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Our Science – LCP Website

Laboratory of Cancer Prevention

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Research

(For current overviews of our research from our 2005 Site Visit report - see the "Links" page.)

The Laboratory of Cancer Prevention (LCP) investigates the molecular basis of cellular processes that, when perturbed, can lead to cancer induction and progression. Discovery and characterization of molecular targets for cancer prevention and intervention is a common area of interest among the seven principal investigators in the LCP.

Members of the LCP are active in the NCI/CCR Cancer Prevention Faculty as well as in the Molecular Targets and the Cell Molecular Developmental Biology faculties. Collaborations with members of the Cancer Prevention Faculty aim to generate preclinical prevention outcomes that inform human clinical prevention trials.

The Gene Regulation Section (Nancy Colburn, Ph.D.) investigates gene regulation events that drive carcinogenesis and can be exploited for cancer prevention. Of particular interest is the activation of oncogenic transcription factors AP-1 and NFkB and of the novel tumor suppressing translation inhibitor Pdcd4. Mice genetically engineered for resistance to carcinogenesis are used to validate known targets and to discover new targets. Human cancer cell models are used to test applicability of molecular targeting for intervention in human disease.

The The Cancer Stem Cell Section (William L. Farrar, Ph.D.) studies genomic and epigenomic regulation in normal and cancer stem cell differentiation. Current focus is on understanding the role of inflammation in breast and prostate cancer stem cell development and in targeting these inflammatory processes for cancer prevention and intervention.

The Molecular Biology of Selenium Section (Dolph Hatfield, Ph.D.) studies how selenium enters proteins and how selenoproteins regulate cellular functions. Mouse models that are conditionally null for selenocysteinyl transfer RNA are used to assess the ability of selenoproteins to protect against breast, colon, and prostate cancer.

The Hematopoiesis and Stem Cell Biology Section (Jonathan R. Keller, Ph.D) studies the transcriptional regulation of stem cell quiescence, survival, self-renewal, and differentiation. We seek to understand how commitment to specific lineages is programmed and cell specific patterns of gene expression are established. Current studies are focused on defining the role of transcriptional regulators in myeloid cell development and their potential role in leukemogenesis.

The Epigenetics Group (Kathrin Muegge, M.D.) investigates heritable chromatin modifications that are crucial for normal embryogenesis. Using a mouse model that shows defects in genomic methylation and histone tail modifications they study the effects of perturbed chromatin structure on gene silencing, imprinting, mitosis and tumorigenesis. Understanding molecular pathways of chromatin modifications should lead to better targeting of epigenetic dysregulations occurring in cancer development.

The Retroviral Pathogenesis Section (Sandra Ruscetti, Ph.D.) studies the molecular basis of retroviral pathogenesis leading to leukemia or neurological disease. Understanding how deregulation of hematopoetic pathways can lead to leukemia is expected to aid in the design of rational strategies to counteract molecular events responsible for leukemia. Kinases such as PI-3 kinase, Akt, PKC, and JNK are of particular current interest.

This page was last updated on 7/2/2008.