Embedded Files
Drug Repurposing and Computer-aided Drug Design [CADD]
Computer-Aided Drug Design (CADD) exploits state-of-the-art technologies to speed up the drug development process very efficiently. Recently, we have been successfully established the pipeline of motif-guided drug screening and drug carrier peptide design using CADD with appropriate in vitro & in vivo approaches. The pipeline focuses on the development and optimization of well-balanced methods with computational sequence/structure-based design and enzyme-based, molecular cell biology experiment targets to the drug resistance, abnormal protein aggregation, and drug delivery system. The final goal of research interest is to design and develop concurrent combinational therapies that take into account structural precise mechanisms of certain diseases and pharmacokinetics.
Additionally, our repurposing strategy takes advantage of all known information regarding pharmacokinetics, toxicity, and brain penetration of each selected compound. This allows us to identify lead compounds able to cross the blood-brain barrier, serving as potential candidates for further drug development which can rapidly advance through animal and pre-clinical trials. This work will set a foundation for future drug design and lead discovery studies.
Fluorescence-based Human and Bacteria Cell Assay
The Tau RD P301S FRET Biosensor cells stably expressing the repeat domain of Tau with the P301S mutation conjugated to either the cyan fluorescent protein (CFP) or the yellow fluorescent protein (YFP). In the fluorescence-based cell research, we assess their impact on tau seeding using the HEK293T tau biosensor cell line developed for monitoring and quantifying intracellular tau aggregation and seeding. Expressing tau RD containing the disease-associated P301S substitution fused to either CFP or YFP, the biosensor cells produce a FRET signal upon aggregation of tau, which can be quantified using flow cytometry.
The bacterial-related assay is difficult to measure using classical techniques due to the small cell size and its colony formation. Fluorescence (GFP/RFP)-based bacterial assays can be employed to analyze the growth of Gram-negative bacteria and host cell adhesion availability. This approach has several important advantages compared with traditional assays, such as visible data, short time of measurements, high sensitivity, and reproducibility with single-cell flow cytometry.
Protein Crystallization Study
Structure-based drug design is becoming an essential tool for faster and more cost-efficient lead discovery relative to the traditional method. This structure-based drug design relies on knowledge of the three-dimensional structure of the biological target obtained through methods such as x-ray crystallography or NMR spectroscopy. Using the structure of the biological target, candidate drugs that are predicted to bind with high affinity and selectivity to the target may be designed using interactive graphics and the intuition of a medicinal chemist.
Our X-ray crystallography approach offers the unparalleled advantage of a clear inhibitor interaction mechanism relating the experimental data to the protein-ligand binding model.
Proteomics Approach
Proteomics involves using highly complex protein screening technology for biological understanding on a wide-scale level. This information can then provide an understanding of the fundamental biological mechanisms underlying the origin of drug resistance, neurodegenerative diseases.
This approach allows a selected group of proteins to be studied and characterized and can provide important information about protein signaling, disease mechanisms, or protein-drug interactions.
Proteomics is used to determine functional protein networks that exist at the level of the cell, tissue, or whole organism, but currently, in our laboratory, it is mainly used to detect specific protein expression patterns that induce drug resistance at a given time in response to a specific stimulus.
Skin Wound Model in vivo Test
ESKAPE pathogen has become a problematic, nosocomial species of bacteria responsible for various types of infections ranging in severity from urinary tract infection to skin and soft tissue infections, as well as ventilator-associated pneumonia. Implicating ESKAPE as the cause of these wound infections is the result of the increase in the number of MDR infections on the whole. There is an urgent need to develop effective strategies to prevent wound infection and promote wound healing after injury. Our laboratory currently established an animal model to evaluate novel combination therapy regimens using 1) ESKAPE pathogens transformed with a fluorescent protein (GFP/RFP) and 2) beta-lactamase protein-expressing pathogens.
SHIN Lab is affiliated with the College of Pharmacy at NEOMED.
Postal Address: 4209 state route 44, Rootstown, Ohio, 44272 USA
Page updated
Google Sites
Report abuse