● Human Reproduction

We are interested in both the basic and clinical aspects of human reproduction.

Germ line genetic variation offers the raw material for human evolution, but also causes some serious genetic problems. We apply single-cell analysis to measure germ line diversity, aiming to portray this heterogenous system in a more quantitative way. Some of the biological questions we seek to answer are:

- What is the genetic variation spectrum across different germ cells?
- How does the genetic variation pattern affect mutation transmission?
- How does genetic variation affect germ cell development?

Pregnancy is a prolonged and complexed process, with so much uncertainty before the birth of the baby. The waiting is even more difficult for families with history of birth defects. We are devoted to developing diagnostic methods to better characterise the fetus from different perspectives. Based on next-generation sequencing and molecular counting, ongoing projects include the development of non-invasive methods to detect fetal inheritance of genetic variations and to detect potential placenta maldevelopment.

Finding the true disease-causing mutations in the genome is not easier than finding the needle from a haystack. There is around 0.1% difference between two random human genomes, which means disease-causing mutation is rarer than one in a million. By combining high-resolution haploid genomics and pedigree analysis, we hope to pinpoint the driver mutations behind rare inheritable diseases with higher accuracy.

● Precision Medicine

Given profound genetic variations, different patients inevitably respond differently to the same treatment. By combining quantitative genetic measurement and statistical modelling, we aim to establish the treatment prognosis prediction pipelines. Our new technologies can provide higher accuracy and efficiency for treatment selection. We are currently focusing on unveiling the genetic clue to better treatment of cardiovascular diseases and fungal infections.

● Technology Development

We have previously developed various genomics technologies, such as singel-cell and single-chromosome sequencing, to facilitate biological and medical research. Discoveries enabled by these technologies further strengthened our mind to advance along this route. We are generally interested in making measurements more accuracy and sensitive. By measuring the heterogeneity and dynamic changes of complex cell populations, our technologies are especially suitable for developmental biology and stem cell research.

Every population has to maintain a certain level of diversity to sustain unforeseeable perturbation. This is particularly true for the human immune system, at both single-cell and single-individual scales. We study the genetic diversity of the human immune system, and look for the relationship between this diversity and disease susceptibility.

Through the development from a single cell to tissue, organ, and the whole body, cells form a massive lineage system. The success of C. elegans biology has proved the importance of a clear cell lineage map. We use single-cell methods to trace cell division and apply new tools to gain insight into stem cell renew and differentiation.

Tsinghua UniversitySchool of Life SciencesCenter for Life Sciences
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