Trygve O. Tollefsbol

 

Professor, Epigenetics and Gene Regulation in Cancer and Aging

Contact


(205) 934-4573
(205) 975-6097

Ph.D. (Molecular Biology), 1982, University of North Texas Health Sciences Center

 

Research Description : http://www.uab.edu/uabmagazine/2011/september/epigenetics

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.

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 gene expression in cancer and aging in general.  We are interested in discovering novel approaches of modifying epigenetic gene expression in cancers and aging and the translational potential of epigenetic-modulating nutritional compounds in inhibiting cancer and impacting aging. 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.

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 also 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.  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.  

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:

Books:

Epigenetics Protocols. Tollefsbol, T.O. (ed.) Humana Press (ISBN 1-58829-336-7), 2004. 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 (ISBN 1-58829-658-X), 2007. 414 pages.
"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.

"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 9, 137, 2008.

Telomerase Inhibition: Strategies and Protocols. Andrews, L.G. and Tollefsbol, T.O. (eds.) Humana Press (ISBN 978-1-58829-683-2), 2007. 220 pages.
"In this text, 30 international academics and researchers contribute 14 chapters providing researchers with a diverse and comprehensive set of tools with which to study telomerase inhibition." SciTech Book News, June, 2008.

"Given the thousands of articles published each year with the keyword “telomerase”, this summary of the methods related to the analysis of telomerase is welcome. Overall this book will be a useful resource for researchers performing telomerase-related experiments. This book features a compendium of methods and provides the researcher with a set of practical tools, as all protocols are described in a very clear and accurate fashion.” Current Medicinal Chemistry, 3, 1135-1140, 2008.

Cancer Epigenetics. Tollefsbol, T.O. (ed.) CRC Press (Taylor & Francis Group), (ISBN 9781420045796), 2008. 446 pages.
"Tollefsbol (U. of Alabama at Birmingham) and 50 contributors—many of them pioneering researchers—provide a variety of topics ranging from the role of epigenetics in the basic mechanisms of tumorigenesis to the most current epigenetic drugs being produced for cancer therapy. The volume…would serve as a reference for researchers and practitioners interested in tumor biology and cancer therapy and as a textbook for advanced courses in disciplines such as genetic diseases, molecular biology and cancer.” SciTech Book News, March, 2009.

"Edited and partly written by Dr. Tollefsbol, this book aims to provide a comprehensive and up-to-date coverage of all aspects of cancer epigenetics... Overall this book represents an aggressive aim, with endeavor to summarize the vast amount of information from a very rapidly developing field. …a valuable tool for those who wish to conduct research on epigenetics and hope to grasp the key concepts instantly. This is an excellent book on cancer epigenetics that will be of value to clinical scientists, postgraduate students, postdoctoral fellows, and basic scientists who wish to conduct basic or translational cancer research… The exhaustive source of references in this book will allow researchers to rapidly locate key references and grasp key concepts essential to the rapidly evolving field.” Suet Yi Leung, Gastroenterology 137, 2177-2178, 2009.

Epigenetics of Aging. Tollefsbol, T.O. (ed.) Springer (ISBN 978-1-4419-0638-0; e-ISBN 978-4419-0639-7), 2010. 469 pages.
Nature 464, 1130-1131, April 22, 2010. “Why twins age differently” “Epigenetics of Aging”, a collection of articles assembled by molecular biologist Trygve Tollefsbol, gives us a contemporary view of the epigenetic processes involved in ageing. “Epigenetics of Aging” reminds us that mysterious and fascinating processes govern the last phase of life in all organisms.”

Handbook of Epigenetics: The New Molecular and Medical Genetics. Tollefsbol, T.O. (ed.) Academic Press (ISBN: 978-0-12-375709-8), 2011. 624 pages.
"The Handbook of Epigenetics contains an impressive collection of 37 articles, mainly dealing with the biology of epigenetics. Covered topics range from molecular marks and mechanism, other model systems, epidemiology, aging and the brain to diseases…. In summary, the Handbook of Epigenetics provides a unique and useful combination of information and it is a valuable addition to the bookshelf of scientists with experience in the field."--CHEMBIOCHEM

Epigenetics Protocols, Second Edition. Tollefsbol, T.O. (ed.) Humana Press (ISBN: 978-1-61779-315-8), 2011. 332 pages.

