Faculty Summaries
Greg H. Enders, MD, PhD
Greg H. Enders, MD, PhD
Associate Professor
Greg.Enders@fccc.edu
Office Phone: 215-214-3956
Fax: 215-728-4333
Office: W225
  • Overview of Research Interests

    Studies in the Enders lab focus on the role of Cyclin dependent kinases (Cdks) in mammalian cell cycle control and tumorigenesis, with emphasis on gastrointestinal tumors. A second project addresses the mechanism of action of the tumor suppressor and Cdk inhibitor p16Ink4a. A third project was recently initiated with David Weinberg studying Barrett’s esophagus.

  • Cyclin A/Cdk2 Regulation of Mitotic Entry
    Changqing Li & Tina Chen
    Dominant negative mutation in Cdk2
    Dominant negative mutation in Cdk2

    Through conditional induction of a dominant negative mutant of Cdk2 and RNAi directed against cyclin A, we have obtained evidence that cyclin A/Cdk2 complexes drive activation of cyclin B/Cdk1 complexes and mitotic entry. We are delineating the molecular events that are involved, including inactivation of the Cdk inhibitory kinase Wee1. Wee1 appears to be recognized as a cyclin A/Cdk2 substrate. These studies have provided insights for a revised model of mitotic entry in mammalian cells.

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  • Inhibition of Colon Tumorigenesis by p16Ink4a
    Amelie Boquoi
    Intestinal tumor in p16-null mouse
    Intestinal tumor in p16-null mouse

    We have shown that expression of p16 in tissue culture results in a cell cycle block that evolves over several days into senescence. We are now studying whether p16 imposes senescence during its function as a tumor suppressor in the intestine, a major site of action. p16 is expressed in a subset of non-neoplastic and neoplastic colon cells with properties of stem cells. Cells with high level expression appear to be arrested. We have crossed mice carrying the Min (multiple intestinal neoplasia) mutation to Ink4a-knockout mice (defective in p16) and observed increased growth and vascularity of colon tumors, associated with higher levels of vascular endothelial growth factor (VEGF), confirming a tumor suppressor role for p16 in colon. We have generated new mouse transgenic models with enhanced expression of VEGF in the intestine. These mice display a thickened, hypercellular intestinal mucosa, with recruitment of mesenchymal cells and enhanced neoplasia. Thus, we are studying whether and how p16 imposes senescence in this physiologic setting of function, acts within stem cells, and mediates key effects on paracrine signaling.

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  • Cell Cycle Markers in Barrett’s Esophagus
    Urs von Holzen

    We have recently initiated a project with David Weinberg studying Barrett’s esophagus. Barrett’s is an important pre-malignant metaplasia in which the normal squamous epithelium is replaced by an intestinal-like columnar epithelium. Disease progression is associated with DNA damage and p16 inactivation. We are prospectively collecting tissue from Barrett’s patients and analyzing markers of the DNA damage checkpoint response and associated cell cycle delays. We seek to better understand the pathogenesis of the disease and identify markers of cancer risk of potential clinical utility.

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