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Sam & Ann Barshop Institute for Longevity and Aging Studies
Dr. E. Paul Hasty's lab focuses on the impact chromatin metabolism has on cancer and aging in genetically altered cells mice using embryonic stem cell/gene targeting technology.
Specifically, we study proteins important for the repair of DNA double - strand breaks by two different pathways. The first pathway is called recombinational repair by virtue that it utilizes a homologous template usually provided by the sister chromatid. To disrupt recombinational repair, we mutated Rad51 and found it to be essential for cellular proliferation and repair of DNA damaged by ionizing radiation. rad51 - mutant embryos die shortly after implantation.
Next, we determined that a cell cycle response contributed to embryonic lethality by crossing the rad51 - mutant mice to p53 - mutant mice. p53 is a tumor suppressor that is essential for stopping cellular proliferation after DNA damage. We also discovered that Rad51 functions by binding to a breast cancer susceptibility gene called Brca2 and mice with a subtle brca2 mutation exhibit a shortened life span due to increased cancer incidence.
Dr. E. Paul Hasty's lab focuses on the impact chromatin metabolism has on cancer and aging in genetically altered cells mice using embryonic stem cell/gene targeting technology.
Specifically, we study proteins important for the repair of DNA double - strand breaks by two different pathways. The first pathway is called recombinational repair by virtue that it utilizes a homologous template usually provided by the sister chromatid. To disrupt recombinational repair, we mutated Rad51 and found it to be essential for cellular proliferation and repair of DNA damaged by ionizing radiation. rad51 - mutant embryos die shortly after implantation.
Funding Agency NIH/NCI Title DNA Repair in Preventing MDS and AML after Radiation and Benzene Exposure Status Active Period 7/2012 - 6/2017 Role Principal Investigator Grant Detail The goal of this grant pertains to the role DNA repair has in suppressing MDS and AML in particular after exposure to environmental toxins, y-radiation and benzene.
Funding Agency March of Dimes Title Analysis of MmRad51 in tissue culture cells and mice Status Complete Period - Present Role Principal Investigator Grant Detail Grant was declined due to change from academic to industry position.
Hu L, Kim TM, Son MY, Kim SA, Holland CL, Tateishi S, Kim DH, Yew PR, Montagna C, Dumitrache LC, Hasty P, Hasty EP. Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes Nature 2013 Sep;501(7468):569-572. Maslov AY, Ganapathi S, Westerhof M, Quispe-Tintaya W, White RR, Van Houten B, Reiling E, Dolle ME, van Steeg H, Hasty EP, Hoeijmakers JH, Vijg J. DNA damage in normally and prematurely aged mice Aging Cell 2013 Jun;12:437-477. Dumitrache LC, Hu L, Son MY, Li H, Wesevich A, Scully R, Stark J, Hasty P. Trex2 enables spontaneous sister chromatid exchanges without facilitating DNA double-strand break repair Genetics 2011 Aug;188(4):787-797. Kim TM, Ko JH, Choi YJ, Hu L, Hasty P. The phenotype of FancB-mutant mouse embryonic stem cells Mutat Res 2011 Jul;712(1-2):20-27. Choi YJ, Son MY, Hasty P. One-step knockin for inducible expression in mouse embryonic stem cells Genesis 2011 Feb;49(2):92-97. Hasty P. Rapamycin: the cure for all that ails J Mol Cell Biol 2010 Feb;2(1):17-19.