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My research has been focusing on enhancing the complexity of reconstructed skin models through i substitution and diversification of non-animal derived scaffold materials, ii inclusion of additional cells compared to traditional models and iii generation of follicular structures, all using 3D bioprinting.
This technology allows the precise placement of the bioinks containing scaffold components and cells at appropriate locations within the 3D skin tissue.
This project can help in the development of the next generation of skin models for screening of chemical compounds as well as clinically superior skin grafts. It has been reported that nearly one out of every 20 women using antidepressants three months before becoming pregnant or during the pregnancy. Deciding to continue or stop using antidepressants during pregnancy is one of the hardest decisions a woman must make. There has been a long ongoing debate about whether the use of antidepressants during pregnancy is associated with an increased risk of congenital defects.
The embryotoxicity studies for preclinical drug development have been suffering from limited human studies and short of standardized assays to screen and classify the drug embryotoxicity before clinical trials. My research career focuses on the development of human-specific embryotoxicity testing model system based on human induced pluripotent stem cells hiPSCs to replace the animal-based studies, and this screening system can provide more precise assessment of human-specific drug effect on fetus development.
My project for this Lush Prize focuses on the establishment and validation of a developing heart model that recapitulates early human heart formation in a tissue culture dish. Using this heart model, I aim to establish a risk classification system of safe pregnancy medication for fetus heath, and further rank the embryotoxicity risk level of current available antidepressants in market. Thousands of natural and synthetic chemicals, derived from agricultural, industrial and medical applications, are responsible for a broad spectrum of adverse health effects on humans and wildlife.
Exposure to endocrine disrupting chemicals EDCs can dysregulate the physiological functioning of the endocrine system by mimicking the interaction of natural hormones at the receptor level and altering synthesis, transport, and metabolism pathways.
The continuous advances in information technology and life sciences led to a deeper understanding of the biological pathways and modes of action of xenobiotics. I use the combination of these fields to develop high-accuracy quantitative structure-activity relationship QSAR models based on cheminformatic tools to predict the toxicity of chemicals.
In this aim, I led two international consortiums to predict potential estrogenic and androgenic toxicity in partnership with the National Center of Computational Toxicology NCCT at the U. EPA and several renowned research groups. By saving uncountable number of animal lives, time and cost, these predictive in silico methods are more and more accepted within the scientific community and regulators as alternatives to classical testing methods that are hopefully turning obsolete.
In addition to presenting the same prediction as the standard DPRA, mDPRA also becomes more accessible, for example, in developing countries, where animal testing continues to be widely used.
Another modification of standard DPRA is proposed by adding solar exposure step, namely photo-mDPRA, thereby making the technique capable of characterizing photosensitizers.
Moreover, only one technique can be applied for investigating two endpoints, sensitization and photosensitization. In particular, photosensitization is a very important endpoint to be investigated in products used in countries with high solar irradiation. Development of a dysmyelination test to study developmental neurotoxoicity of environmental chemicals in a human brain microphysiological system.
The scientific community has shown that during pregnancy the fetus passes through one of the most vulnerable stages of development with regards to exposure to chemicals and other environmental factors. The increase in developmental disorders such as autism has fueled concerns that they may be caused by environmental exposures to unknown toxicants.
In order to prevent these possible exposures, chemicals are subjected to testing, but determining neurotoxic effects of chemicals on brain development is very expensive and require a large number of animals. In addition, humans and rodents differ considerably, making it difficult to study and predict the effects of the vast number of chemicals in the market. Developing cheaper and more human-relevant test to classify chemicals its key to preventing developmental disorders.
Numerous efforts in the area of developmental neurotoxicity have suggested a battery of human in vitro test that cover the critical steps during fetal development.
Over the last five years, our laboratory has developed an in vitro human brain model. One of the key features of our model is its ability to recapitulate one of the important processes of brain development myelination , which is more difficult to simulate in vitro.
Preliminary results suggest we can use this myelination process to study potentially problematic chemicals in fetal development. In this project, we aim to prove that our model could serve as a novel tool for classifying developmental neurotoxicants, while being more humane, less expensive, and requiring fewer animals. Toxicity pathway-based assessment of chemical-induced mitochondrial toxicity using in vitro assays and computational modeling. Toxicity tests are undergoing a great and rapid transformation from traditional animal tests to in vitro assays and other non-animal approaches such as computational modeling.
As one of the pioneer groups on toxicological alternatives in China, over the last few years my colleagues and I have been working on in vitro assessment of chemical-induced mitochondrial toxicity using the strategy and technologies suggested by TT21C report, which is recognized as a milestone report in toxicology.
We applied a series of in vitro assays like high content screening and computational modeling approach, all of which are completely animal free, but provide useful and important information with high sensitivity. We have made significant progress and obtained many interesting and promising findings on toxicity pathway and mechanism-based risk assessment. Thrombosis is the formation of obstructive blood clots within blood vessels, which may block blood flow to vital organs.
It is a common cause of ischemic heart disease, myocardial infarctions, and stroke, which collectively cause over one in four deaths worldwide. Thrombosis is typically studied using either in vitro 2D vascular cell and tissue cultures or in vivo animal models, both of which have limitations. Cell and tissue cultures fail to replicate the complex vessel geometries and blood flow dynamics that contribute to thrombosis, and animal models may not be representative of human physiology.
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