Dr. Liu's research focuses on developing new mouse models or using existing mouse models to study the genes or pathways that are important in telomere length maintenance and genomic stability or that contribute to genomic instability, cell death, and malignancies when disrupted.

Loss of genomic stability is the hallmark of cancer. Loss of genetic material at chromosome ends ("telomere shortening") contributes to genomic instability that leads to cell death or cancer development. Telomere integrity in cells thus plays an essential role in the control of genomic stability. Accumulating evidence suggests that telomere integrity depends on the ability to maintain telomere length and/or the ability to mask the telomeres from being recognized as damaged DNA. However, the mechanisms by which short telomeres lose their capacity to suppress DNA damage responses are not well understood.

Previously while working at the Amgen Research Institute/Ontario Cancer Institute, Canada, Dr. Liu has established the mouse and mouse embryonic stem (ES) cells deficient in telomerase activity. Using a combination of molecular, genetic and biochemical analyses, Dr. Liu's lab will continue to study the genes or pathways that contribute to genomic instability and cell apoptosis in telomerase deficient mice or ES cells with critically short telomeres. In addition, Dr. Liu's lab will establish new mouse models, which carry N-ethyl-N-nitrosourea (ENU)-induced mutations in specific genes that are important in telomere length maintenance or genomic stability. These mouse models are wonderful genetic tools to study RNA-protein or protein-protein interactions in the telomerase complex, which is critical in our understanding of the telomerase complex and its function. The fact that telomere length maintenance and telomerase complex is evolutionarily conserved may allow us to extend these findings to humans by providing therapeutic targets that may reduce cell viability in cancer cells.

• Gomez M, Schreiber V, Wu J, Dunlap J, Dantzer F, Wang Y, and Liu Y. PARP1 is a TRF2-associated poly(ADP-ribose)polymerase and protects eroded telomeres. Molecular Biology of the Cell, in press.
• Hsiao J. Susan, Poitras F. Marc, Cook D. Brandoch, Liu Y. Smith S. Tankyrase 2-PARP domain deleted mice are runt, but have normal telomere length and capping. Molecular and Cellular Biology, in press.
• Campbell M, Wang Y, Andrew S, Liu Y. Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect. Oncogene, Dec 5, 2005.
• Wang Y, Erdmann N, Giannone J. R, Wu J, Liu Y. An increase in telomere sister chromatid exchange in murine embryonic stem cells and murine splenocytes possessing critically shortened telomeres. Proc Natl Acad Sci, 102:10256-10260, 2005.
• Wang Y, Giannone R, and Liu Y. Telomere sister chromatid exchange in telomerase deficient murine cells. Cell Cycle, 4:1320-2. 2005.
• Price J.R, Aykac D, Gleason S. S, Chourey K, Liu Y. Quantitative comparison of mitotic spindles by confocal image analysis. Journal of Biomedical Optics, Oct, 2005.
• Cho H.P, Liu Y, Gomez M, Dunlap J, Tyers M, Wang Y. The phosphatase cdc14B boundless and stabilizes microtubules. Molecular and Cellular Biology, 25:4541-51, 2005.
• Liu, Y., Snow B., Zhou W., Kickhoefer V.A., Erdmann N., Wakeham A., Gomez M., Harrington L. A vault protein, VPARP, is associated with mammalian telomerase and is dispensable in telomerase function and vault structure in vivo. Molecular and Cellular Biology, 24: 5314-5323., 2004
• Erdmann, N., Liu, Y., Harrington L. Progressive haploinsufficiency in mTert +/- mice leads to accelerated sterility in mTert -/- mice. Proceedings of the National Academy of Sciences 101: 6080-6085, 2004
• Liu, Y., Kha, H., Ungrin, M., Robinson, M.O., Harrington L. Preferential maintenance of critically short telomeres in mammalian cells heterozygous for mTert. Proceedings of the National Academy of Sciences, 99: 3597-3602, 2002.
• Liu, Y., Snow, B., Hande, M.P., Baerlocher, G., Yeung, D., Wakeham, D. Itie, A., Siderovski, D., Landsdorp, P.M., Robinson, M.O., Harrington L. The telomerase-associated protein TEP1 is not essential for telomerase activity or telomere length maintenance in vivo. Molecular and Cellular Biology, 20:8178-8184, 2000.
• Liu, Y., Snow, B., Hande, M.P., Yeung, D., Erdmann. N.J., Wakeham, D., Itie, A., Siderovski, D., Landsdorp, P.M., Robinson, M.O., Harrington, L. The Telomerase Reverse Transcriptase Is Limiting and Necessary for Telomerase Function in vivo. Current Biology, 10:1459-1462, 2000.
