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Chemistry

Faculty

Thomas Bannister, Ph.D.

Associate Scientific Director II
Assistant Professor of Medicinal Chemistry (Chemistry Dept.)
Translational Research Institute
Florida Campus
tbannist@scripps.edu
(561) 228-2206

Scripps Research Joint Appointments

Faculty, Graduate Program

Other Joint Appointments

Assistant Professor of Medicinal Chemistry, Department of Chemistry
Associate Scientific Director II

Research Focus

Organic/Medicinal Chemistry and Drug Discovery. The discovery of possible drug candidates is a highly collaborative endeavor, with medicinal chemistry as a core, problem-solving component.  Our major efforts are thus joint projects with world experts in cancer biology and neuroscience, wherein our group provides the organic and medicinal chemistry expertise. 

Our cancer projects target unique metabolic phenotypes of tumor cells, identifying defining molecular characteristics to be exploited for the development of targeted therapies. Most tumor types have a shared reliance upon active transport of nutrients and building blocks to drive rapid cancer cell growth and to sustain survival. They also largely rely upon glycolysis for ATP production (the Warburg effect). As examples, we have created molecules to keep tumor cells from exporting lactate, the end product of glycolysis.  We have also designed compounds to block amino acid transporters that are up-regulated by many tumors. Finally we have a program targeting expression of a transcription factor that drives colon cancer progression.

In our neuroscience studies we are developing GPCR agonists that have targeted effects in the brain, including a recently-identified tool compound with promise in an animal model of post-traumatic stress disorder (PTSD). We are also exploring GPCR signaling bias in opioid receptor activation, aiming for a holy grail of sorts: to separate the robust pain relief provided by opiates from their many unwanted side effects. This collaboration with Laura Bohn's group has led to pain relievers that seem to be devoid of many of the side effects of morphine and related opiates, such as respiratory suppression, heart rate effects, and GI effects (constipation).

Other exploratory efforts use medicinal chemistry in concert with high-throughput screening or following HTS campaigns, where we seek to discover and optimize "chemical probes", or first-in-class small molecules that should prove useful for investigating the therapeutic potential of new target proteins.  Such probe development efforts encompass multiple therapeutic areas, including treatments for cancers, glaucoma, ALS, Parkinson's Disease, addiction, infectious diseases, and mood disorders.  

One such chemical probe effort, a collaboration with Patsy McDonald, targets the orphan GPCR GPR151, a target that may be relevant for the development of treatments for addiction, depression, and schizophrenia.  In a collaboration with Sathya Puthanveettil we are investigating the potential of facilitating the function of kinesin motor proteins as a novel approach to therapies for Alzheimer’s disease (AD) and frontal temporal dementia (FTD), which are poorly-treated, common, and devastating disorders that increasingly burden world health care systems. In a collaboration with Corinne Lasmezas, we are developing compounds that rescue neurons from toxicity of protein aggregates, relevant for developing new therapies for ALS and Parkinson's Disease. Also, in a collaboration with Joe Kissil we are studying new antitumor agents that target the HIPPO-YAP pathway. In a collaboration with Kate Carroll we are modifying a natural product that targets the latent form of tuberculosis, which is currently not treatable. 

As you can tell, collaborative research is order of the day in my lab! Postdoctoral fellows in my group benefit from interactions not only with other chemists but with top biologists and pharmacologists, as they partake in project team meetings as well as in our weekly chemistry group meetings. My research is funded currently by 12 grants on which I am a principal investigator or investigator: R01DA035056, R01MH110441, R01CA172113, R01MH111116, R21NS093488, R01NS085223, R01DA038964, R01DK099090, R01DK103591, R01CA184277, R01AR066676, and R21A1119043.

On occasion I have openings for outstanding postdoctoral fellows in my labs.  Our postdoctoral scientists collaborate with a team of biological co-investigators, applying knowledge and experience in modern organic, heterocyclic, and/or medicinal chemistry toward an ongoing drug discovery effort. Excellent communication skills, good synthetic organic chemistry laboratory skills, ability to work in the US, and familiarity with modern synthetic techniques and instrumentation are required in this role.  Contact me for further details.

Education

A.B., chemistry, minors biology and mathematics, Summa Cum Laude, Wabash College, 1984
M.S., organic chemistry, Yale University, 1986
M.S., asymmetric synthesis, Yale University, 1987
Ph.D., natural products synthesis, Indiana University, 1991

Professional Experience

1991-1997: Marion Merrell Dow Pharmaceuticals (MMD) in Cincinnati, Ohio, a company subsequently renamed several times after mergers and acquisitions (Hoechst Marion Roussel, Aventis, Sanofi-Aventis, Sanofi, etc.). My work there included efforts to discover and develop agents for hypertension and congestive heart failure and also compounds to treat respiratory diseases and CNS disorders.

1997-2001: Sepracor Inc. in Marlborough, Massachusetts. At Sepracor, a company founded based upon chiral drug technologies, my work involved efforts to discover agents to treat drug-resistant bacterial infections, agents for pain relief, and compounds for use as antidepressants.

2002-2005: Daiichi Asubio LLC (aka “Daiamed”), in Cambridge, Massachusetts, a US subsidiary of Daiichi Pharmaceuticals,   I was a group leader in medicinal chemistry at where I worked toward the discovery of new anticoagulants and immunosuppressants.

2005-present: Scripps Florida, named Associate Director in the Translational Research Institute, a research unit aimed at drug discovery and managed by chemists and biologists with extensive experience in the pharmaceutical industry. At Scripps Florida, Success in obtaining grant funding as a Principal Investigator led to a full faculty appointment in 2010. 

