Elizabeth H. Blackburn is a leader in the area of telomere and telomerase research. She discovered the molecular nature of telomeres - the ends of eukaryotic chromosomes that serve as protective caps essential for preserving the genetic information - and co-discovered the ribonucleoprotein enzyme telomerase. Born in Australia, she earned her BSc (1970) and MSc (1972) degrees from the University of Melbourne, received her PhD (1975) from the university of Cambridge, and did postdoctoral work in molecular and cellular biology at Yale University (1975-1977). She was a faculty member at the University of California, Berkeley from 1978 until 1990, when she joined the Faculty at the University of California, San Francisco, where she is currently Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics. She is also a Non-Resident Fellow of the Salk Institute. She has won many prestigious awards throughout her career. She was elected Fellow of the American Academy of Arts and Sciences (1991) and the Royal Society of London (1992). She was elected Foreign Associate of the National Academy of Sciences (1993) and Member of the Institute of Medicine (2000). She served on the President's Council on Bioethics (2002-2004) and has been awarded honora- ry degrees by 11 universities. She received the Albert Lasker Basic Medical Research Award in 2006, and in 2007 was named one of Time magazine's 100 most influential people. In 2008 she was the North American laureate for the L'Oréal-UNESCO For Women in Science awards. In 2009, Professor Blackburn was awarded the Nobel Prize in Physiology or Medicine.
Perspectives on Telomeres and Telomerase in Human Aging and Cancers
Telomeres protect eukaryotic chromosome ends, and their compromise can lead to maladaptive cellular changes and block tissue replenishment. As humans age, average telomere length declines. Independently of age and other known mortality risk factors, observed telomere shortness predicts all-cause human mortality rates. Non-genetic factors associated with telomere shortness include social, environmental and lifestyle factors, such as smoking or exercise.
The cellular ribonucleoprotein enzyme telomerase, by adding telomeric DNA repeat sequences to the ends of chromosomes, can compensate for their attrition. Stem cells and a majority of malignant human cancer cells have high telomerase activity that prolongs cell division capacity. Insufficient telomerase leads to progressive telomere shortening during cell divisions and eventual cellular senescence. How telomere maintenance perturbations – upward or downward – interact with cancer etiology and progression varies among different cancer types. Genetic deficiencies in telomerase (caused by monogenetic mutations) hasten telomere shortening and cause a spectrum of diseases, including certain cancers: hematological (leukemias and myelodysplastic syndrome), squamous-cell skin and gastrointestinal cancers. These inherited telomere syndromes also include loss of immune function through loss of bone marrow stem cell reserves. This potentially impacts on the immune surveillance mechanisms that can control cancers. However, for certain subsets of cancers, subtly over-active telomere maintenance is cancer-promoting. For instance, common germline allelic variants in known telomere maintenance genes, associated with longer leukocyte telomere length, raise risks of melanomas, non-smokers’ lung cancer and many gliomas. This mode of increased telomere maintenance may prolong the survival of cancer-prone or pre-cancerous cells, increasing the probability that the multiple steps toward tumorigenesis can occur.
Telomere length maintenance is highly interactive and telomere shortness shows much greater predictive power when combined with other factors than when considered alone. How genetic and non-genetic determinants of telomere length maintenance interact - with each other and other cancer etiologies - requires future research.