Paula J. Bates, Ph.D.
Associate Professor of Medicine and of Biochemistry & Scientist, Brown Cancer Center
Email Paula Bates
Phone Numbers: (502) 852 2432 (Office) & (502) 852 2354 (Lab)
Fax Number: (502) 852 2356
University of Louisville
CTRB - 409
509 South Hancock Street
Louisville, KY 40202, USA
Ph.D. 1996, University of London
- Scientist, James Graham Brown Cancer Center, University of Louisville
- Associate Professor, Department of Medicine
- Associate Professor, Division of Hematology/Oncology
- Associate Professor, Department of Biochemistry
Cancer, drug discovery, aptamers, nucleolin, cell biology, epigenetics
- E. Merit Reyes-Reyes, Ph.D. - Senior Research Associate
- Sarah A. Andres, Ph.D. - Postdoctoral Scholar
- Jaspreet Grewal, M.D. - Hematology-Oncology Fellow
My laboratory is researching a novel class of guanosine-rich oligonucleotides (GROs) that can inhibit proliferation and induce cell death in many types of cancer cells, whereas they have less effect on normal cells. One of these oligonucleotides (AGRO100, now known as AS1411) is currently being tested in human clinical trials and the results of the Phase I study are very encouraging. The GROs are capable of forming unusual structures known as G-quadruplexes and function as aptamers by binding to specific cellular proteins. I have identified the major target protein for these oligonucleotides as nucleolin, a multi-functional protein whose levels correlate with the rate of cell proliferation. Current studies concern mechanistic aspects of the observed anticancer effects, the relationship between oligonucleotide structure and activity, and the development of G-rich oligonucleotides as therapeutic agents. I am also examining the role of nucleolin in cancer cell biology and its potential as a novel target for cancer drug discovery, with the ultimate aim of developing new anticancer agents targeted to nucleolin. Other ongoing projects include the discovery of new tumor-targeting oligonucleotides, the identification of anticancer compounds from Amazonian rainforest plants, and the development of a novel inhibitor of DNA methylation.
- Girvan AC, Teng Y, Casson LK, Thomas SD, Jüliger S, Ball MW, Klein JB, Pierce WM, Barve SS and Bates PJ. AGRO100 Inhibits Activation of Nuclear Factor-kB (NF-kB) by Forming a Complex with NEMO and Nucleolin. Molecular Cancer Therapeutics 5, 1790-1799 (2006). PMID: 16891465
- Li J, Trent JO, Bates PJ and Ng CK. Labeling G-rich Oligonucleotides (GROs) with N-succinimidyl 4-[18F] Fluorobenzoate (S18FB). Journal Of Labelled Compounds and Radiopharmaceuticals 49, 1213-1221 (2007).
- Bates P, Mergy J-L, and Yang D. Quartets in G-major. EMBO Rep. 8, 1003-1010 (2007). PMID: 17901879
- Teng Y, Girvan AC, Casson LK, Thomas SD, Pierce WM, Qian M and Bates PJ. AS1411 Alters the Localization of a Complex containing Protein Arginine Methyltransferase 5 and Nucleolin. Cancer Research 67, 10491-10500 (2007). PMID: 17974993
- Li J, Trent JO, Bates PJ and Ng CK (2009). Factors affecting the Labeling Yield of F-18-labeled AS1411. Journal Of Labelled Compounds and Radiopharmaceuticals 50, 1255-1259 (2009).
