HomeResearchIntramural ResearchResearch Branches at NHGRIGenome Technology Branch Wolfsberg Lab

Tyra Wolfsberg, Ph.D. Associate Investigator Genome Technology Branch Associate Director Bioinformatics and Scientific Programming Core A.B. Princeton University, 1988 Ph.D. University of California, San Francisco, 1995 (301) 435-5990 (301) 480-9899 tyra@nhgri.nih.gov Building 50, Room 5228B 50 South Dr, MSC 8004 Bethesda, MD 20892-8004 Selected Publications Current Topics in Genome Analysis 2008 Online Research Resources Developed at NHGRI

Dr. Wolfsberg applies bioinformatics techniques to a variety of genomic research questions, such as identifying gene-regulatory sequences on a genome-wide basis and understanding the behavior of retroviruses used as vectors in gene-therapy experiments. As Associate Director of National Human Genome Research Institute¿s (NHGRI) Bioinformatics and Scientific Programming Core, she also devotes part of her time to overseeing the day-to-day operation of this state-of-the-art computing facility.

Dr. Wolfsberg's research primarily involves collaborations with other NHGRI and outside scientists. For example, she is collaborating with Dr. Francis Collins' group to develop a genome-wide library of gene-regulatory sequences. This effort aims to scale up a proven but labor-intensive method of finding gene-regulatory elements-locating transcriptionally active regions of DNA by finding sites that are sensitive to deoxyribonuclease (DNase).

Dr. Wolfsberg has devised an approach for analyzing putative DNase-sensitive regions and establishing whether they represent transcriptionally active regions. Her analyses have shown that such hypersensitive sites do indeed reside more frequently in regions known to contain regulatory elements, such as segments upstream of genes, sequences within CpG islands (unmethylated regions of the genome that are associated with the 5¿ ends of most housekeeping genes and many tissue-specific genes), and regions where the human and mouse genomes are similar. Dr. Wolfsberg and her colleagues are now scaling up this process to deal with up to 100,000 such sites in the human genome. This scale-up involves the development of new computer protocols for handling the sheer volume of raw data in a way that is computationally efficient and tractable.

In another line of research, Dr. Wolfsberg is working with other NIH laboratories to determine whether the retrovirus vectors currently used in ex vivo gene-therapy experiments integrate preferentially into the DNA of their target cells or at random. The answer to this question could have a major bearing on the prospects for gene therapy using these vectors. Originally, it was believed that the retroviruses used to carry therapeutic genes in ex vivo gene therapy would integrate themselves in a random manner and that the chances of their disrupting a gene or interfering with gene expression were remote.

However, in 2002, it was revealed that three out of ten children who had been treated for X-linked severe combined immunodeficiency type 1 in a French gene-therapy experiment had developed uncontrolled proliferation of mature T cells-a leukemia-like disorder. In both cases, some of the recombinant retroviruses had inserted themselves near the promoter of the LMO2 oncogene, which encodes a transcription factor involved in hematopoiesis. In late 2003, the French team carrying out the trial concluded that integration of the virus at that site led to uncontrolled overexpression of the gene. Since then, research into whether particular retrovirus vectors favor certain sites in the genome over others has produced mixed results (see Genetics and Molecular Biology Branch). Dr. Wolfsberg is helping her collaborators at NHGRI and at the National Heart, Lung and Blood Institute to determine whether these viral vectors integrate randomly or preferentially.

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Last Updated: August 1, 2008