptions). The goal of this project is to investigate why most of Injectable nanomedicines failed to improve efficacy, but only alter toxicity, and how to design future nanomedicine to enhance the success rate.
Viral-Like Nanoparticle (VLN) for Non-Capsid Antigen Delivery to Activate B Cell Immunity
Various nanoparticles (NPs) have been used for delivery of small antigens, which have limited viral mimic features and are more efficacious than soluble antigens in stimulating B-cell immunity. However, these traditional NPs lack characteristics of virus “spiky capsid protein peplomer”, e.g. spiky antigen clusters on the peplomers, optimal distance between antigen clusters, and highly localized antigen density on the spike. Although virus-like features of B cell vaccine for durable B cell immunity are clinically validated using virus-like particles (VLPs) of viral capsid proteins, VLPs is not suitable for delivery of non-capsid small antigens (such as bacterial toxins, small molecules, and oncogenic peptides) since these non-capsid small antigens are not able to self-assemble to VLPs. This project is to develop virus-like nanoparticles for small antigens to activate B cell immunity against bacterial toxins, small molecules, and oncogenic peptides.
Drug Discovery to Treat P53/PTEN Deficient Triple Negative Breast Cancer
Among four types of breast cancers, triple negative breast cancer (TNBC) still lacks treatment options. Triple negative breast cancer (TNBC) exhibits high frequencies of p53 and PTEN genetic aberrations, with 84% and 35%, respectively, which is associated with metastasis, low therapeutic response, and poor prognosis. However, the concurrent p53/PTEN deficiency in TNBC is not actionable due to the lack of molecular targets. The goal of this project is to identify specific therapeutic target for drug discovery to treat P53/PTEN deficient TNBC.
Intubation and Wireless Sampling Device in GI Track For Microbiome Analysis and Drug Product Optimization
Gut microbiome has been shown to regulate immunity, cancer, and metabolic disease. The most gut microbiome is usually analyzed from feces, which is different from microbiome in small intestine. However there is lack of information for GI microbiome in small intestine due to the lack of sampling methods.
In addition, during oral drug product development, in vitro and in vivo drug dissolution needs to be optimized. However, there is lack of data and understanding of dissolution in GI tract for oral drug product development and optimization.
The goal of this project is to develop method by intubation or wireless sampling device to obtain samples from whole GI tract (stomach, duodenum, jejunum, ileum, and colon) for GI microbiome analysis and drug dissolution analysis