Email Paula Bates
Phone Numbers: (502) 852 2432 (Office) & (502) 852 2354 (Lab)
Fax Number: (502) 852 2356
Address:
University of Louisville
321B Delia B. Baxter Research Building
580 South Preston Street
Louisville, KY 40202, USA
Ph.D. 1996, University of London

Additional Appointments:

•  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

Research Interests:

Cancer, drug discovery, aptamers, nucleolin, cell biology, epigenetics

Investigators:

• Lavona Casson, B.S. - Research Assistant
• Enid Choi, B.S. - Graduate Student (MD/PhD program)
• M. Ashraf Islam Ph.D. - Senior Research Associate
• M. Tariq Malik, Ph.D. - Postdoctoral Fellow
• E. Merit Reyes-Reyes, Ph.D. - Senior Research Associate
• Francesca Rinaldo, B.S. - Graduate Student (MD/PhD program)
• Mitra Shams, M.D. - Visiting Researcher
• Nicole Stivers - Undergraduate Student
• Yun Teng, Ph.D. - Postdoctoral Fellow

Research Interests:

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.

Selected Publications:

1. 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, Hammond GB (2010). Cytotoxic and anti-infective sesquiterpenes present in Plagiochila disticha (Plagiochilaceae) and Ambrosia peruviana (Asteraceae). Planta Med 76, 705-707.
   
2. Choi EW, Nayak LV, Bates PJ (2010). Cancer-selective antiproliferative activity is a  general property of some G-rich oligodeoxynucleotides. Nucleic Acids Res. 38, 1623-1635.
   
3. Dailey MM, Miller MC, Bates PJ, Lane AN, Trent JO (2010). Resolution and characterization of the structural polymorphism of a single quadruplex-forming sequence. Nucleic Acids Res 38, 4877-4888.
4. Arumugam S, Miller MC, Maliekal J, Bates PJ, Trent JO, Lane AN (2010). Solution structure of the RBD1,2 domains from human nucleolin. J Biomol NMR 47, 79-83.
   
5. Reyes-Reyes EM, Teng Y, Bates PJ (2010). A new paradigm for aptamer therapeutic AS1411 action: Uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism. Cancer Research (in press).
6. Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO (2009). Discovery and Development of the G-rich Oligonucleotide AS1411 as a Novel Treatment for Cancer. Exp. Mol. Pathol. 86, 151-164.   
7. Li J, Trent JO, Bates PJ and Ng CK (2007). Factors affecting the Labeling Yield of F-18-labeled AS1411. Journal Of Labelled Compounds and Radiopharmaceuticals 50, 1255-1259.
8. 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 Research 67, 10491-10500.
9. Bates P, Mergy J-L, Yang D (2007). Quartets in G-major. EMBO Rep 8, 1003-1010.
10. Li J, Trent JO, Bates PJ and Ng CK (2007). Labeling G-rich Oligonucleotides (GROs) with N-succinimidyl 4-[18F] Fluorobenzoate (S18FB). Journal Of Labelled Compounds and Radiopharmaceuticals 49, 1213-1221.
11. 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).
12. McMicken HW, Bates PJ and Chen Y. Antiproliferative activity of G- quartet-containing oligonucleotides generated by a novel single-stranded DNA expression system. Cancer Gene Therapy 10, 867-869 (2003).
13. Dapic V, Abdomerovic V, Marrington R, Peberdy J, Rodger A, Trent JO and Bates PJ. Biophysical and biological properties of quadruplex oligonucleotides. Nucleic Acids Res. 31, 2097-2107 (2003).
14. Mi Y, Thomas SD, Xu X, Casson LK, Miller DM, and Bates PJ. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J. Biol. Chem. 278, 8572-8579 (2003).
15. Dapic V, Bates PJ, Rodger A, Trent JO and Miller DM. Antiproliferative activity of G-rich oligonucleotides with backbone and sugar modifications. Biochemistry 41, 3676-3685 (2002).
16. Xu X, Thomas SD, Burke TJ, Girvan AC, McGregor WM, Trent JO, Miller DM and Bates PJ. Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. J. Biol. Chem. 276, 43221-43230 (2001).

