Hartmut (Hucky) Land
Ph.D. 1982 University of Heidelberg
Robert and Dorothy Markin Professor and Chair, Department of Biomedical Genetics (BMG)
Director of Research and Co-Director, James P. Wilmot Cancer Center
Director, Genetics Program
Cooperation of oncogenic mutations in the control of malignancy
* Understand the molecular basis for oncogene cooperation
* Identify unique features of gene networks in cancer cells vs. normal cells
* Exploit such features of cancer cells for targeted approaches towards therapeutic intervention
* Systems biology of cancer cells
Carcinogenesis is a process driven by multiple co-operating oncogenic mutations in which features of the cancer cell phenotype, such as proliferative advantage, only emerge as a result of the interplay between these mutations. This is consistent with the notion that many divergent cancers share a limited number of disease mechanisms with common underlying signaling networks, despite the many genes implicated in the disease.
The Land laboratory has pioneered investigation of the nature and underlying principles of cancer gene cooperation originating with the discovery that multiple oncogenic mutations are required for malignant cell transformation. Using a wide variety of experimental approaches, including genomics and systems biology, the laboratory has demonstrated that the cooperation of cancer-promoting genetic lesions is strongly reflected by synergistic modulation in signaling and the gene networks of malignant cells.
Recently, the laboratory has identified molecular events downstream of cooperating oncogenic mutations that are critical to cell transformation (McMurray et al., 2008). Using genomic approaches, approximately 100 genes that alter their expression synergistically in response to the combined effect of two oncogenic mutations were identified. Importantly, the regulation of these ‘cooperation response genes’ (CRG) is critical for the cancer phenotype at surprisingly high frequency, indicating that oncogenic mutations cooperate through synergistic regulation of downstream gene networks. CRGs control diverse cellular processes, such as cell signaling, survival, motility, invasiveness and self-renewal, thus indicating how cooperating oncogenic mutations ultimately affect multiple parallel cancer cell traits. Several research projects that focus on the nature of cancer cells as highly integrated systems are being pursued (see also below).
- Critical role of cooperation response genes (CRGs) for the cancer phenotype
- The cancer phenotype is controlled by a network of CRGs
- CRG expression profiles as indicators for drug efficacy and mechanism
McMurray, H.R., Sampson, E. R., Compitello, G., Kinsey, C., Newman, L., Smith, B., Chen, S., Klebanov, L., Salzman, P, Yakovlev, A and Land, H. (2008) Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype. Nature, 453:1112-1116. View article in PubMed.
Xia, M. and Land, H. (2007) Tumor suppressor p53 restricts Ras stimulation of RhoA and cancer cell motility. Nature Structural & Molecular Biology 14:215-223. View article in PubMed.
Klebanov, L., Gordon, A., Xiao, Y., Land, H. and Yakovlev, A. (2005) A permutation test motivated by microarray data analysis. Computational Statistics and Data Analysis, 50:3619-3628.
Graduate Program Affiliations
University of Rochester
601 Elmwood Ave.
Rochester, NY 14642
Office: MRB 2-9633