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.
Hasty P, Livi CB, Dodds SG, Jones D, Strong R, Javors M, Fischer KE,
Sloane L, Murthy K, Hubbard G, Sun L, Hurez V, Curiel TJ, Sharp ZD. eRapa restores a normal life span in a FAP mouse model. Cancer Prev Res (Phila). 2014 Jan;7(1):169-78.
Hu L, Kim TM, Son MY, Kim SA, Holland CL, Tateishi S, Kim DH, Yew PR, Montagna C, Dumitrache LC, Hasty P. Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes. Nature. 2013 Sep 26;501(7468):569-72.
Hasty P, Sharp ZD, Curiel TJ, Campisi J. mTORC1 and p53: clash of the gods? Cell Cycle. 2013 Jan 1;12(1):20-5.
Livi CB, Hardman RL, Christy BA, Dodds SG, Jones D, Williams C, Strong
R, Bokov A, Javors MA, Ikeno Y, Hubbard G, Hasty P, Sharp ZD. Rapamycin extends life span of Rb1+/- mice by inhibiting neuroendocrine tumors. Aging (Albany NY). 2013 Feb;5(2):100-10.
Kim TM, Rebel VI, Hasty P. Defining a genotoxic profile with mouse embryonic stem cells. Exp Biol Med (Maywood). 2013 Mar;238(3):285-93.