- Bates PJ, Laber DA, Miller DM, Thomas SD, and Trent JO. Discovery and Development of the G-rich Oligonucleotide AS1411 as a Novel Treatment for Cancer. Exp. Mol. Pathol. 86, 151-163 (2009). PMID: 19454272
- Aponte JC, Yang H, Vaisberg AJ, Castillo D, Málaga E, Verástegui M, Casson LK, Stivers N, Bates PJ, Rojas R, Fernandez I, Lewis WH, Sarasara C, Sauvain M, Gilman RH, and Hammond GB. Cytotoxic and anti-infective sesquiterpenes present in Plagiochila disticha (Plagiochilaceae) and Ambrosia peruviana (Asteraceae). Planta Med 76, 705-707 (2010). PMID: 19960415
- Choi EW, Nayak LV and Bates PJ. Cancer-selective antiproliferative activity is a general property of some G-rich oligodeoxynucleotides. Nucleic Acids Res. 38, 1623-1635 (2010). PMID: 20008101
- Arumugam S, Miller MC, Maliekal J, Bates PJ, Trent JO, and Lane AN. Solution structure of the RBD1,2 domains from human nucleolin. J Biomol NMR 47, 79-83 (2010). PMID: 20376532
- Dailey MM, Miller MC, Bates PJ, Lane AN, and Trent JO. Resolution and characterization of the structural polymorphism of a single quadruplex-forming sequence. Nucleic Acids Res 38, 4877-4888 (2010). PMID: 20348136
- Reyes-Reyes EM, Teng Y, and Bates PJ. A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism. Cancer Res., 70, 8617-8629 (2010). PMID: 20861190
- Farin K, Schokoroy S, Haklai R, Cohen-Or I, Elad-Sfadia G, Reyes-Reyes ME, Bates PJ, Cox AD, Kloog Y, and Pinkas-Kramarski R. Oncogenic synergism between ErbB1, nucleolin, and mutant Ras. Cancer Res. 71, 2140-2151 (2011). PMID: 21257709
- 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
- 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. Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells. PLoS One 7, e38278 (2012). PMID: 22693611
- Reyes-Reyes EM, Jin Z, Vaisberg AJ, Hammond GB, and Bates PJ. 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 (2013).
- Li J, Zheng H, Bates PJ, Malik MT, Liu XF, Trent JO, and Ng CK. Aptamer Imaging with Cu-64 Labeled AS1411: Preliminary Assessment in Lung Cancer. Nuclear Med. Biol., article accepted for publication (2013).
Patents & Licenses:
- Miller DM, Bates PJ and Trent JO. "Antiproliferative activity of G-rich oligonucleotides and method of using the same to bind to nucleolin" (issued US patent 7,314,926, published US patent applications 20080318890, 20080318897, 20080318898 and 20080318899).
- Bates PJ, Miller DM, Trent JO and Xu X. "Method for the diagnosis and prognosis of malignant diseases" (issued US patents 7,347,928 and 7,541,150, published US patent applications 20030194754, 20050053607 and 20090017009).
- Bates PJ and Mi YC. "A method for detection of apoptosis" (published US patent application 20040132049).
- Bates PJ, Girvan AC and Barve SS. "Methods for the detection and treatment of inflammatory conditions" (published US patent application 20050187176).
- Hammond GB, Xu B and Bates PJ. “Therapeutic Compounds” (published US patent application 20080188570).
- Bates PJ and Choi EW. “Methods and products to target, capture, and characterize stem cells” (filed patent application December 2007).
- Hammond GB, Xu B, Liu L and Bates PJ. “Novel gold compounds” (filed patent application December 2008).
- Reyes-Reyes EM and Bates PJ. Methods of increasing macropinocytosis in cancer cells. Provisional application filed March 2010.
- Islam MA and Bates PJ. Treatment of VHL-negative tumors. Provisional application filed April 2010.
- Bates PJ, Malik MT, and Rinaldo FM. “Predictive Markers of Therapeutic Efficacy” (filed patent application[s] March 2011)
- Bates PJ, Malik MT, and Kang KA. “Anti-Nucleolin Conjugated Nanoparticles” (filed patent application[s] June 2012)
- Salipur FR, Bates PJ, Hammond GB, and Xu B. “Compositions And Methods For Inhibiting DNMT1 Inhibitor Cytotoxicity” (filed patent application[s] September 2012)
- Hammond GB, Jin Z, Bates PJ, Reyes-Reyes EM, and Vaisberg A. “Compounds, Compositions, Pharmaceutical Compositions, And Methods Of Use” (filed patent application[s] November 2012)