Trygve O. Tollefsbol

Research Description:

Dr. Tollefsbol's research is primarily involved with cancer and aging epigenetics, the underlying mechanisms of cancer and aging and novel therapeutic approaches to cancer. This work has also involved translational research on leukemia, breast cancer, prostate cancer, ovarian cancer and teratocarcinomas as well as other cancers. The single most important risk factor for developing cancer is age; therefore, both cancer and aging have been a focus of Dr. Tollefsbol's research. The centerpiece of much of the research in aging and cancer genetics involves damage to deoxyribonucleic acid (DNA). Recently telomere shortening has been shown to be associated with DNA damage. Located at the ends of eukaryotic chromosomes and synthesized by the enzyme telomerase, telomeres maintain the length of chromosomes. The majority of human cancer cells express high levels of telomerase and inhibition of telomerase activity kills the cancer cells without effect on most normal somatic cells. The catalytic subunit of telomerase that carries out its enzymatic activity is referred to as human telomerase reverse transcriptase (hTERT). The gene for this protein is inactivated early in embryonic development contributing to cellular aging and it is reactivated in about 90% of cancers, allowing these cells to grow indefinitely.

Studies on the role of telomerase in cancer and aging have made many lists of the most important future research areas in biological sciences. Dr. Tollefsbol's laboratory is interested in the epigenetic regulation of the gene that produces telomerase (hTERT) and in unraveling the mysteries of how this gene relates to cancer and aging. Epigenetic processes are heritable changes that do not involve mutations, but rather, modifications of DNA or its associated proteins and Dr. Tollefsbol's laboratory is interested in these processes as controllers of telomerase gene expression as well as epigenetic mechanisms in cancer and aging in general. Dr. Tollefsbol's laboratory is also interested in discovering novel approaches to inhibiting the telomerase gene in cancers as a future gene therapy strategy and the translational potential of green tea and retinoids in inhibiting telomerase in neoplastic cells. The laboratory is using or has plans to use many cutting-edge technological developments in cancer and aging genetics and translational research such as RNA interference (RNAi), chromatin immunoprecipitation assays and microarray analysis as well as proteomics and metabolomics.

Our laboratory directs a Cell Senescence Culture Facility that provides various types of aging cells to investigators nationwide. This facility is one of only a few of this type in the United States and is designed to not only facilitate studies of aging, but to also participate in new investigations in the mechanisms of cellular aging and age-related diseases such as cancer.

Representative Publications:

Epigenetics Protocols. Tollefsbol, T.O. (ed.) Humana Press, Methods in Molecular Biology, Vol. 287 (ISBN 1-58829-336-X), 2004. Listed by Amazon.com in March of 2005 as the best selling book in the field of epigenetics over the past 10 years. 302 pages.
"Comprehensive and easy to use offers investigators readily reproducible techniques that will further promote progress in this critically important field"-review by Tumori (an international Journal of Experimental and Clinical Oncology).
"Tollefsbol (U. of Alabama) and contributors offer a wide array of leading-edge analytical methods and techniques suitable for studying fundamental biological processes and therapeutic interventions"-review by Powell's Books.

Biological Aging: Methods and Protocols. Tollefsbol, T.O. (ed.) Humana Press, Methods in Molecular Biology, (ISBN 1-58829-658-X), 2007. 414 pages. "Smart researcher, good protocols"-online review by Ruben Agrelo.
"This can be a useful book for biogerontologists. The range and variety of experimental model systems and the cellular and molecular methods employed to address questions in basic and applied aging research require a book like this where one can access practical information and advice. …a welcome source of useful information for researchers intending to find their way into descriptive, analytical and interventive research in biogerontology." Suresh Rattan, Biogerontology DOI 10.1007s10522-007-9120-8, 2008.
"Reminiscent of the excellent books on organic chemistry techniques…this book is written with deep understanding and a sense of sharing. For research gerontologists, this book is a boon." David O. Staats, M.D. (University of Oklahoma Health Sciences Center), Doody Review Services, Barnes & Nobel, 2008.

Telomerase Inhibition: Strategies and Protocols. Andrews, L.G. and Tollefsbol, T.O. (eds.) Humana Press, Methods in Molecular Biology, (ISBN 978-1-58829-683-2), 2007. Focuses on novel translational approaches to cancer therapy. 220 pages.

Cancer Epigenetics. Tollefsbol, T.O. (ed.) CRC Press (Taylor & Francis Group), (ISBN 9781420045796) (In press), 2008. 448 pages (projected).

Epigenetics of Aging. Tollefsbol, T.O. (ed.) Springer Publications (In Progress), 2008.

