Affiliation: UCSD SOM
Assistant Professor of Cellular and Molecular Medicine
Dr. Ren received his B.S. degree from the University of Science and Technology of China,
Hefei, in 1991, a masters in computer sciences from Harvard, and a Ph.D. in Biochemistry
from Harvard in 1998. He did post-doctoral work at the Whitehead Institute for Biomedical
Research at MIT and became head of the Laboratory of Gene Regulation at the Ludwig
Institute for Cancer Research in 2001.
Of the roughly 3 billion nucleotides in the human genome, it is estimated that 2-3% may
correspond to the transcriptional regulatory elements that define a highly specific gene
expression program in human cells (Lander et al., 2001; Waterston et al., 2002). These DNA
sequences allow each gene to be transcribed at the appropriate time and place during
development, and allow each cell in the body to respond appropriately to environmental
cues. These sequences also allow the human being to evolve from its ancestors.
Delineating the identity and function of the transcriptional regulatory elements is therefore
the key to understanding human biology and the molecular basis of diseases.
One research project in the lab is to discover the transcriptional regulatory elements in
human genome using a novel high throughput approach that we developed, known as
genome-wide location analysis (GWLA) or ChIP-on-chip. This method involves
immunoprecipitation of the DNA associated with a particular protein from crosslinked cells,
followed by quantitative amplification and simultaneous detection of the enriched
sequences with DNA microarray technologies (Figure 1).
We are currently applying GWLA to a panel of well-characterized regulatory proteins and
histones with specific modifications that are known to generally associate with
transcriptional regulatory elements in vivo, with a goal to determine the sequence features
in the human genome that carry out transcriptional regulatory function.
Another area of research in the lab is to understand genetic programs of tumorigenesis.
Cancer is a disease characterized by aberrant gene expression that result from genetic
alterations in cell1s transcriptional regulatory networks. Many transcriptional regulators
have been linked to the causes of cancer, and identification of their genomic binding sites in
cells offers a great opportunity to delineate the molecular pathways of malignant
transformation and develop better treatment. To this end, we have formed an integrated
approach to investigate the genome-wide location and function of c-Myc, a transcription
factor responsible for many human cancers. Our initial experiments have resulted in the
identification of a complex transcriptional regulatory program controlled by c-Myc that
involves more than 700 c-Myc targets. These genes participate in a wide spectrum of
cellular processes, including protein biosynthesis, DNA replication, cell cycle check-point
control, DNA damage repair, and apoptic signaling pathways. We are currently examining
the role that each gene play in the c-Myc transformation process.
References From PubMed (NCBI)