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Toren Finkel, M.D., Ph.D.

Laboratory of Molecular Biology

Toren Finkel, M.D., Ph.D.
Senior Investigator
Laboratory of Molecular Biology


Building 10-CRC Room 5-3330
10 Center Dr
Bethesda, MD 20892
P: +1 301 402 4081
F: +1 301 402 0888
finkelt@nih.gov


Background

Toren Finkel received his undergraduate degree in physics from the University of Maryland before obtaining his M.D. and Ph.D. from Harvard Medical School in 1986. He completed his internship and residency training in internal medicine at the Massachusetts General Hospital in Boston, followed by a fellowship in cardiology at Johns Hopkins Medical School. In 1992, upon completion of this clinical training, he joined the NHLBI as an Investigator in the Cardiology Branch. He is a former Senior Scholar of the Ellison Medical Foundation. Dr. Finkel is the author or coauthor of more than 100 publications. He serves as the editor-in chief of Drug Discovery Today: Disease Mechanisms and is also an editor or editorial board member of Aging Cell, Mechanisms of Ageing and Development, Antioxidants and Redox Signaling, Molecular Aspects of Medicine, and IUBMB Life. Additionally is a member of the Nature Reviews Molecular Cell Biology Highlights Advisory Panel. He was inducted into American Society of Clinical Research in 2002 and into the Association of American Physicians in 2009.

Research Interests

Dr. Finkel’s research is focused on the role of cellular metabolism and oxidative stress in aging and age-related diseases. He became interested in oxidative stress through an early, counterintuitive discovery that hydrogen peroxide—a reactive oxygen species (ROS)—could act as an intracellular signaling molecule activated by certain growth factors. An interest in aging and metabolism has led to four related research avenues in his laboratory: oxidative homeostasis in stem cell biology; the use of cellular senescence as a model for aging; autophagy in aging and age-related diseases; and interrogating pathways identified in lower organisms to understand their role in mammalian aging.

Evidence suggests the need for tight regulation of oxidative homeostasis within stem and progenitor cell compartments. Dr. Finkel’s laboratory is testing this concept in mouse models through conditional or whole-body knockout of candidate genes. He and his colleagues recently found that mice lacking the polycomb repressor Bmi1 not only have defects in hematopoietic stem cell renewal, but also have impaired mitochondrial function and a marked increase in the intracellular levels of reactive oxygen species. This led to an accompanying increase in DNA damage that could be partially rescued through antioxidant treatment.

The connection between cellular senescence and organismal aging is not necessarily straightforward. Dr. Finkel’s laboratory is exploring the use of cellular senescence as a platform for discovery of mechanisms at play in the processes of aging and age-related diseases. He and his colleagues have developed a model—mouse embryonic fibroblasts deficient in the breast cancer-related gene BRCA1—that exhibits rapid senescence. By studying genetic deletions that could rescue the phenotype, they have found that deletion of 53BP1, a gene involved in non-homologous end joining, not only rescues senescence in BRCA1-deficient fibroblasts, but also enables development of a viable mouse without a cancer or aging phenotype.

Recycling of cellular components, mediated by autophagy, has been implicated in aging in lower organisms. In mouse models, Dr. Finkel’s laboratory has shown that sirtuins regulate autophagy. More recently, they demonstrated that the autophagy-related gene ATG7 can bind to the tumor suppressor protein p53. This molecular interaction links nutrient availability and autophagy to the regulation of the cell cycle. The laboratory is also investigating several other mouse models where autophagy has been inactivated within specific tissues. These studies are currently focused on the role of autophagy in the cardiovascular system.

Dr. Finkel and his colleagues are also studying genetic mouse models in which they extend lifespan by knocking out single genes. Using these mice, he is able to explore a more nuanced phenotype than a mere measure of lifespan to ask whether all age-related declines are affected uniformly. Is memory retained in older animals? Is bone density retained? So far, it appears that specific age-related pathways affect only a subset of age-related pathologies. Ultimately, Dr. Finkel believes that a better understanding of the molecular mechanisms of aging will have an impact on the treatment of a wide variety of age-related diseases.

Selected Publications

Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress.
Lee IH, Kawai Y, Fergusson MM, Rovira II, Bishop AJ, Motoyama N, Cao L, Finkel T.
Science. 2012 Apr 13;336(6078):225-8.
[Text Abstract on PubMed]

Bmi1 regulates mitochondrial function and the DNA damage response pathway.
Liu J, Cao L, Chen J, Song S, Lee IH, Quijano C, Liu H, Keyvanfar K, Chen H, Cao LY, Ahn BH, Kumar NG, Rovira II, Xu XL, van Lohuizen M, Motoyama N, Deng CX, Finkel T.
Nature. 2009 May 21;459(7245):387-92.
[Text Abstract on PubMed]

Augmented Wnt signaling in a mammalian model of accelerated aging.
Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, Malide D, Rovira II, Schimel D, Kuo CJ, Gutkind JS, Hwang PM, Finkel T.
Science. 2007 Aug 10;317(5839):803-6.
[Text Abstract on PubMed]

Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.
Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T.
N. Engl. J. Med. 2003 Feb 13;348(7):593-600.
[Text Abstract on PubMed]

Requirement for generation of H2O2 for platelet-derived growth factor signal transduction.
Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T.
Science. 1995 Oct 13;270(5234):296-9.
[Text Abstract on PubMed]

Toren Finkel's Full List of Publications

DIR News
March 12, 2014
Researchers find reason why many vein grafts fail
January 29, 2014
Correlative super-resolution fluorescence and transmission electron microscopyExternal link Disclaimer
December 23, 2013
President Obama honors outstanding early-career scientists
November 25, 2013
AAAS council elects 388 new AAAS FellowsExternal link Disclaimer
November 21, 2013
A new multilayer-based x-ray grating

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Last Updated: April 26, 2013

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