Epigenetics in Human Disease. Tollefsbol, T.O. (ed.) Academic Press (ISBN 9780123884152), 2012. 592 pages.
"This volume constitutes a comprehensive survey of the emerging field of epigenetics in the etiology, progression, diagnosis, prognosis and treatment of human diseases… With its translational focus, this book will serve as valuable reference for both basic scientists and clinicians alike."--Anticancer Research, Volume 33, Issue no. 5, May 2013

"This book covers a huge range of topics, from early life effects on adult disease to epigenetic changes occurring with aging and senescence. Especially pertinent are the several chapters on epigenetic treatments for disease including drugs, miRNA/siRNA, natural substances and foods. With up to date coverage of an ever expanding field, Epigenetics in Human Disease will be a great resource for clinicians, researchers and students."--Craig Cooney, Investigator, Research Service, Veteran's Affairs Medical Center, Little Rock, AR & Affiliate Scientist, Nanotechnology Center, University of Arkansas, Little Rock, AR

Biological Aging - Methods and Protocols, Second Edition. Tollefsbol, T.O. (ed.) Humana Press (ISBN 978-1-62703-555-2), 2013. 354 pages.

Translational Epigenetics. Tollefsbol, T.O. (ed.) Academic Press (under contract and in progress), 2014.

Personalized Epigenetics. Tollefsbol, T.O. (ed.) Academic Press (under contract and in progress), 2015.


Representative Research Articles:

Mitchell, N.E., Wilson, M.L., Bray, M.S., Crossman, D.K. and Tollefsbol, T.O. Real-time methylomic aberrations during initiation and progression of induced human mammary epithelial cell tumorigenesis. Epigenomics 5, 155-165, 2013.

Chen, H., Landen, C.N., Li, Y., Alvarez, R.D., and Tollefsbol, T.O. Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and BCL-2 down-regulation. Experimental Cell Research 319, 697-706, 2013.

Meeran, S.M., Patel, S.N., Li, Y., and Tollefsbol, T.O. Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications. PLoS One 2012;7(5):e37748, 2012.

Li, Y., Daniel, M., and Tollefsbol, T.O.  Epigenetic regulation of caloric restriction in aging.  BMC Medicine 9, 98, 2011. 

Featured article in BMC Medicine.  This paper also received “highly accessed” status.  This paper was also the subject of a news article in The Australian, a national newspaper in Australia and was  the subject of a news article in Australian Doctor, the “best-read medical publication in Australia”.

Hardy, T. M. and Tollefsbol, T.O.  The epigenetic diet:  Impact on the epigenome and cancer.  Epigenomics 3, 503-518, 2011.

Li, Y. and Tollefsbol, T.O.  p16INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.  PLoS One 6(2): e17421, 2011.

Meeran, S.M., Patel, S.N, Chan, T.H., and Tollefsbol, T.O.  A novel prodrug of epigallocatechin-3-gallate:  Differential epigenetic hTERT repression in human breast cancer cells.  Cancer Prevention Research 4, 1243-1254, 2011.

Li, Y., Liu, L., and Tollefsbol, T.O. Glucose restriction can extend normal cell lifespan and impair cancer cell growth through epigenetic control of hTERT and p16 expression. FASEB Journal 24, 1442-1453, 2010.

Selected by the editors of FASEB Journal for press release. Received several hundred news stories online and also appeared on the UAB main page and the front page of Birmingham News, 2009. Also topic of television interviews of Dr. Tollefsbol (Fox 6 News), 2010. Also discussed in Science News online: Scientists take important step toward the proverbial fountain of youth

Meeran, S.M., Ahmed, A. and Tollefsbol, T.O.  Epigenetic targets of bioactive dietary components for cancer prevention and therapy.  Clinical Epigenetics 1, 101-116, 2010. 

Subject of hundreds of online news articles and featured on UAB Main Web Page, 2011.

Li, Y., Yuan, Y.Y., Meeran, S.M., and Tollefsbol, T.O.  Synergistic epigenetic reactivation of estrogen receptor-a by combined green tea polyphenols and histone deacetylase inhibitor in ERa-negative breast cancer cells.  Molecular Cancer 9:274-285, 2010. 

Listed as a “Highly Accessed” articleAlso, subject of news story in MDLinx Editorial Team, 2010.

Meeran, S.M., Patel, S.N., and Tollefsbol, T.O. Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cells. PLoS One, Jul 6;5(7):e11457, 2010.  

Subject of news article in Birmingham Science News Examiner, July 9, 2010.  Also subject of news article in ScienceNow, 34, 4, 2010 “Finding the Cruciferous Cancer-Prevention Link”.