| Laboratory of Molecular Gerontology |
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| Vilhelm A. Bohr, M.D., Ph.D., Senior Investigator Chief, Laboratory of Molecular Gerontology |
 Dr. Bohr received his M.D. in 1978, Ph.D. in 1987, and D.Sc. in 1987 from the University of Copenhagen, Denmark. After training in neurology and infectious diseases at the University Hospital in Copenhagen, Dr. Bohr did a postdoctoral fellowship with Dr. Hans Klenow at the University of Copenhagen, Denmark. He then worked with Dr. Philip Hanawalt at Stanford University as a research scholar from 1982-1986. In 1986 he was appointed to the National Cancer Institute (NCI) as an investigator, becoming a tenured Senior Investigator in 1988. Dr. Bohr developed a research section in DNA repair at the NCI. In 1992 he moved to the NIA to become Chief of the Laboratory of Molecular Genetics. His main contributions have been in the area of DNA repair. He has worked on many aspects of DNA damage and its processing in mammalian cells. He developed a widely used method for the analysis of DNA repair in individual genes and found that active genes are preferentially repaired. This observation was a major advance in the clarification of the tight interaction between DNA repair and transcription, a process termed transcription-coupled repair. In recent years numerous papers from his laboratory have focused on mechanisms of DNA damage processing, particularly on nucleotide excision repair and transcription coupling. A main interest now is to elucidate how these processes change in relation to aging.Research Interests: The Laboratory of Molecular Gerontology (LMG) investigates DNA related mechanisms such as genomic instability, DNA repair, DNA replication, and transcription. We consider the increased DNA damage accumulation in senescence as the major molecular change with aging, and this DNA damage may eventually inactivate individual genes and lead to a deterioration of the organism, which is characteristic of the senescent phenotype. DNA damage maybe a major cause of age-associated diseases, notably cancer. The goal of LMG is thus to understand the underlying mechanisms involved in DNA damage formation and its processing as well as the changes that take place with aging and that make aging cells susceptible to cancer. DNA repair is likely to play a critical role, and we have a special interest in the fine structure of DNA repair, which includes the study of the DNA repair process in individual genes. We are investigating the molecular mechanisms involved in DNA repair and in genomic instability in normal, senescent and cancer cells. We are investigating nucleotide excision repair and base excision repair in vitro, in fractionated cell extracts, and in intact cells. We are also interested in the molecular processes that interact with DNA repair. They include transcription, replication, somatic mutation and mitochondrial alterations. |
| The area of oxidative DNA damage and its processing is of particular interest to us. Repair of oxidative DNA base lesions is investigated in whole cells, in mitochondria and also in cancer cells.The accumulation of DNA damage with age could be a result of a gradual decline in DNA repair capacity. Work from this and other laboratories suggests that this decline is not readily detectable in the overall genome, but may rather be a decline in the gene specific or transcription-coupled component of the DNA repair process. We are studying the molecular deficiencies in human premature aging disorders using cell biological approaches and biochemistry. |
| In the Laboratory we are generally interested in a better understanding of the processes that lead to genomic instability. Aside from the DNA repair process, which clearly is of importance in maintaining genomic stability, we are interested in the processes of mutation and the role of DNA polymerases in this process. Recently, a number of new DNA polymerases have been discovered and some of these have low fidelity which can lead to mutation. |
| Somatic hypermutation is a distinct process, which is central to the normal immune response. We are interested in this process and how it relates to DNA repair and other processes and whether it changes with age. |
| The Laboratory is studying DNA helicases and exonucleases such as that of the Werner syndrome protein. These enzymes are also essential in maintaining genomic instability and we are investigating their function at a biochemical level and their interactions with other proteins. |
| An interesting DNA structure that may arise in certain parts of the genome is the triple helix. These can lead to genomic instability and are of significant biological relevance. In addition, these structures can be used to mediate gene targeted DNA damage, and this approach is established in the laboratory. |
| We are involved with a number of studies using material from the Baltimore Longitudinal Study of Aging (BLSA). In DNA samples from individuals in this study, we are examining various aspects of genomic instability and how it changes with aging and premature aging diseases. |
| Contact Information: Laboratory of Molecular Gerontology Biomedical Research Center, room 06B133A 251 Bayview Boulevard, Suite 100 Baltimore, MD 21224-6825 Phone 410-558-8162 Fax 410-558-8157 E mail vbohr@nih.gov For more information about the Laboratory: http://www.grc.nia.nih.gov/branches/lmg/lmg.htm |
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