ZZ-lab is fascinated by the biology of transposon and circular DNA.
Transposons can mobilize to re-write the genome information. They have thrived in almost all organisms throughout evolution. Increasing evidence suggests that hosts have domesticated these genomic parasites to maintain their own development and functions. Nevertheless, transposons still represent a potentially explosive source of genomic instability that can cause animal sterility and disease, and potentially drive aging. Therefore, the interaction between hosts and transposons represents a fundamental genetic conflict that shapes numerous biological processes, such as gametogenesis and carcinogenesis. Remarkably, despite the importance of this arms race, little is known about the mechanisms that maintain it and how they might be corrupted to cause disease. Our lab has been captivated by this genetic conflict. Our research investigates the impact and regulation of transposons, aiming to uncover their influence on reproduction, development, and disease, such as cancer. Under this theme, we aim to: #1: Characterize how transposons achieve mobilization by hijacking the host cellular machineries. #2: Understand and harness transposon-mediated immunity. #3: Identify transposon-derived neoantigens for cancer immunotherapy.
Circular DNA, also known as extrachromosomal circular DNA (eccDNA/ecDNA), is emerging as a new research topic in our team. This form of DNA is originated from the genome but also can re-integrate into the genome, bringing another layer of genome dynamics. Notably, increasing evidence suggests that oncogenes are frequently amplified in this circular form, propelling tumorigenesis or driving cancer cell drug resistance. As a new frontier, many fundamental questions from circular DNA biology remain unaddressed. Under this theme, we seek to: #1: Investigate how transposon-derived circular DNA is made during development and tumorigenesis. #2: Develop drugs to target the biogenesis of oncogenic circular DNA for cancer therapy.
Driven by our scientific questions, we have established multiple research systems: fruit fly, mouse, cell/tissue culture, human tumor tissues. Our projects are multidisciplinary in nature and involve genetics, genomics, cell biology, cutting-edge imaging and sequencing technologies, and computational biology.