Our Research Interests
We focused on the use of synthetic biology approach to investigate biological pattern/structure formation, to develop vaccines against cancer cells and infectious diseases, and to create novel cancer treatment.
Other major research interest is to investigate the roles of intracellular transportation in development, cellular function and diseases.
Use of Synthetic Biology
Pattern Formation
Synthetic Biology refers to the design and fabrication of biological components and systems that do not already exist in the natural world; and the re-design and fabrication of existing biological systems for useful purpose. Synthetic biology plays a significant role in understanding and manipulating pattern formation in various biological systems. These include uses such as modeling biological systems, engineering organism, cellular communication, developmental biology studies, and regenerative medicine.
The JDH laboratory is aiming to design and fabricate artificial biological parts, devices and circuits to control pattern formation by consgtructing models of genetuic circuits that can mimic natural systems, aiding in the study of how patterns arise in organism.
Vaccine Design
Antigenic Field Theory and Vaccines against Viruses
Current COVID-19 vaccines are highly effective against symptomatic disease, but repeated booster doses using vaccines based on the ancestral strain offer limited additional protection against SARS-CoV-2 variants of concern (VOCs). To address this, we used "antigenic distance" to in silico select optimized booster vaccine seed strains effective against both current and future VOCs. Based on research and analysis of immune escape of SARS-CoV-2 virus, we constructed an "antigen distance" model using existing neutralization and sequencing data. This model measured the degree of immune escape between different mutant strains based on the neutralizing abilities of human sera against various strains. Based on the "antigenic distance", we can generate a region in which each point (variant) has a vaccine efficacy associated with it. In the Discussion of the paper, the researchers proposed a new concept called the "antigen field" to better understand and quantify the interactions (immune responses) between the human immune system and foreign antigens. This concept is similar to an "electric field" and refers to the fundamental interactions diffused within the immune space. Infection or administration of a specific antigen generates an "antigen field." After its activation, this antigen field can "repel" subsequent antigens attempting to enter the same field or antigens that are in close proximity to the initial antigen in terms of antigenic distance. The proposed "antigenic field" concept opens new avenues for understanding the immune system's interaction with foreign antigens, potentially influencing future vaccine and immunotherapy development.
Vaccine Design
Vaccines for Antimicrobial Resistance (AMR)
The global challenge of antimicrobial resistance (AMR) necessitates the development of novel strategies and vaccines to effectively combat bacterial infections. To achieve this goal, we used multiple strategies including synthetic-biologically engineered live attenuated vaccines and rationally designed bacterial outer membrane vesicles (OMVs). For live attenuated vaccines, it is critical to engineer bacteria by weakening their virulence but keeping the protective immunity. While for OMVs, it is vital to include and display effective antigens properly to induce protective immunity. We rationally deigned vaccines against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae.
Bacteria-based Cancer Vaccines
Salmonella is a Gram-negative species that generally causes self-limiting gastroenteritis in humans. We rationally designed and engineered Salmonella that can selectively colonize tumors, where they can proliferate and exert direct oncolytic effects as well as stimulating the immune system.
Development of Aging Vaccine
An aging vaccine, often referred to as a senolytic or anti-aging vaccine, aims to combat the biological processes associated with aging and age-related diseases. Recent scientific findings suggest that these vaccines target senescent cells, which are damaged cells that accumulate with age and contribute to various age-related health issues.
Senolytic therapies focus on eliminating senscent cells-cells that have stopped dividing and contribute to aging and age-related diseases. The mechanism includes:-
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Identification of senescent cells - senscent cells often exhibit distinctive markers, such as altered cell surface proteins and specific secretory profiles leading to increased inflammation. Such markers have been identified to help identify senescent cells in tissues.
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Selective targeting - senolytics are designed to selectively target and eliminate these damaged cells while sparing healthy cells. This is achieved using various compounds including drug combinations, and natural compounds.
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Immune response activation - senescent cells release inflammatory cytokines and factors that can trigger an immune response.Senolytic therapies may enahnce the immune system's ability to identify and clear these problematic cells.
Our team focus on the study of senolytics therapy and our objectives are:-
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to develop protein X-based senolytic peptide vaccines
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to detect whether the vaccines can elicit a specific T cell response in vitro
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to explore the function in aging accelerated mice models with vaccination
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to examine whether the vaccines could extend the healthy lifespan of naturally aging mice
In our findings, it is showed that eliminating senescent cells by protein X-based peptide vaccine can improve healthspan and lifespan in animal models.
It is shown that aging vaccines can help to prevent age-related diseases, enhance quality of life, increase lifespan while maintaining health, and boost immunity.
Intracellular Transportation
Our major research interest is in the mechanism of intracellular transportation and its roles in development, neuronal function and genetic diseases. Within the cell, a variety of cellular components are moved to specific sites at specific times. The intracellular transportation processes are essential not only for housekeeping purpose but also for specialized cellular functions, such as the transport of synaptic vesicles. Intracellular transportation is carried out over two major cellular networks, the microtubule and actin networks. Microtubule motors include the kinesin and dynein families of proteins while actin motors are the myosin family of proteins. Current research suggests that the microtubule network is used for transport over long distances while the actin network is used for short-range delivery in animal cells. Disruption of these processes result in genetic diseases. For example, mutation in myosin-VA results in human Griscelli disease characterized by pigment dilution, immunodeficiency, neurological defect and cognitive disorder. Mutations in other motor molecules result in many other diseases such as heart diseases and deafness.
Our previous work demonstrated that myosin-VA can interact directly with the ubiquitously expressed kinesin, implying that the two transportation systems are at least partially coordinated through their motor molecules. The major interest of our group is to use transgenic and knockout mice to study the functions of kinesins in chondrocytes, neurons, and other cell types.