• Kickhoefer, V.A., Liu, Y., Snow, B., Kong, L., Zhou, W., Robinson, M.O., Stewart, P.L., Harrington, L., Rome, L.H. The telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle. Journal of Cell Biology, 152: 157-164, 2001.
• Merup, M., Jansson, M., Corcoran, M., Liu, Y., Wu, X., Rasool, O., Stellan, B., Hermansson, M., Juliusson, G., Gahrton, G., Einhorn, S. A FISH cosmid 'cocktail' for detection of 13q deletions in chronic lymphocytic leukaemia--comparison with cytogenetics and Southern hybridization. Leukemia, 12:705-9, 1998.
• Merup, M., Moreno, T.C., Heyman, M., Ronnberg, K., Grander. D., Detlofsson, R., Rasool, O., Liu, Y., Soderhall, S., Juliusson, G., Gahrton. G., Einhorn, S. 6q deletions in acute lymphoblastic leukemia and non-Hodgkin's lymphomas. Blood, 91;3397-400, 1998.
• Li, C., Larsson, C., Eutreal, A., Lancaster, J., Phelan, C., Aspenblad, U., Sundelin, B., Liu, Y., Ekman, P., Auer, G., Bergerheim, U. BRCA2 and RB1 are not the targets of 13q deletions in prostate cancer: evidence of putative tumor suppressor genes near RB1 and DAM. Oncogene, 16:481-487, 1998.
• Corcoran, M., Rasool, O., Liu, Y., Iyengar, A., Grander, D., Ibbotson, R.E., Merup, M., Wu, X., Brodyansky, V., Gardiner, A.C., Juliusson, G., Chapman, R.M., Ivanova, G., Tiller, M., Gahrton, G., Yankovsky, N., Zabarovsky, E., Oscier, D.G., Einhorn, S. Detailed molecular delineation of 13q14.3 loss in B-cell chronic lymphocytic leukemia. Blood, 91:382-90, 1998.

• Kapanadze, B.I., Brodianskii, V.M., Semov, A.B., Baranova, A.V., Sulimova, G.E., Aitova, S.S., Udina, I.G., Ptitsyna, S.N., Sal'nikova, L.E., Chudinov, O.S., Borbiev, T.E., Kashuba, V.V. Gizatullin, R., Zabarovskaia, V., Zabarovskii, E.R., Fedorova, L.I., Zelenin, A.V., L'iu, I., Rasul, O., Einkhorn, S., van Everdink, W., van den Berg, A., Buys, C., Corcoran, M., Iankovskii, N.K. Cosmid contig and cDNA map of the 13q14 region is frequently deleted in human B-cell chronic lymphocytic leukemia. Molecular Biology (Mosk), 3:515-519, 1997.
• Imreh, S., Kost-Alimova, M., Kholodnyuk, I., Yang, Y., Szeles, A., Kiss, H., Liu, Y., Foster, K., Zavarovsky, E., Stanbridge, E., Klein, G. Differential Elimination of 3p and retention of 3q segments in human/mouse microcell hybrids during tumor growth. Genes, Chromosomes, and Cancer, 20:224-233, 1997.
• Liu, Y., Corcoran, M., Rasool, O., Ivanova, G., Ibbotson, R., Grander, D., Iyengar, A., Baranova, A., Kashuba, V., Merup, M., Wu, X., Gardiner, A., Mullenbach, R., Poltaraus, A., Hultstrom, A.L., Juliusson, G., Chapman, R., Tiller, M., Cotter, F., Gahrton, G., Yankovsky, E., Zabarovsky, E., Einhorn, S., Oscier, D. Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia. Oncogene, 15:2463-2473, 1997.
• Heyman M, Moreno RC, Liu Y, Ronnback K, Grander D, Rasool O, Borgonova-Brandter L, Soderhall S, Einhorn S. Inverse correlation between loss of heterozygosity of the short arm of chromosome 12 and p15ink4b and p16ink4 gene inactivation in acute lymphoblastic leukaemia. British Journal of Haematology, 98: 147-150, 1997.
• Wu X, Merup M, Juliusson G, Jansson M, Stellan B, Grander D, Zabarovsky E, Liu Y, Spasokoukotskaja T, Gahrton G, Einhorn S. Characterization of a hairy cell leukemia-associated 5q13.3 inversion breakpoint. Genes Chromosomes and Cancer, 20:337-346, 1997.
