Vilhelm A. Bohr, M.D., Ph.D.
Laboratory of Molecular Gerontology
251 Bayview Boulevard
Baltimore, MD 21224
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.
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.
Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H, Shamanna RA, Kalyanasundaram S, Bollineni RC, Wilson MA, Iser WB, Wollman BN, Morevati M, Li J, Kerr JS, Lu Q, Waltz TB, Tian J, Sinclair DA, Mattson MP, Nilsen H, Bohr VA. NAD<sup>+</sup> Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metab. 2016;24(4):566-581.
Sykora P, Misiak M, Wang Y, Ghosh S, Leandro GS, Liu D, Tian J, Baptiste BA, Cong WN, Brenerman BM, Fang E, Becker KG, Hamilton RJ, Chigurupati S, Zhang Y, Egan JM, Croteau DL, Wilson DM 3rd, Mattson MP, Bohr VA. DNA polymerase β deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes. Nucleic Acids Res. 2015;43(2):943-59.
Akbari M, Sykora P, Bohr VA. Slow mitochondrial repair of 5'-AMP renders mtDNA susceptible to damage in APTX deficient cells. Sci Rep. 2015;5:12876.
Fang EF, Scheibye-Knudsen M, Brace LE, Kassahun H, SenGupta T, Nilsen H, Mitchell JR, Croteau DL, Bohr VA. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 2014;157(4):882-896.
Hou Y, Lautrup S, Cordonnier S, Wang Y, Croteau DL, Zavala E, Zhang Y, Moritoh K, O'Connell JF, Baptiste BA, Stevnsner TV, Mattson MP, Bohr VA. NAD<sup>+</sup> supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc Natl Acad Sci U S A. 2018;115(8):E1876-E1885.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on August 13th, 2018