Beverly H. Koller, PhD

Research Interests

Key words: mouse models for human diseases, genes that modify disease progression

Our lab is using the recently developed technique known as gene targeting to create animal mouse models for human diseases and to identify genes that modify the progress of these diseases. The technique of gene targeting, which allows us to introduce specific changes into the genomes of experimental animals, relies on recent advances in the fields of homologous recombination and embryonic stem (ES) cell technology. The first step in this procedure, once the gene to be modified has been chosen, is to obtain corresponding genomic DNA sequences using stardard cloning techniques. After introducing desired mutations into the cloned DNA using conventinal molecular biology techniques, the genomic sequences are incorporated into a plasmid known as a targeting vector. When this plasmid is introduced into mouse ES cells, the altered genomic sequences are able to undergo homologous recombination with the corresponding endogenous sequences, thereby inroducing the desired modifications into the moust genome. ES cells are unique in that they can be grown in tissue culture while maintaining their totipotency. Thus, one ES cells carrying the desired mutation are identified, they can be returned to an embryo, resulting in the formation of a chimeric animal. If the embryonic stem cells participate in the formation of the germ line of the chimeric animal. the mutation will be transmitted to the chimera’s offspring, and a mouse line carrying the desired mutation will be created. The effect of this alteration can then be studied in vivo. This technology has opened an exciting new avenue for addressing numerous biological and medical problems.

We have used gene targeting to generate an animal model for the most common genetic disease n the Caucasian population, cystic fibrosis. We are continuing to characterize this animal and to modify it to produce a disease that more closely resembles human cystic fibrosis. A second area in which our lab is interested involves the study of the inflammatory processes involved in allergic responses, asthma, and arthritis. Our current efforts are aimed at generating animals deficient in various factors that are believed to be important in these diseases. By providing us with a better understanding of the immunological processes that underlie allergic responses, asthma and arthritis, these animals should help us to identify more effective treatments for these diseases.

Publications

PubMed Link

Lab Members

• Martina Kovarova, Research Assistant Professor, Email
• Jay Snouwaert, Research Associate, Email
• Rachel Lail, Graduate Student, Email
• Anne Latour, Technician. Email
• Mytrang Nguyen, Technician, Email
• Zhidan Xiang, Postdoctoral fellow, Email
• Michael Backlund, Postdoctoral fellow, Email
• Steven Lommatzch, MD, Pulmonary fellow, Email
• Sarah Keilson, Undergraduate student, Email

Beverly Koller in UNC Genetics News