OHSU

R. Michael Liskay, Ph.D.

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Background

We use yeast and mice to study DNA mismatch repair (MMR), which corrects mismatches and senses DNA damage. MMR gene mutations increase spontaneous mutation and predispose to hereditary and sporadic cancer. Using gene targeting strategies, we derive and study knockout mice for four MutL homologs, Mlh1, Pms1 or Pms2, and Mlh3. We have observed increased mutation and cancer risk in these animals, although the severity varies between the different knockouts. In a related project, we have developed an assay using the site-specific recombinase Cre to stochastically inactivate tumor suppressor genes or activate oncogenes in the mouse. The system also uses a color marker (B-galactosidase) which is activated by the recombinase thus marking those cell lineages experiencing inactivation (or activation) of the "loxp"-tagged tumor suppressors/oncogenes. One question being addressed is "What is the minimum number of cancer gene alterations that are sufficient to promote intestinal tumor formation and progression in the mouse?" Our studies in yeast are centered on a better understanding of the mechanism and gene products involved in DNA mismatch repair.


Selected Publications

"Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention," Carcinogenesis (Vol: 35, Issue: 1, Page 237-246) - 2014

"Different phenotypic consequences of simultaneous versus stepwise Apc loss," Oncogene (Vol: 31, Issue: 16, Page 2028-2038) - 2012

"Conservation of functional asymmetry in the mammalian MutLα ATPase," DNA Repair (Vol: 9, Issue: 11, Page 1209-1213) - 2010

"Embryonic lethality after combined inactivation of Fancd2 and Mlh1 in Mice," Cancer Research (Vol: 69, Issue: 24, Page 9431-9438) - 2009

"Tractable Cre-lox system for stochastic alteration of genes in mice," Nature Methods (Vol: 5, Issue: 3, Page 227-229) - 2008

 

Contact

  Email R. Liskay

503 494-3475

Memberships & Associations

American Association for the Advancement of Science (Fellow), Genetics Society of America.