Associate Professor
Ph.D., University of Zurich, 2001

Cancer modeling and treatment; Senescence and tumor progression; cancer visualization; PTEN regulation

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Our research aims to define the causal events of tumor initiation in order to arrest cancers. To establish causality, we genetically model tumors in mice and validate our findings by comparative analysis with human cancers. In so doing, we have gained surprising insights into how tumorigenesis is prevented in tissues.

Generally, tumor suppressor genes were thought to allow cancer only when completely lost. We discovered that instead, loss of a single copy of the major tumor suppressor PTEN already results in tumor formation, while paradoxically, its complete loss triggers cells to senesce, resulting in a potent growth arrest that blocks development of cancer.

Thus, through stepwise modeling of tumor initiation in mice, we have learned that tumors need to progress in PTEN heterozygosity, a finding that for example is confirmed in the majority of human prostate cancers.

These findings govern two major areas of our research: (1) through understanding its regulation we aim to increase the remaining PTEN level in tumors to keep them benign; (2) through introducing additional patient-derived genetic alterations into Pten-mutant mice we define the set of genes that are necessary and sufficient for prostate cancer initiation and progression to metastasis. We are combining traditional gene targeting with in vivo RNA-interference methods and novel non-invasive cancer imaging technology. The combination of these approaches allows us to develop highly faithful and even patient-specific prostate cancer models. These in turn can be used to explore the therapeutic potential of novel drugs and of hairpin-mediated candidate gene-ablation by inducible RNAi-technology.

Please visit Lloyd's Lab home page.

Selected Publications

Trotman, L. 2008. Lloyd Trotman: of mice and men, cancer, and PTEN. Interviewed by Caitlin Sedwick.J. Cell Biol. 181: 402–403.

Trotman, L.C., Wang, X., Alimonti, A., Chen, Z., Teruya-Feldstein, J., Yang, H., Pavletich, N.P., Carver, B.S., Cordon-Cardo, C., Erdjument-Bromage, H., Tempst, P., Chi, S.G., Kim,H.J., Misteli, T., Jiang, X., and Pandolfi, P.P. 2007. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell 128: 141–156.

Trotman, L.C., Alimonti, A., Scaglioni, P.P., Koutcher, J.A., Cordon-Cardo, C., and Pandolfi,P.P. 2006. Identification of a tumor suppressor network opposing nuclear Akt function. Nature 441: 523–527.

Chen, Z., Trotman, L.C., Shaffer, D., Lin, H.K., Dotan, Z.A., Niki, M., Koutcher, J.A., Scher, H.I.,Ludwig, T., Gerald, W., Cordon-Cardo, C., and Pandolfi, P.P. 2005. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436: 725–730.

Trotman, L.C., Niki, M., Dotan, Z.A., Koutcher, J.A., Di Cristofano, A., Xiao, A., Khoo, A.S.,Roy-Burman, P., Greenberg, N.M., Van Dyke, T., Cordon-Cardo, C., and Pandolfi, P.P. 2003.Pten dose dictates cancer progression in the prostate. PLoS Biol. 1: 385–396.