Research Programs

 

 

Program Activities and Selected Scientific Reports

  • Regular monthly meetings, grand rounds & invited speakers
  • Shared resource review and leadership
  • Participation in organ site oncology programs
2013 Selected Scientific Progress & Achievements

The role of c-Myc in cancer has been a focus of Michael Cole’s work since the 1980’s, when he identified this gene as activated by translocation to immunoglobulin regulatory elements in plasmacytoma. Recently, his work in collaboration with Jason Moore (CEC) has turned to exploit genome-wide association studies (GWAS) data to identify sequence nucleotide polymorphisms in breast, prostate, and colorectal cancer that may influence a patient’s risk.

Dr. Radu Stan has a long-standing interest in endothelial cell biology that has led him to study the role of a cellsurface receptor, PV1, in a capillary structure called fenestrae. His program interactions recently led to SBIR proposals to commercialize blocking antibodies for applications in cancer.

Work integrating angiogenesis/tumor microenvironment, melanoma (both laboratory-based models and clinical), immunology, and gene expression expertise has elucidated mechanisms of matrix metalloproteinase (MMPs) regulation and its role in tumor heterogeneity and progression (Croteua 2013).

New computational methods (Dr. Cheng) have led to collaborations with the Ernst Lab (Artinger et al PNAS, 2013) and the Whitfield lab (Cheng et al PlosGenetics, 2013) to reveal transcriptional factor networks underlying cancers under investigation.

A very significant body of basic to translational work has come from interprogrammatic collaborations between Dragnev, Dmitrovsky, Ahmed, DiRenzo and Memoli. Initially this work focused on animal models of lung cancer in which cyclin E was over-expressed and/or resistant to degradation. From this work, several mechanistic insights and avenues for therapy were discovered. Significantly, this work has extended into the clinic through work of Dr. Dragnev with input by Dr. Memoli (Ma et al, 2013), who showed that bexarotene could target cyclinD for degradation and, in conjunction with the EGFR inhibitor erlotinib, potentially could synergistically act to reduce cyclinD and cell survival.

2012 Selected Scientific Accomplishments
  • Discovery of a new modulator of Wnt pathway signaling related to a molecule affected in myotonic dystrophy patients; this finding represents a new molecular target to influence Wnt-signaling in cancer (Xin N, et al., 2011).
    • Xin N, Benchabane H, Tian A, Nguyen K, Klofas L, Ahmed Y (2011). Erect Wing facilitates context-dependent Wnt/Wingless signaling by recruiting the cell-specific Armadillo-TCF adaptor Earthbound to chromatin. Development 138(22):4955-4967. PMC3201663
  • Identification of molecules and processes governing the polarity of cell division (Anker JF, et al., 2011).
    • Anker JF, Gladfelter AS (2011). Axl2 integrates polarity establishment, maintenance, and environmental stress response in the filamentous fungus Ashbya gossypii. Eukaryot Cell 10(12):1679-1693. PMC3232731
  • Discovery of a p53-Id2 tumor suppressor pathway in neural progenitor cells (Paollela BR, et al., 2012).
    • Paolella BR, Havrda MC, Mantani A, Wray CM, Zhang Z, Israel MA (2011). p53 directly represses Id2 to inhibit the proliferation of neural progenitor cells. Stem Cells 29(7):1090-1101.
  • Development of a microRNA approach to reprogram dendritic cells to combat ovarian cancer (Cubillos-Ruiz JR, et al., 2012).
    • Cubillos-Ruiz JR, Baird JR, Tesone AJ, Rutkowski MR, Scarlett UK, Camposeco-Jacobs AL, Anadon-Arnillas J, Harwood NM, Korc M, Fiering SN, Sempere LF, Conejo-Garcia JR (2012). Reprogramming tumor-associated dendritic cells in vivo using microRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res 72(7):1683-1693. PMC3319850
  • Inter-programmatic work elucidating a retinoic acid-dependent step in the effector T cell and anti-tumor cytolytic T cell differentiation process (Guo Y, et al., 2012 and Piño-Lagos, et al., 2012).
    • Pino-Lagos K, Guo Y, Brown C, Alexander MP, Elgueta R, Bennett KA, De Vries V, Nowak E, Blomhoff R, Sockanathan S, Chandraratna RA, Dmitrovsky E, Noelle RJ (2011). A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity. J Exp Med 208(9):1767-1775. PMC3171100
  • Discovery of a role for Mad2 in stabilizing kinetochore-microtubule attachments in mitosis (Kabeche L, et al., 2012).
    • Kabeche L, Compton DA (2012). Checkpoint-independent stabilization of kinetochoremicrotubule attachments by Mad2 in human cells. Curr Biol 22(7):638-644. PMC3326208
  • Elucidation of a Myc-HIF1 pathway in cancer (Doe M, et al., 2012)
    • Doe MR, Ascano JM, Kaur M, Cole MD (2012). Myc posttranscriptionally induces HIF1 protein and target gene expression in normal and cancer cells. Cancer Res 72(4):949-957. PMC3288382 [Available on 2013/2/15]
  • Inter-programmatic study resulting in the identification of UBP43 as an anti-cancer target (Guo Y, et al., 2012).
    • Guo Y, Chinyengetere F, Dolinko AV, Lopez-Aguiar A, Lu Y, Galimberti F, Ma T, Feng Q, Sekula D, Freemantle SJ, Andrew AS, Memoli VA, Dmitrovsky E (2012, In press). Evidence for the Ubiquitin Protease UBP43 as an antineoplastic target. Mol Cancer Ther
  • Collaborative discovery of a Polo-like-kinase mechanism to ensure chromosome segregation (Hood EA, et al., 2012).
    • Hood EA, Kettenbach AN, Gerber SA, Compton DA (2012). Plk1 regulates the kinesin-13 protein Kif2b to promote faithful chromosome segregation. Mol Biol Cell 23(12):2264-2274. PMC Journal - In Process