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Molecular and Cellular Biology

Houston, Texas

Image 1: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.; Image 2: By Yi LI, Ph.D.; Image 3: Mouse oocyte at meiosis I immunostained  for tubulin (red) phosphop38MAPK (green) and DNA (blue). By JoAnne Richards,  Ph.D.;  Image 4: Expanded cumulus cell ooctye ocmplex  immunostained for hyaluronan (red), TSG6 (green) and DAN (blue). By JoAnne  Richards, Ph.D.;  Image 5: Epithelial cells taken from a mouse  mammary gland were cultured in a dish and transduced with a retrovirus  expressing two genes. The green staining shows green fluorescent protein and the red  staining shows progesterone receptor expression. The nucleus of each cell is  stained blue. Photomicrograph taken at 200X magnification.  By Sandra L. Grimm,  Ph.D.; Image 6: Ovarian vasculature (red) is excluded from the granulosa cells (blue) within growing follicles (round structures); Image 7:  Ovulated mouse cumulus cell oocyte  complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.
Department of Molecular and Cellular Biology
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Nancy L. Weigel, Ph.D.

Professor
Department of Molecular and Cellular Biology

Education

Ph.D.: Johns Hopkins University, Baltimore
Postdoctoral training: Baylor College of Medicine, Houston

Research Interest

Steroid Receptors and Cell signaling in Prostate and Breast Cancer
The laboratory has three major research interests. The first is the regulation of progesterone receptor (PR), a ligand-activated transcription factor, by cell signaling pathways. We have found that cyclin A/Cdk2 (cyclin dependent kinase 2) is a novel PR coactivator and that cyclin dependent kinase is required for PR transcriptional activity. This provides a novel means of integrating the regulation of PR activity with cell cycle progression. Using a variety of approaches including mass spectrometry, we have found that there are 14 phosphorylation sites in PR We are utilizing a variety of functional analyses following site directed mutagenesis including microarrays and chromatin immunoprecipitation (ChIP) assays to identify the roles of these sites in target gene specific regulation of transcription. To determine the physiological roles of the sites, mouse models expressing phosphorylation site mutants will be used.

The second research area is to assess the role of androgen receptors in advanced prostate cancer. Androgen is a major growth stimulatory hormone in the prostate and androgen ablation is a key treatment for advanced prostate cancer. However, the tumors eventually become resistant to withdrawal of androgens and begin to re-grow. We are using novel approaches to identify androgen regulated genes and are evaluating the contributions of altered cell signaling and changes in coactivator/corepressor activity to the resistance to androgen ablation. Additional studies include an analysis of the molecular effects of clinically relevant cell signaling inhibitors on androgen receptor action.

The third research area is the analysis of the mechanism by which vitamin D inhibits the growth of prostate cancer cells. Our aims are to identify the immediate targets of vitamin D action using conventional approaches, microarray technology, and proteomics as well as to determine whether vitamin D or an analog can be used as a chemotherapeutic or chemopreventive agent in prostate cancer.

Contact Information

Baylor College of Medicine
One Baylor Plaza, Mail Stop: BCM130
Houston, TX 77030

Phone: 713-798-6234
E-mail: nweigel@bcm.edu

Selected Publications

  1. Washington MN, Kim JS, Weigel NL. (2010). 1alpha,25-dihydroxyvitamin D(3) inhibits C4-2 prostate cancer cell growth via a retinoblastoma protein (Rb)-independent G(1) arrest. Prostate. Jul 14. [Epub ahead of print] PubMed PMID: 20632309.
  2. Washington MN, Weigel NL. (2010). 1{alpha},25-Dihydroxyvitamin D3 Inhibits Growth of VCaP Prostate Cancer Cells Despite Inducing the Growth-Promoting TMPRSS2:ERG GeneFusion. Endocrinology 151:1409-17. PMID: 20147525.
  3. Phillips Rohan JN and Weigel NL. (2009). 1,25(OH)2D3 reduces c-Myc expression, inhibiting proliferation. Endocrinology 150(5):2046-54.
  4. Agoulnik IU and Weigel NL. (2009). Coactivator Selective Regulation of Androgen Receptor Activity. Steroids 74:669-674.
  5. Agoulnik IU, Bingman WE, Nakka M, Li W, Wang Q, Liu XS, Brown M, and Weigel NL. (2008). Target gene-specific regulation of androgen receptor activity by p42/p44 mitogen-activated protein kinase. Mol. Endocrinol. 22:2420-2432. PMID: 18787043.
  6. Weigel NL and Moore NL. (2007). Kinases and protein phosphorylation as regulators of steroid hormone action. Nucl Recept Signal. May 17;5:e005.
  7. Agoulnik IU, Vaid A, Nakka M, Alvarado M, Bingm an WE III, Erdem H, Frolov A, Smith CL, Ayala GE, Ittmann MM, and Weigel NL. (2006). Androgens Modulate Expression of TIF2, an Androgen Receptor Coactivator whose Expression Level Correlates with Early Biochemical Recurrence in Prostate Cancer. Cancer Research 66:10594-602.
  8. Proia DA, Nannenga BW, Donehower LA and Weigel NL. (2006). Dual Roles for the Phosphatase PPM1D in Regulating Progesterone Receptor (PR) Function. J. Biol. Chem. 281:7089-101.
  9. Agoulnik IU, Vaid A, Bingman WE III, Erdeme H, Frolov A, Smith CL, Ayala G, Ittmann MM, and Weigel NL. (2005). A Role for SRC-1 in Promoting Prostate Cancer Cell Growth and Tumor Progression. Cancer Research 65:7959-67.
  10. Narayanan R, Edwards DP, and Weigel NL. (2005). Human Progesterone Receptor Displays Cell Cycle Dependent Changes in Transcriptional Activity. Mol. Cell. Biol. 25:2885-98.

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