Our research is to understand the evolution and adaption of human regulatory networks, with a focus on the impact of these processes on human health and disease. In particular, we investigate the evolutionary model of mobile elements (or transposable elements) and their roles in basic biology and cancer, including their genetic and epigenetic regulation.
We use integrative and systems methods. We develop statistical and computational algorithms to explore the human genome, to integrate cross-species comparative and high-throughput genomics data. We test our hypothesis and validate our predictions in the wet lab.
Our interests span areas of genomics, epigenomics, evolution, computation, systems biology and many more. We also have a general interest in large data integration and visualization, including developing genome and genomics browsers, and developing tools for analyzing high-throughput genomics data, including next-gen sequencing data.
Understanding of the mobile elements in our genome remains poor, but mobile elements play a very significant role in genome evolution and human biology as well as disease. Our research will focus on the effect of mobile elements on genome evolution and their roles in basic biology and cancer. How extensive are the interactions between different repetitive elements and transcription factors? How are they regulated genetically, epigenetically, temporally and spatially? How is repression of regulatory elements derived from repetitive DNA established and maintained? How do functional enhancers that are exaptations from ancient transposons escape this inactivation, and how large a role do they play in gene regulation? How does a breakdown of regulation of and by repetitive elements contribute to human cancers? Our mission is to address these questions using integrative systems methods, with both computational and experimental approaches.
Our working hypotheses are:
It is important to establish an evolutionary model in which we can examine roles played by transposable elements in shaping regulatory networks. We are constructing a computational framework to detect and assess the potential impact of transposable elements on the human transcription regulatory networks.
An exciting hypothesis stemming from our evolutionary theory is that transposable element sequences in the human genome are functionally potent and are tightly regulated, and that mis-regulation of these sequences may lead to human diseases. We are investigating the biological functions of mobile elements in the human genome and how they are regulated. We will also test a hypothesis that mis-regulated transposon sequences may contribute to human cancer.
We are part of the Epigenome Roadmap Project. Our lab is a member of one of four NIH funded Reference Epigenome Mapping Centers (REMCs). We are working cooperatively with other Mapping Centers and the Data Coordination Center (EDACC) funded by this Roadmap mechanism to comprehensively map epigenomes of select human cells with significant relevance to complex human disease. Our center, consisting of scientists at UCSF, UC Davis, UCSC and the British Columbia Genome Sciences Centre has the broad expertise that this project requires. We are focusing on cells relevant to human health and complex disease including cells from the blood, brain, breast and human embryonic stem cells. We will incorporate high quality, homogeneous cells from males and females, and two predominant racial groups, and biological replicates of each cell type.
Production of comprehensive maps will include 6 histone modifications selected for their opposing roles in regulating active and inactive chromatin, DNA methylation and miRNA and gene expression. This epigenetic data, along with genetic and expression data will be integrated using advanced informatics to address fundamental roles of epigenetics in differentiation, maintenance of cell-type identity and gene expression.
Our reference epigenomes will enable new disciplines including human population epigenetics, comparative epigenomics, neuroepigenetics, and therapeutic epigenetics for tissue regeneration and reversal of disease.
Two specific roles our lab plays in our REMC:
We are committed to transforming theories and algorithms into software applications that not only facilitate our own research, but also benefit researchers in a broader scientific community. Specifically, we are interested in developing and implementing algorithms in the following areas: