Associate Professor, Department of Internal Medicine, Gastroenterology & Hepatology
University of Nebraska Medical Center
685870 Nebraska Medical Center
Omaha, NE 68198-5870
University of Texas Southwestern Medical Center, Dallas, TX, Post-doctoral, 1999 Université de Montréal, Montreal, Canada, PhD in Biochemistry, 1991
Université de Montréal, Montreal, Canada, BS in Biochemistry, 1984
Areas of Interest
My laboratory is focused on two separate aspects of cancer research: the biology of telomeres and telomerase and the biochemistry of the Kras/Rac1 pathway. In the context of pancreatic cancer cells, my laboratory is studying the role of these systems in the development of the tumors and their potential value as therapeutic targets for the treatment of the disease. Telomerase is responsible for the maintenance of telomeres, which are specialized structures that cap and protect the ends of chromosomes. Because most human cells lack telomerase, telomeres shorten each time cells divide and this shortening limits the lifespan of normal human cells. During cancer development, this obstacle to infinite proliferation is almost always overcome by the aberrant reexpression of telomerase. To limit the lifespan of pancreatic cancer cells, my laboratory is testing novel strategies to block telomerase in cancer cells. Pancreatic cancer development is initiated by the acquisition of oncogenic mutations in the Kras gene, which causes activation of the Kras GTPase and of its downstream effectors. Among the critical pathways activated by these mutations in pancreatic cancer cells is a Kras/Rac1/YAP pathway, which we have now shown plays a critical role in the malignant transformation, long-term survival, and therapeutic responses of pancreatic tumor cells. In collaboration with other groups, we are developing drugs that block this pathway for the treatment of pancreatic cancer.
Burchett KM, Etekpo A, Batra SK, Yan Y, and Ouellette MM (2017) Inhibitors of telomerase and poly(ADP-ribose)polymerases synergize to limit the lifespan of pancreatic cancer cells. Oncotarget 8: 83754-767. PMCID: PMC5663552
Arnst JL, Hein AL, Taylor MA, Palermo NY, Contreras JI, Sonawane YA, Wahl AO, Ouellette MM, Natarajan A, and Yan Y (2017) Discovery and characterization of small molecule Rac1 inhibitors. Oncotarget 8: 34586-600. PMCID: PMC5470993
Choi KH, Lakamp-Hawley AS, Kolar C, Yan Y, Borgstahl GEO, and Ouellette MM (2015) The Oligonucleotide/Oligosaccharide Binding fold 1 (OB1) of human POT1 recognizes both telomeric and non-telomeric DNA motifs. Biochimie 115: 17-25. PMCID: PMC4500675.
Yan Y, Hein AL, Etekpo A, Burchett KM, Lin C, Enke CA, Batra SK, Cowan KH, and Ouellette MM (2014) Inhibition of RAC1 GTPase sensitizes pancreatic cancer cells to gamma-irradiation. Oncotarget 5: 10251-70. PMCID: PMC4279370
Burchett KM, Yan Y, and Ouellette MM (2014) Telomerase inhibitor Imetelstat (GRN163L) limits the lifespan of pancreatic cancer cells. PLoS One 9: e85155. PMCID: PMC3883701.