Paula J. Bates, Ph.D.

Education:

B.A., Chemistry, University of Oxford, England, 1992
Ph.D., Biophysics, University of London, England, 1996
Postdoctoral Fellowship, University of Alabama at Birmingham, Birmingham, AL, 1996–1999

Curriculum Vitae

Current Positions:

Associate Professor, Department of Medicine, University of Louisville School of Medicine
Member, James Graham Brown Cancer Center
Member, Institute for Molecular Diversity and Drug Design, University of Louisville
Associate Member, Department of Biochemistry and Molecular Biology, University of Louisville
Associate Member, Department of Pediatrics, University of Louisville

Contact Information:

Clinical Translational Research Building, Room 409
University of Louisville
505 Hancock St.
Louisville, KY 40202, USA
Phone 502-852-2432
Fax 502-852-3661
Email: paula.bates@louisville.edu

Research Description:

The overarching theme of my group’s research is the development of novel and selective anticancer agents. A major focus in my laboratory is the use of DNA aptamers (protein-binding oligonucleotides) for cancer therapy. In particular, I was involved in the discovery and bench-to-bedside translation of a G-rich DNA aptamer named AS1411 (now ACT-GRO-777, previously AGRO100), which became the first anticancer aptamer to be tested in human clinical trials. AS1411 folds into a G-quadruplex structure that binds to nucleolin (a protein present at high levels on the surface of cancer cells) and can kill cancer cells without harming non-malignant cells. Ongoing basic research related to AS1411 aims to better understand the molecular mechanisms responsible for its cancer-selective effects and unusual ability to get inside cells. AS1411 has also been widely used around the world as a tool to investigate the biological functions of nucleolin and as a cancer-targeting ligand to deliver diverse attached cargoes selectively to tumors. Currently, we are developing various AS1411-linked nanoparticles for use in cancer therapy, drug delivery, and imaging. Other recent projects in our laboratory have focused on the activity and mechanism of various synthetic and plant-derived small molecules with antiproliferative effects. Of these, a small molecule named XB05 is of particular interest because of its potential for translation to the clinic: XB05-like molecules have cancer-selective cytotoxicity, a novel mechanism of action (disruption of redox homeostasis), proven in vivo efficacy with no acute toxicity in mouse models, and an associated candidate biomarker that predicts cancer cell response to XB05. In addition to pursuing basic and translational research, I am interested in developing programs to increase research commercialization and entrepreneurship in academia.

Literature Cited:

  1. Salipur FR, Reyes-Reyes EM, Xu B, Hammond GB, and Bates PJ (2014). A Novel Small Molecule that Induces Oxidative Stress and Selectively Kills Malignant Cells. Free Radic. Biol. Med. 68, 110-121. PMID: 24321317
  2. Reyes-Reyes EM, Jin Z, Vaisberg AJ, Hammond GB, and Bates PJ (2013). Physangulidine A, a withanolide from Physalis angulata, perturbs the cell cycle and induces cell death by apoptosis in prostate cancer cells. J. Nat. Prod.76, 2-7. PMID: 23270478
  3. Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, Pierce WM Jr, Ivanova MM, Bates PJ, Appana SN, Datta S, Kulesza P, McBryan J, Young LS, and Klinge CM (2012). Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells. PLoS One7, e38278. PMID: 22693611. PMCID: PMC3365040
  4. Jin Z, Mashuta MS, Stolowich NJ, Vaisberg AJ, Stivers NS, Bates PJ, Lewis WH, and Hammond GB. Physangulidines A, B, and C: three new antiproliferative withanolides from Physalis angulata L. Org. Lett. 14, 1230–1233 (2012). PMID: 22329497
  5. Farin K, Schokoroy S, Haklai R, Cohen-Or I, Elad-Sfadia G, Reyes-Reyes EM, Bates PJ, Cox AD, Kloog Y, and Pinkas-Kramarski R (2011). Oncogenic synergism between ErbB1, nucleolin, and mutant Ras. Cancer Research71, 2140-2151. PMID: 21257709
  6. Reyes-Reyes EM, Teng Y, and Bates PJ (2010). A new paradigm for aptamer therapeutic AS1411 action: Uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism. Cancer Research 70, 8617-8629. PMID: 20861190. PMCID: PMC2970734
  7. Dailey MM, Miller MC, Bates PJ, Lane AN, and Trent JO (2010). Resolution and characterization of the structural polymorphism of a single quadruplex-forming sequence. Nucleic Acids Res. 38, 4877-4888. PMID: 20348136. PMCID: PMC2919704
  8. Bates PJ, Laber DA, Miller DM, Thomas SD, and Trent JO (2009). Discovery and Development of the G-rich Oligonucleotide AS1411 as a Novel Treatment for Cancer. Exp. Mol. Pathol. 86, 151-163 (2009). PMID: 19454272. PMCID: PMC2716701
  9. Teng Y, Girvan AC, Casson LK, Thomas SD, Pierce WM, Qian M and Bates PJ (2007). AS1411 Alters the Localization of a Complex containing Protein Arginine Methyltransferase 5 and Nucleolin. Cancer Research67, 10491-10500. PMID: 17974993

10.  Bates P, Mergy J-L, and Yang D (2007). Quartets in G-major. EMBO Rep. 8, 1003-1010. PMID: 17901879. PMCID: PMC2247389

11.  Girvan AC, Teng Y, Casson LK, Thomas SD, Jüliger S, Ball MW, Klein JB, Pierce WM, Barve SS and Bates PJ (2006). AGRO100 Inhibits Activation of Nuclear Factor-kB (NF-kB) by Forming a Complex with NEMO and Nucleolin. Molecular Cancer Therapeutics5, 1790-1799. PMID: 16891465

12.  Dapic V, Abdomerovic V, Marrington R, Peberdy J, Rodger A, Trent JO, and Bates PJ (2003). Biophysical and biological properties of quadruplex oligodeoxyribonucleotides Nucleic Acids Res.31, 2097-2107. PMID: 12682360. PMCID: PMC153744

13.  Mi Y, Thomas SD, Xu X, Casson LK, Miller DM, and Bates PJ (2003). Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J. Biol. Chem. 278, 8572-8579. PMID: 12506112

14.  Xu X, Thomas SD, Burke TJ, Girvan AC, McGregor WM, Trent JO, Miller DM and Bates PJ (2001). Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. J. Biol. Chem.276, 43221-43230. PMID: 11555643

15.  Bates PJ, Kahlon JB, Thomas SD, Trent JO and Miller DM (1999). Antiproliferative activity of G-rich oligonucleotides correlates with protein binding. J. Biol. Chem.274, 26369-26377. PMID: 10473594

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