We developed a fully defined, clinically-compatible cell culture system that can generate purified, functional, and therapeutically effective endothelial cells (ECs) from human pluripotent stem cells (hPSCs), which include human embryonic stem cells and induced pluripotent stem cells.  We further encapsulated hPSC-ECs within the nanomatrix gel and transplanted them into experimental hindlimb ischemia. These encapsulated hPSC-ECs remained engrafted for more than 10 months in ischemic tissues, and when compared to bare hPSC-ECs, they exerted higher and prolonged neovascularization and showed better vascular regenerative capacity. 

Direct conversion or reprogramming of human postnatal cells into ECs, bypassing stem or progenitor cell status, is crucial for cell therapy, and pathophysiological investigation but has remained largely unexplored. We thus sought to directly reprogram human postnatal dermal fibroblasts (HDFs) to ECs with vasculogenic and endothelial transcription factors (TFs) and determine their vascularizing and therapeutic potential. We found that ER71/ETV2 alone is able to directly reprogram human postnatal cells to functional, mature ECs, referred to as reprogrammed ECs (rECs). These rECs could be valuable for cell therapy, disease investigation, and exploration of the reprogramming process.

Diverging patterns of gene regulation accompany inter-individual variation in immune responses, and multiple distinct pathways in immune cell types can result in either resilience or pathogenic outcomes after virus infection. Bulk-level transcriptome and single-cell multimodal profiling can reveal the immune cell landscape's distinctive functional composition, gene expression regulation, and antigen receptor repertoire, offering an unparalleled view of the disease process in patients. I will present comparative transcriptome approaches, including bulk and single-cell RNA-seq, surface proteome, and immunophenotyping (T and B cell antigen receptor) analyses of peripheral-blood cells from HIV-1 or dengue virus (DENV) infected participants. The results show consistent patterns for T and B cell subsets related to specific viruses and prior exposures. These results provide insight into the virus and host cell interaction networks modulating specific virus-related diseases. 

This lecture includes multiscale (10-2 to 10-7 m) characterization for elastic, viscoelastic, and fracture behavior of bone and cartilage, and implant systems using nanoindentation at the tissue-level, dynamic mechanical analysis (DMA) at the organ-level, bone mineralization analysis with micro-computed tomography, and clinical cone beam CT (CBCT). My lab has developed additional novel technologies to analyze tissue mineral density (TMD) distribution and characteristics including static and dynamic elastic, viscoelastic, and plastic mechanical properties at the multiscale of bone and implants in the same individual. More than 50 parameters are determined. The subject of research can be extending in multiscale characterization of general materials.

The filamentous fungus Aspergillus oryzae is a GRAS (Generally Recognized as Safe) organism that has been used for thousands of years to produce various foods, including Doen-Jang, Korean traditional liquors, miso, and sake. Growing this food-grade A. oryzae fungus in different proprietary culture media made of various food ingredients led to the development of two types of novel bioproducts, termed D-Tox™ and Natural Preservative™ (NP™). D-Tox™ is an edible culture fermentate that can effectively degrade aflatoxins (Afs; the most potent carcinogen found in nature) within various foods, herbal medicines, and oil. AF detoxification involves opening the AF lactone ring followed by decarboxylation and further fragmentation of the toxin into nontoxic substances. NP™ products are also edible food fermentates that can effectively control a broad range of food-borne pathogenic bacteria, at least 10 different MRSA strains, and the human pathogenic fungi Aspergillus fumigatus and Candida species. Due to the significant potential of these bioproducts to safeguard global food safety and serve as novel antimicrobials, various US, Korean, and international patent applications have been filed, and several industry partners are working with us.   

In 2012, the U.S. Food and Drug Administration (FDA) released a guidance document entitled Guidance for Industry: Oversight of Clinical Investigations – A Risk-based Approach to Monitoring and the European Medicines Agency (EMA) released Reflection Paper on Risk Based Quality Management in Clinical Trials. Regulatory agencies are expecting the pharmaceutical companies to take risk-based approaches in various clinical trial-related activities including monitoring. Centralized monitoring is the way to enable risk based monitoring and meet the regulatory and industry expectations. The value of Central monitoring and how this helps enhancing data quality in clinical trials will be presented.

Drug discovery is time-consuming and expensive, largely owing to the substantial costs and long development period. It takes on average of 2.6 billion dollars and over 10 years to bring a new drug to market. Artificial Intelligence (AI) is becoming more widely adopted in the pharmaceutical industry to enhance drug discovery efficiency. At the preclinical stage, AI helps to reduce the development time and cost significantly by removing the compounds with undesirable potency before the synthesis and biological test. More importantly, AI can suggest a new compound possibly with desirable potency, selectivity, and PK/PD properties by virtually exploring the expanded chemical space. The key to success in AI-driven drug discovery depends on how well it is integrated into the biology and chemistry teams of drug discovery. Our AI drug discovery technology and integrated drug discovery platform will be introduced with case studies of how we solved challenging problems with AI.