Inappropriate activation of a single enzyme, telomerase, is associated with the uncontrolled proliferation of cells seen in as many as 90 percent of all human cancers. Since the mid-1990s, when telomerase was first identified in human tumors, scientists have eyed the enzyme as an ideal target for developing broadly effective anti-cancer drugs. The important role of telomerase in cancer makes this enzyme an important drug target. I propose a structural biology approach to examine the function of telomerase and its role in human disease. Structural data can prove invaluable in explaining, as well as designing, biochemical and biophysical experiments. It can also be a very powerful tool for drug discovery. The long-term goal of my research plan is to use structural biology, in conjunction with biochemistry to understand how telomerase replicates telomere ends, and to apply this information to the pursuit of anti-cancer therapies.

Public Health Relevance

Telomerase has been implicated in cancer, cardiovascular disease and aging. For this reason, our goal is to elucidate the biological function of this enzyme and use this information to combat cancer and age-related diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM088332-04
Application #
8478133
Study Section
Macromolecular Structure and Function C Study Section (MSFC)
Program Officer
Preusch, Peter C
Project Start
2010-06-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$320,424
Indirect Cost
$134,131
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Harkisheimer, Michael; Mason, Mark; Shuvaeva, Elena et al. (2013) A motif in the vertebrate telomerase N-terminal linker of TERT contributes to RNA binding and telomerase activity and processivity. Structure 21:1870-8
Bryan, Christopher; Rice, Cory; Harkisheimer, Michael et al. (2013) Structure of the human telomeric Stn1-Ten1 capping complex. PLoS One 8:e66756