• Heyman M, Nordgren A, Teherani M, Rasool O, Liu Y, Grandir D, Ost E, Wallberg B, Johansson B, Einhorn S. A T-cell acute lymphocytic leukemia patient with two malignant cell populations carrying different deletions of the p16 gene. Response to interferon-a therapy in one of the subclones. Leukemia, 10: 909-917, 1996.
• Heyman M, Rasool O, Brandter L, Liu Y, Grander D, Soderhall S, Einhorn S. "Exclusive" p15ink4b gene deletions in acute lymphocytic leukemia include the E1ßexon of the p16ink4 gene. Blood, 87:1657-1658, 1996.
• Heyman M, Rasool O, Brandter L, Liu Y, Grander D, Soderhall S, Gustavsson G, Einhorn S. Prognostic importance of p15ink4b and p16ink4 gene inactivation in childhood acute lymphocytic leukemia. Journal of Clinical Oncology, 14:1512-1520, 1996.
• Brandter L, Heyman M, Rasool O, Liu Y, Grander D, Einhorn S. p16ink4 inactivation is a frequent event in malignant T-cell lines. European Journal of Haematology, 56:313-318, 1996.
• Rasool O, Heyman M, Brandter L, Liu Y, Grander D, Soderhall S, Einhorn S. p15ink4B and p16ink4 gene inactivation in acute lymphocytic leukemia. Blood, 85: 3431-3436, 1995.
• Liu, Y. Genetic changes on human chromosome 13. Thesis. ISBN 91-628-1555-5, 1995.
• Liu, Y., Rasool, O., Grander, D., Lindbrvm, A., Einhorn, S. Sequence variability of a prolonged tetranucleotide repeat. Human Molecular Genetics, 4:727-729, 1995.
• Liu, Y., Hermanson, M., Grander, D., Merup, M., Wu, S., Heyman, M., Rasool, O., Juliusson, J., Gahrton, G., Detlofsson, R., Nikiforova, N., Buys, C., Soderhall, C., Yankovsky, N., Zabarovsky, E., Einhorn, S. 13q deletions in lymphoid malignancies. Blood, 86:1911-1915, 1995.
• Heyman M, Grander D, Brondum-Nielsen K, Cederblad B, Liu Y, Xu B, Einhorn S. Interferon system defects in malignant T-cells. Leukemia, 8:425-434, 1994.
• Heyman M, Grander D, Liu Y, Brondum-Nielsen K, Soderhall S, Einhorn S. Functional studies on T-cell lines with or without deletions of interferon genes. Leukemia, 8: 425-434, 1994.
• Liu, Y., Soderhall, S., Heyman, M., Gtrander, D., Brondum-Nielsen, K., Einhorn, S. Multiple genetic events involving RB1 gene deletion and amplification of chromosome 21 in a case of acute lymphocytic leukemia. Genes, Chromosomes, and Cancer, 9:72-75, 1994.
• Liu, Y., Heyman, M., Wang, Y., Falkmer, U., Hising, C., Szekely, L., Einhorn, S. Molecular analysis of the retinoblastoma gene in primary ovarian cancer cells. International Journal of Cancer, 58: 663-667, 1994.
• Liu, Y., Szekely, L., Grander, D., Soderhall, S., Juliusson, G., Gahrton, G., Linder, S., Einhorn, S. Chronic lymphocytic leukemia cells with allelic deletions at13q14 commonly have one intact RB1 gene. Evidence for a role of an adjacent locus. Proceedings of the National Academy of Sciences, 90: 8697-8701, 1993.
• Heyman M, Grander D, Brondum-Nielsen K, Liu Y, Soderhall S, Einhorn S. Deletions of the short arm of chromosome 9, including the interferon-genes, in acute lymphocytic leukemia. Studies on loss of heterozygosity, parental origin of deleted genes and prognosis. International Journal of Cancer, 54: 748-753, 1993.
• Juliuson G, Gahrton G, Einhorn S, Liu Y, Oscier DF, Chapman R. Chromosome abnormalities and RB1 gene deletions in chronic lymphocytic leukemia. Blood, 82:1938-1939, 1993.
• Grander D, Heyman M, Brondum-Nielsen K, Liu Y, Lundgren E, Soderhall S, Einhorn S. The interferon system in primary acute lymphocytic leukemia cells with or without deletions of the interferon genes. Blood, 79: 2076-2983, 1992.
• Liu, Y., Grander, D., Soderhall, S., Juliusson, G., Gahrton, G., Einhorn, S. Retinoblastoma gene deletions in B-cell chronic lymphocytic leukemia. Genes, Chromosomes, and Cancer, 4: 250-256, 1992.