Research Articles:

Liu, L., van Groen, T., Kadisha, I. and Tollefsbol, T.O. DNA methylation impacts on learning and memory in aging. Neurobiology of Aging [epub ahead of print] PMID: 17850924, 2008. Listed among the top 8 "hottest articles" published in this journal by ScienceDirect's Top25 Hottest Articles, 2008.

Berletch, J., Liu, C., Love, W.K., Andrews, L.G., Katiyar, S. and Tollefsbol, T.O. Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG. Journal of Cellular Biochemistry, 103, 509-519, 2008.

Lai, S.R., Cunningham, A.P., Huynh, V.Q., Andrews, L.G., and Tollefsbol, T.O. Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop. Experimental Cell Research 313, 322-330, 2007.

Liu, L., Andrews, L.G., and Tollefsbol, T.O. Loss of the polycomb protein BMI-1 promotes cancer-specific cell death. Oncogene 25, 4370-4375, 2006.

Cunningham, A.P., Love, W.K., Zhang, R.W., Andrews, L.G., and Tollefsbol, T.O. Telomerase inhibition in cancer therapeutics: Molecular-based approaches. Current Medicinal Chemistry 13, 2875-2888, 2006.

Ulrey, C.L., Liu, L., Andrews, L.G., and Tollefsbol, T.O. The impact of metabolism on DNA methylation. Human Molecular Genetics 14, R139-R147, 2005.

Liu, L., Lai, S., Andrews, L.G., and Tollefsbol, T.O. Genetic and epigenetic modulation of telomerase activity in development and disease. Gene 340, 1-10, 2004. Listed among the top 4 "hottest articles" published in Gene by ScienceDirect's Top25 Hottest Articles.

Liu, L., Saldanha, S.N., Pate, M.S., Andrews, L.G., and Tollefsbol, T.O. Epigenetic regulation of human telomerase reverse transcriptase promoter activity during cellular differentiation. Genes, Chromosomes, and Cancer 41, 26-37, 2004.

Casillas, M., Brotherton, S.L., Andrews, L.G., Ruppert, J.M., and Tollefsbol, T.O. Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements. Gene 316, 57-65, 2003. Listed in J. Anti-aging Medicine (vol. 6, p. 341, 2003) among the most "important or provocative articles by noted experts" in the field of cellular senescence.

Casillas, M.A, Lopatina, N., Andrews, L.G., and Tollefsbol, T.O. Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically-transformed human fibroblasts. Molecular and Cellular Biochemistry 252, 33-43, 2003. Listed in the J. Anti-aging Medicine ( vol. 6, p. 344, 2003) among the most "important or provocative articles by noted experts" in the field of gene expression and gene therapy.

Saldanha, S., Andrews, L.G., and Tollefsbol, T.O. Analysis of telomerase activity and detection of its catalytic subunit, hTERT. Analytical Biochemistry 315, 1-21, 2003. Listed among the most downloaded papers of 2003 in Analytical Biochemistry.

Saldanha, S., Andrews, L.G., and Tollefsbol, T.O. Assessment of telomere length and factors that contribute to its stability. European Journal of Biochemistry 270, 389-403, 2003. Listed as the fourth most accessed EJB paper of 2003.

Liu, L., Wylie, R., Andrews, L., and Tollefsbol, T.O. Aging, cancer and nutrition: the DNA methylation connection. Mechanisms of Ageing and Development 124, 989-998, 2003. This publication was the subject of news stories in Genetics & Environmental Health Week (March 3, 2004, p. 60-61) and Managed Care Business Week (March 2, 2004, p. 73-74). Title of news story: "Nutrition contributes to aging and cancer development." It was also listed among the top 8 in ScienceDirect's Top25 Hottest Articles.

Lopatina, N., Haskell, J.F., Andrews, L.G., Poole, J.C., Saldanha, S., and Tollefsbol, T.O. Differential maintenance and de novo methylating activity by three DNA methyltransferases in aging and immortalized fibroblasts. J. Cellular Biochemistry 84, 324-334 2002. Listed among the most important articles of 2002 in biological sciences by the Faculty of 1000.

Poole, J.C., Andrews, L.G., and Tollefsbol, T.O. Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene 269, 1-12, 2001. Cited as one of the top down-loaded articles from ScienceDirect according to the Editors of Gene.

Ahmed, A. and Tollefsbol T.O. Telomeres and telomerase: Basic science implications for aging. J. American Geriatrics Society 49, 1105-1109, 2001. Selected among the Best Papers of 2001 in Geriatric Pathology.

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