Paula J. Bates, PhD


Associate Professor, Department of Medicine; Scientist, James Graham Brown Cancer Center

Research Program
Molecular Targets

Education
B.A. (Honors), Queens College, Univesrity of Oxford, UK, Chemistry, 1992
Ph.D., Institue of Cancer Research, University of London, Biophysics, 1996

Postdoctoral Fellow, University of Alabama at Birmingham, USA, 1996 - 1999

Research and Professional Experience

1996 - 1999
Postdoctoral Fellow, Department of Medicine, Division of Hematology & Oncology, University of Alabama at Birmingham
 
1999 - 2005
Assistant Professor (Tenure Track), Department of Medicine, Division of Hematology & Oncology, University of Louisville

2000 - 2005
Assistant Professor of Biochemistry and Molecular Biology (Join Apppointment), University of Louisville

1999 - present
Scientist, James Graham Brown Cancer Center, University of Louisville

2001 - 2005
Co-founder and Vice President for Research, Aptamera, Inc. Louisville, KY (acquired by Antisoma, p.l.c. in February 2005)

2005 - present
Consultant, Antisoma p.l.c., London

2005 - present
Associate Professor, Departments of Medicine and Biochemistry & Molecular Biology, University of Louisville

Selected Awards and Professional Honors

1991
Bursar's Award for Academic Studies, The Queen's College, University of Oxford

1997 - present
Member, American Association for Cancer Research

1999
Finalist, Joseph Reeves Award for Excellence in Research by a Postdoctoral Scholar, Department of Medicine, University of Alabama at Birmingham

2000 - present
Member, Institute for Molecular Diversity and Drug Design (IMD3)

2000
Winner, Research of Most Scientific Importance, Faculty Research Day, Research! Louisville, University of Louisville

2001
Study Section Member, Cancer Molecular Target Drug Discovery Special Emphasis Panel, National Cancer Institute

2003
Named as one of “21 Women to Watch”,
Louisville magazine

2004
Mint Jubilee Outstanding Scientist of the Year Award, Louisville, KY

2004
Study Section Member, Molecular Genetics and Biology #5, Department of Defense Breast Cancer Research Program

2004
Winner, Faculty Research Day, Research with Greatest Potential for Major Clinical Applications, Research!Louisville, University of Louisville

2004 - present
Member, Editorial Board, Journal of Molecular Medicine

2005, 2006
Grant Reviewer, Concept Awards, Department of Defense Breast Cancer Program

Research Interest
My laboratory is researching a novel class of guanosine-rich oligonucleotides 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.  The G-rich oligonucleotides 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 these oligonucleotides as therapeutic agents. I also am 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.

Publications
Bates PJ, Dosanjh HS, Kumar S, Jenkins TC, Laughton CA, Neidle S.  Detection and kinetic studies of triplex formation by oligodeoxynucleotides using real-time biomolecular interaction analysis (BIA). Nucleic Acids Res 23:3627-32, 1995

Bates PJ, Macaulay VM, McLean MJ, Jenkins TC, Reszka AP, Laughton CA, Neidle S.  Characteristics of triplex-directed photoadduct formation by psoralen-linked oligodeoxynucleotides. Nucleic Acids Res 23:4283-9,1995

Macaulay VM, Bates PJ, McLean MJ, Rowlands MG, Jenkins TC, Ashworth A, Neidle S.  Inhibition of aromatase expression by a psoralen-linked triplex-forming oligonucleotide targeted to a coding sequence. FEBS Lett 372:222-8, 1995

Bates PJ, Laughton CA, Jenkins TC, Capaldi DC, Roselt PD, Reese CB, Neidle S. Efficient triple helix formation by oligodeoxyribonucleotides containing alpha- or beta-2-amino-5-(2-deoxy-D-ribofuranosyl) pyridine residues. Nucleic Acids Res 24:4176-84,1996

Blume SW, Lebowitz J, Zacharias W, Guarcello V, Mayfield CA, Ebbinghaus SW, Bates P, Jones DE, Trent JO, Vigneswaren N, Miller DM.  The integral divalent cation within the intermolecular purine*purine. pyrimidine structure. Nucleic Acids Res 27:695-702, 1999

Cogan DZM, Howarth IS, Bates PJ, Robinson A, Rodger A. “DNA binding of ruthenium tris(1,10-
phenanthroline). Inorganic Chemistry 38:4486-97, 1999

Bates PJ, Kahlon JB, Thomas SD, Trent JO, Miller DM.  Antiproliferative activity of G-rich oligonucleotides correlates with protein binding. J Biol Chem 274:26369-77, 1999

Xu X, Thomas SD, Burke TJ, Girvan AC, McGregor WM, Trent JO, Miller DM, Bates PJ.  Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. J Biol Chem 276:43221-30, 2001

Rodger A, Norden B, Rodger PM, Bates PJ.  DNA as a catalyst and catalytic template for the racemisation of metal tris-phenanthroline complexes. Eur J Inorg Chem 1:49-53, 2002

Dapic V, Bates PJ, Rodger A, Trent JO, Miller DM. Antiproliferative activity of G-rich oligonucleotides with modified backbones. Biochemistry 41:3676-85, 2002

Bates PJ, Reddoch JF, Hansakul P, Arrow A, Dale R, Miller DM.  Biosensor detection of triplex formation by modified oligonucleotides.  Anal Biochem 307:235-43, 2002

Inge TH, Casson LK, Priebe W, Trent JO, Georgeson KE, Miller DM, Bates PJ.  Importance of Sp1 consensus motifs in the MYCN promoter. Surgery 132:232-8, 2002

Mi Y, Thomas SD, Xu X, Casson LK, Miller DM, Bates PJ. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J Biol Chem 278:8572-9, 2003

Dapic V, Abdomerovic V, Marrington R, Peberdy J, Rodger A, Trent JO, Bates PJ. Biophysical and biological properties of quadruplex oligodeoxyribonucleotides Nucleic Acids Res 31:2097-107, 2003

McMicken HW, Bates PJ, Chen Y. Antiproliferative activity of G-quartet-containing oligonucleotides generated by a novel single-stranded DNA expression system. Cancer Gene Therapy 10:867-9. 2003

Kutsch O, Levy DN, Bates PJ, Decker J, Kosloff BR, Shaw GM, Priebe W, Benveniste EN. Bis-Anthracycline antibiotics inhibit HIV-1 transcription. Antimicrob Agents Chemother 48:1652-63, 2004


Girvan AC, Teng Y, Casson LK, Thomas SD, Jüliger S, Ball MW, Klein JB, Pierce WM, Barve SS, Bates PJ.  AGRO100 inhibits activation of nuclear factor-kB (NF-kB) by forming a complex with NEMO and Nucleolin.  Molec Cancer Therap 5:1790-9, 2006

Teng Y, Girvan AC, Casson LK, Pierce WM Jr, Qian M, Thomas SD, Bates PJ.  AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin.  Cancer Res 67(21):10491-500, 2007

Bates PJ, Choi EW, Nayak LV.  G-rich oligonucleotides for cancer treatment.  Methods Mol Biol 542:379-92, 2009

 

Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO.  Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer.  Exp Mol Pathol 86(3):151-64, 2009; PMC2716701.  Review.

Contact Information

CTR Building
505 South Hancock Street
Louisville, KY 40202
(502) 852-2432



Fax: (502) 852-2356