Our Work

The rapid advancement of sequencing technologies over the last two decades has delivered unprecedented insights into the biology of the human genome. We are passionate about genomic technology innovation, equipped with an established large-scale sequencing center, and have scientific track records in chromatin biology. We have conceptualized the pair-end-ditag (PET) sequencing strategy and made concerted efforts in the maturation of long-read technologies. We currently demonstrate their immense utilities in characterizing mammalian genome structures and function through the following projects.

Characterizing the Extrachromosomal DNA Chromatin Topology in Enhancing Transcription and Tumor Fitness

Cancer cells containing extrachromosomal DNA circles are often aggressive and have poor patient outcome, so understanding how these DNA circles affect cancer cell behavior is critically important to devise new strategies for effective treatment. This project will employ new technologies in ultralong sequencing of genomic DNA and chromatin interaction analyses to determine the complete composition of these DNA circles and thereby reveal 1) how ecDNA interacts with chromosomal genes that promote cancer progression, and 2) how ecDNA evolves in response to treatment with anti-cancer drugs. The findings of this research will shed much-needed light on the role of extrachromosomal DNA circles in cancer, while also providing cancer researchers with advanced approaches that will enable them to study extrachromosomal DNA circles across multiple cancer types.

Single Cell and Single Molecule Technologies for Multiplex Chromatin Interaction Analysis

Mammalian genome DNA in the cell nucleus is extensively folded to form a complex three-dimensional (3D) chromatin organization, comprising complex and multivalent interplays of chromatin interactions involving DNA, RNA and protein. The 3D genome is arranged to facilitate multiple functional interactions that ultimately serve to regulate gene expression within a cell. Our current understanding is limited and understanding these complex functional interactions and their variations will be necessary not only for advancing fundamental biological knowledge, but also for providing novel insights into human disease that could lead to new treatment paradigms.

We seek to develop a set of single cell and single molecule techniques for studying multiple, complex chromatin interactions involving protein and RNA regulatory factors within the 3D genome organization. The development of these advanced single-cell chromatin technologies and tools will enable unprecedented exploration of chromatin interaction biology and advance our understanding of chromatin topology and genome regulatory functions.

Advancing long-read sequencing for structural variation characterization in human genome

Genomic technologies have made personalized medicine a reality. Our ability to read genomes and epigenomes with precision, scale and efficiency is the driving force to advance our understanding in genome structures and function. We are in the beginning of the era of long-read sequencing with matured platforms of high accuracy, reliability, and output. By participating in NIH precision medicine programs including All of Us, we aim to build state-of-the-art long-read technology and analysis platforms to enable the detection of complex somatic variants. We plan to determine their function significance in transcription and disease mechanisms.