Paula J. Bates, Ph.D.

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:

Professor, Department of Medicine, University of Louisville School of Medicine
Director, UofL-ExCITE Hub, an NIH REACH (Research Evaluation And Commercialization Hub) site
Member and Co-Leader, Experimental Therapeutics & Diagnostics Program, 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
Fellow, National Academy of Inventors

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 G-quadruplex structures that bind 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. Recent collaborative projects in our laboratory have focused on the activity and mechanism of several synthetic and plant-derived small molecules with antiproliferative effects (e.g. copper complexes, XB05, plagiochiline, and physangulidine). In addition to pursuing basic and translational research, I am interested in developing programs that increase research commercialization and entrepreneurship in academia. I am the director of the UofL-ExCITE product development hub, which is one of only 3 sites in the nation selected by NIH to establish their Research Evaluation And Commercialization Hub (REACH) network. The  goal of REACH is to increase the number of university-derived technologies that are translated into real-world products by providing proof-of-concept funding, education, and mentoring. As ExCITE director, I have overseen the evaluation of >150 technologies and management of 19 product development grants. Our ExCITE portfolio includes diverse technology types (therapeutic, vaccine, device, diagnostic, eHealth) that aim to tackle a wide range of health-related problems including cancer, heart disease, ulcerative colitis, eye pain, antibiotic-resistant bacteria, blood shortages, infant feeding issues, and speech therapy adherence.

Representative Publications:

Research Commercialization and Drug Discovery/ Development

Bates PJ*, Fabel D, Rubin CT, Gurvich VT, Muscoplat CC.  NIH program strives to turn more lab discoveries into real-world treatments. https://www.statnews.com/2017/04/17/nih-reach-biomedicine-treatments/. STAT News 2017 (Boston Globe Media).

Bates PJ*, Reyes-Reyes EM, Malik MT, Murphy EM, O'Toole MG, Trent JO.  G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms.  Biochimica et Biophysica Acta General Subjects 2017 May;1861(5 Pt B):1414-28. PMID: 28007579. PMCID: pending.

Malik MT*, O'Toole MG, Casson LK, Thomas SD, Bardi GT, Reyes-Reyes EM, Ng CK, Kang KA, Bates PJ*.  AS1411-conjugated gold nanospheres and their potential for breast cancer therapy.  Oncotarget 2015 Sep 8;6(26):22270–81. PMID: 26045302. PMCID: PMC4673162.

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.  Experimental & Molecular Pathology 2009 Jun;86(3):151-63. PMID: 19454272. PMCID: PMC2716701. (*corresponding author)

 

Discovery/ Mechanism of AS1411, an Antiproliferative G-rich Oligonucleotide and Nucleolin Aptamer

Reyes-Reyes EM, Šalipur FR, Shams M, Forsthoefel MK, Bates PJ*.  Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.  Molecular Oncology 2015 Aug;9(7):1392-405. PMID: 25911416. PMCID: PMC4523413.

Reyes-Reyes EM, Teng Y, Bates PJ*.  A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin–dependent mechanism.  Cancer Research 2010 Nov 1;70(21):8617-29. PMID: 20861190. PMCID: PMC2970734.

Teng Y, Girvan AC, Casson LK, Thomas SD, Pierce WM, Qian M, Bates PJ*.  AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin.  Cancer Research 2007 Nov 1;67(21):10491-500. PMID: 17974993. [ http://cancerres.aacrjournals.org/content/67/21/10491.long ]

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.  Molecular Cancer Therapeutics 2006 Jul;5(7):1790-99. PMID: 16891465. [ http://mct.aacrjournals.org/content/5/7/1790.long ]

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.  Journal of Biological Chemistry 2001 Nov 16;276(46):43221-30. PMID: 11555643. [ http://www.jbc.org/content/276/46/43221.long ]

Bates PJ, Kahlon JB, Thomas SD, Trent JO, Miller DM.  Antiproliferative activity of G-rich oligonucleotides correlates with protein binding.  Journal of Biological Chemistry 1999 Sep 10;274(27):26369-77. PMID: 10473594.[ http://www.jbc.org/content/274/37/26369.long ]

 

Discovery and Mechanism of Small Molecule Agents with Antiproliferative Activity

Stivers NS, Islam A, Reyes-Reyes EM, Casson LK, Aponte JC, Vaisberg AJ, Hammond GB, Bates PJ*.  Plagiochiline A inhibits cytokinetic abscission and induces cell death.  Molecules (Basel, Switzerland) 2018 Jun 12;23(6):1481. PMID: 29895732. [ http://www.mdpi.com/1420-3049/23/6/1418 ]

Salipur FR, Reyes-Reyes EM, Xu B, Hammond GB, Bates PJ*.  A novel small molecule that induces oxidative stress and selectively kills malignant cells.  Free Radical Biology & Medicine 2014 Mar;68:110-2. PMID: 24321317.

Reyes-Reyes EM, Jin Z, Vaisberg AJ, Hammond GB, Bates PJ*.  Physangulidine A, a withanolide from Physalis angulata, perturbs the cell cycle and induces cell death by apoptosis in prostate cancer cells. Journal of Natural Products 2013 Jan 25;76(1):2-7. PMID: 23270478.

 

Biophysical Studies of Quadruplex and Triplex DNA Oligonucleotides

Choi EW, Nayak LV, Bates PJ*.  Cancer-selective antiproliferative activity is a general property of some G-rich oligodeoxynucleotides.  Nucleic Acids Research 2010 Mar;38(5):1623-35. PMID: 20008101.  PMCID: PMC2836550.

Dailey MM, Miller MC, Bates PJ, Lane AN, Trent JO. Resolution and characterization of the structural polymorphism of a single quadruplex-forming sequence.  Nucleic Acids Research 2010 Aug;38(14):4877–88. PMID: 20348136. PMCID: PMC2919704.

Dapic V, Abdomerovic V, Marrington R, Peberdy J, Rodger A, Trent JO, Bates PJ*.  Biophysical and biological properties of quadruplex oligodeoxyribonucleotides Nucleic Acids Res. 2003 Apr 15;31(8):2097-107. PMID: 12682360. PMCID: PMC153744.

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 Research 1995 Sep 25;23(8):3627-32. PMID: 7478988. PMCID: PMC307257.

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 Research 1995 Nov 11;23(21):4283-9. PMID: 7501447. PMCID: PMC307381.

 

Nucleolin Biology

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.  Journal of Biological Chemistry 2003 Mar 7;278(10):8572-9. PMID: 12506112.

Farin K, Schokoroy S, Haklai R, Cohen–Or I, Elad–Sfadia G, Reyes-Reyes ME, Bates PJ, Cox AD, Kloog Y, Pinkas–Kramarski R.  Oncogenic synergism between ErbB1, nucleolin, and mutant Ras.  Cancer Research 2011 Mar 15;71(6):2140–51. PMID: 21257709. [ http://cancerres.aacrjournals.org/content/71/6/2140.long ]

PubMed Information