Research Overview

The Zhang lab at the UCSD Bioengineering department is interested in developing novel genome technologies towards the applications in personalized genome medicine and stem cell research.

Technology: We are developing various methods for synthesis, manipulation and sequencing of DNA molecules. Examples include

• large-scale DNA synthesis on programmable DNA chips;
• isolation, amplification and sequencing of single chromosomal molecules;
• digital profiling of gene expression and allele-specific gene expression;
• targeted genome capture and sequencing.

Informatics: Almost every single aspect of our genome-scale studies depends on bioinformatics. We do large-scale "manipulation" of DNA molecules in computer before and after processing them in test tubes. Here are some examples:

• designing DNA probes for capturing & sequencing SNPs/Exons, which also includes various simulation;
• mapping and analysis of next-generation DNA sequencing data;
• de novo assembling of single-cell genome sequencing data;
• haplotype assembling and analysis of single molecule sequencing data.

Biology: Our research interest lies in the genetics of individuality. We ask what are the phenotypic differences among human individuals or cell lines derived from these individuals, and what are the genetic factors that can explain such differences (formally termed as phenotypic variations). We seek to identify functional genetic variations in the human genome, which often contribute to the susceptibility of human complex diseases. We use a system biology approach by combining large-scale genotyping, phenotyping, functional assays, and analysis of gene regulation networks or pathways.

We perform these studies under two different contexts:

• Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPS):
  • We are performing large-scale phenotyping and functional genomic analyses on a panel of hESC lines established at the Harvard Stem Cell Institute (HUES lines).
  • We are also performing genomic analyses of iPS cells to understand the de-differentiation and re-differentiation processes.
• Personal Genome Project: we have received UCSD's IRB approval to perform functional analyses on the samples collected under the Personal Genome Project. Another web site about PGP, which has a link to a video clip of Esther Dyson on the Charlie Rose Show talking about PGP.

Potential graduate student rotation projects:

• Design and fabrication of microfluidic devices for single chromosome analysis.
• Development of remapping strategies for next-generation DNA sequencing data.