Vivian G. Cheung
Associate Professor, Dept of Pediatrics and Genetics

Genetics and Gene Regulation Program

Address

office
516G, Abramson Research Center
The Children’s Hospital of Philadelphia
3615 Civic Center Blvd.
Philadelphia, PA 19104-4318

lab
509 Abramson Research Center
The Children’s Hospital of Philadelphia
3615 Civic Center Blvd.
Philadelphia, PA 19104-4318

Office tel.: 215 590-4950
Lab tel.: 215 590-2664
E-mail: vcheung@mail.med.upenn.edu

Link(s)

Dr Cheung at the Genomics Group

Education

UCLA, BS (Microbiology), 1989

Tufts University, MD, 1993

Research Interests

• Human Genetics, Genomics

Key words: Human Genetics, Genomics.

Search PubMed for articles

Description of Research

Our research interest is in human genome variation. We are using genome-wide approaches to study the genetic basis of human phenotypes and traits.

Genetics of Gene Expression in Humans
Traditionally, we think of phenotypes as characteristics such as height, eye-color and serum cholesterol level. Today, with tools such as gene expression microarrays, we can expand these quantitative phenotypes to include expression levels of genes.
We are assessing the degree of variation in the expression level of genes among normal individuals. The human genome project has provided a detailed description of the variation in DNA sequence, but little is known about natural variation in gene expression. We begin by using microarrays to profile the expression levels of 10,000 genes in several hundred individuals that are members of large 3-generational families. Our goal is to identify the genes whose mRNA transcript levels vary the most among individuals. These variable genes are most amenable to genetic dissection. Then, we are using genetic analysis and computational approaches to map and identify the cis- and trans-acting elements that regulate expression levels of the “variable” genes.

Genetics of Radiosensitivity in Humans
Although it is known that individuals have different responses to ionizing radiation, little is known about the genetic basis of this variation. Humans are exposed to radiation through the environment and in medical procedures. By understanding the genetic basis of radiosensitivity, we hope to identify radiosensitive individuals and to better understand cellular response to radiation exposure.
In part of this project, we are examining the expression profiles of heterozygous carriers of ataxia telangiectasia (AT). AT is a rare disease but its carriers are relatively common, about 1 per 100 individuals in the US. Studies have shown that AT patients and AT carriers are radiosensitive. AT is a typical autosomal recessive disease where carriers cannot be identified by physical exams or biochemical tests. Yet, by expression analysis, we found a set of genes whose expression levels are significantly different between AT carriers and non-carriers. Our result shows that AT carriers have a distinctive expression phenotype. It provides an opportunity for carrier testing and a basis for a better understanding of the long debated risk of cancer among AT carriers. We are extending this study of AT carriers to carriers of other diseases such as Bloom Syndrome, Nijmegen Breakage Syndrome and Fanconi Anemia whose carriers may also be radiosensitive.
In another part of this project, we are studying transcriptional response of human cells to radiation and assessing the extent of variation in this response. We are using genomic approaches to identify the genes and pathways that are involved in radiation response.

Recent Publications

Morley M., Molony CM., Weber T., Devlin JL., Ewens KG., Spielman RS., Cheung VG.: Genetic analysis of genome-wide variation in human gene expression. Nature, 430: 743-747, 2004.

Correa CR., Cheung VG.: Genetic variation in radiation induced expression phenotypes. Amer. J. Hum. Genet., 75(5):885-90, 2004

Jen KJ., Cheung VG.: Identification of novel P53 target genes involved in ionizing radiation stress response. Cancer Research, 65:7666-7673, 2005

Cheung VG., Spielman RS., Ewens KG., Weber TM., Morley M & Burdick JT.: Mapping determinants of human gene expression by regional and whole genome association. Nature, 437: 1365-1369, 2005

Burdick JT., Chen W., Abecasis GR. & Cheung VG.: Determining genotypes in pedigrees by inference. Nature Genetics 38: 1002-1004, 2006

Lab

Rotation Projects

1. Genetics of Gene Expression: To assess variation in human gene expression and to identify the determinants of this variation by using a combination of techniques, including microarrays, reporter assays and chromatin IP.
2. Variation in Meiotic Recombination: To identify hotspots of recombination by localizing sites for meiotic recombination in the human genome and to validate them experimentally using haploid cells.
3. Cellular Response to Radiation Exposure: To identify genes that are involved in radiation response in normal individuals and in patients with defects in DNA repair.

Lab personnel:

Alan Bruzel, PhD, Lab Manager
Reshmi Chowdhury, Graduate Student, Master of Biotechnology Program
Josh Burdick, Programmer
Colleen McGarry, Research Coordinator
Michael Morley, Bioinformatics Specialist
Renuka Nayak, Graduate Student
Vishal Nayak, Senior Data Analyst
Eunice Shin, Undergraduate Student
Denis Smirnov, PhD, Senior Scientist
Chris Weber, Graduate Student
Teresa Weber, Research Specialist