Selected Abstracts:

1. Teng Y, Pierce WM, Bates PJ. Proteomic studies of nucleolin complexes in prostate cancer cells treated with novel anticancer agent, AS1411. Proceedings of the American Association of Cancer Research 98th Annual Meeting (April 2007).
2. Soleimani-Meigooni DN, Mi Y, Thomas SD, Jenson AB, Bates PJ. Uncoupling of cell growth and division: An unusual mechanism of non-apoptotic cell death in leukemia cells treated with novel anticancer aptamer, AS1411. Proceedings of the American Association of Cancer Research 98th Annual Meeting (April 2007).
3. Bates PJ, Hammond GB, Xu B, Aponte JC, Malik MT, Martin AN, Choi EW, Thomas SD, Casson LK, Trent JO. Discovery of XB05, a potent antiproliferative agent and novel non-nucleoside inhibitor of DNA methyltransferase 1. Proceedings of the American Association of Cancer Research 2008 Annual Meeting (April 2008).
4. Malik MT, Martin AN, Choi EW, Thomas SD, Casson LK, Trent JO, Xu B, Hammond GB, Bates PJ. XB05: A novel non-nucleoside inhibitor of DNMT1 with potent activity in colon, breast and prostate cancer cells. Proceedings of the American Association of Cancer Research 2008 Annual Meeting (April 2008).
5. Nayak LV, Choi EW, Casson LK, Thomas SD, Bates PJ. Identification of potential tumor-targeting aptamers using SELEX. Proceedings of the American Association of Cancer Research 2008 Annual Meeting (April 2008).
6. Choi EW, LV Nayak NV, Bates PJ. G-rich oligodeoxynucleotide libraries have selective antiproliferative effects on cancer cells. Proceedings of the American Association of Cancer Research 2009 Annual Meeting (April 2009).
7. Nicole S. Stivers, Ashraful Islam, Lavona K. Casson, Jose C. Aponte, Gerald B. Hammond, Abraham J. Vaisberg, and Paula J. Bates. Plagiochiline A blocks cytokinesis. Proceedings of the American Association of Cancer Research 2010 Annual Meeting (April 2010).
8. E. Merit Reyes-Reyes and Paula J. Bates. A new paradigm for AS1411 activity: Uptake by macropinocytosis and induction of macropinocytosis by a nucleolin-dependent mechanism. Proceedings of the American Association of Cancer Research 2010 Annual Meeting (April 2010).
9. M. Tariq Malik, Francesca Rinaldo, Mitra Shams, Lavona K. Casson, Wolfgang Zacharias, Sabine Waigel, Vennila Arumugam, Nazarul Hasan, Chuan Hu, Bo Xu, Gerald B. Hammond, and Paula J. Bates. A novel inhibitor of DNA methylation. Proceedings of the American Association of Cancer Research 2010 Annual Meeting (April 2010).
10. Ashraful Islam, David Jones, Fiona McLaughlin, and Paula J. Bates. Differential response to AS1411 in a pair of VHL-positive and VHL-negative renal carcinoma cell lines. Proceedings of the American Association of Cancer Research 2010 Annual Meeting (April 2010).
11. Yun Teng, David Jones, Fiona McLaughlin, and Paula J. Bates. AS1411 causes a specific increase in levels of cell surface nucleolin in responsive cell lines. Proceedings of the American Association of Cancer Research 2010 Annual Meeting (April 2010).
    

Patents & Licenses:

1. 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).
2. 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).
3. Bates PJ and Mi YC. "A method for detection of apoptosis" (published US patent application 20040132049).
4. Bates PJ, Girvan AC and Barve SS. "Methods for the detection and treatment of inflammatory conditions" (published US patent application 20050187176).
5. Hammond GB, Xu B and Bates PJ. “Therapeutic Compounds” (published US patent application 20080188570).
6. Bates PJ and Choi EW. “Methods and products to target, capture, and characterize stem cells” (filed patent application December 2007).
7. Hammond GB, Xu B, Liu L and Bates PJ. “Novel gold compounds” (filed patent application December 2008).
8. Reyes-Reyes EM and Bates PJ. Methods of increasing macropinocytosis in cancer cells. Provisional application filed March 2010.
9. Islam MA and Bates PJ. Treatment of VHL-negative tumors. Provisional application filed April 2010.