Awards & Professional Activities

2008-2010: Member, Long Range Planning Committee (LRPC), Medicinal Chemistry Division of the ACS
2015: Chair, ACS Medicinal Chemistry Long Range Planning Committee (a nationally elected position)
2016: Chair, ACS Medicinal Chemistry Division (a nationally elected position)

Selected References

I have authored in total over 75 published patents and peer-reviewed journal articles related to drug discovery and medicinal/organic chemistry.  An on-line listing of most of my peer-reviewed pubmed-indexed journal publications can be found in the IN VIVO link above or also at: http://www.ncbi.nlm.nih.gov/sites/myncbi/thomas.bannister.1/bibliography/45647978/public/?sort=date&direction=descending

27 selected journal publications since 2010 include: 

1. Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus, Smith E, Janovick JA, Bannister TD, Shumate J, Scampavia L, Conn PM, Spicer TP., Journal of Biomolecular Screening 2016 Jun 8. pii: 1087057116653925. [Epub ahead of print], PMID: 27280550.

2. Synthesis and Cytoxicity of Sempervirine and Analogues. Pan, X.; Yang, C.; Cleveland, J.L, Bannister, T.D. Journal of Organic Chemistry 2016, 81(5), 2194-2200.

3. Tale of Two Protecting Groups—Boc vs SEM—for Directed Lithiation and C–C Bond Formation on a Pyrrolopyridazinone Core, Nair, R.N., Bannister, T.D.Organic Process Research and Development, 2016, 20 (7), 1370–1376.

4. Exploiting the co-reliance of tumours upon transport of amino acids and lactate: Gln and Tyr conjugates of MCT1 inhibitors. Nair, R. N.; Mishra, J. K.; Li, F.; Tortosa, M.; Yang, C.; Doherty, J. R.; Cameron, C.; Cleveland, J. L.; Roush, W. R.; Bannister, T. D. Medicinal Chemistry Communications 2016, 7(5), 900-905.

5. ML264 - a novel small-molecule compound that potently inhibits growth of colorectal cancer. de Sabando, A. R.; Wang, C.;  He, Y.; García-Barros, M.; Kim, J.; Shroyer, K. R.; Bannister, T. D.; Yang, V. W.; B. Bialkowska, A. B. Molecular Cancer Therapeutics, 2016, 15(1), 72-83. The article may be accessed at: http://mct.aacrjournals.org/content/early/2015/11/26/1535-7163.MCT-15-0600.abstract

6. Identification of Small Molecules that Disrupt Signaling between ABL and Its Positive Regulator RIN1. Ting, P. Y., Damoiseaux, R.; Titz, B.; Bradley, K. A.; Graeber, T. G.; Fernández-Vega, V.; Bannister, T.D.; Chase, P.; Nair, R.; Scampavia, L.; Hodder, P.; Spicer, T.P.; Colicelli, J. PLoS One 2015, 10(3): e0121833. doi:10.1371 /journal.pone.0121833

7. One-Pot Directed Alkylation/Deprotection Strategy for the Synthesis of Substituted Pyrrole[3,4-d]pyridazinones. Nair RN, Bannister TD. European Journal of Organic Chemistry 2015, 1764–1770.

8. Preparation of tetrasubstituted pyrimido[4,5-d]pyrimidine diones. Wang H, Wang C, Bannister TD. Tetrahedron Letters 2015, 56 (15), 1949–1952.

9. Identification of Potent Inhibitors of the Trypanosoma brucei Methionyl-tRNS Synthestase via High-Throughput Orthogonal Screening. Pedro-Rosa, L., Buckner, F.S., Ranade, R.M., Eberhardt, C., Madoux, F., Gillespie, J.R., Koh, C.Y., Brown, S., Lohse, J., Verlinde, C.L.M., Fan, E., Bannister, T., Scampavia,  L., Hol, W.M.G., Spicer, T., & Hodder, P. J. Journal of Biomolecular Screening 2015, 20(1), 122–130.

10. Synthesis and Structure-Activity Relationships of Pteridine Dione and Trione Monocarboxylate Transporter 1 Inhibitor, Wang H, Bannister, TD. Journal of Medicinal Chemistry 2014, 57 (17), 7317–7324.

11. Sequential Sonagashira and Larock Indole Synthesis Reactions in a General Strategy To Prepare Biologically Active β-Carboline-Containing Alkaloids. Pan X, Bannister TD. Organic Letters 2014, 16(23), 6124–6127.

12. Grubbs Cross-Metathesis Pathway for a Scalable Synthesis of gamma-keto alpha,beta- unsaturated Esters.  Nair R, Bannister, TD.  Journal of Organic Chemistry. 2014, 79 (3), 1467–1472.

13. Blocking Lactate Export by Inhibiting the Myc Target MCT1 Disables Glycolysis and Glutathione Synthesis. Doherty JR, Yang C, Scott KEN, Michael Cameron MD, Fallahi M, Li W, Hall MA, Amelio AL, Mishra JK, Li F, Tortosa M, Genau HM, Rounbehler RJ, Yungi L, Dang CV, K. Kumar KG, Butler AA, Bannister TD,  Hooper AT, Unsal-Kacmaz K, Roush WR and Cleveland JL. Cancer Research 2014, 74, 908-920.

14. Hydroxyquinoline-derived compounds and analoguing of selective MCL-1 inhibitors using a functional biomarker. David J. Richard, Ryan Lena, Noel Blake, William E. Pierceall, Nicole E. Carlson, Thomas Bannister, Christina Eberhart Keller, Marcel Koenig, Yuanjun He, Dmitriy Minond, Jitendra Mishra, Timothy Spicer, Michael Cameron, Peter Hodder, and Michael H. Cardone. Bioorganic and Medicinal Chemistry Letters, 2013, 21, 6642-6649.

15. Amygdala-Dependent Fear Is Regulated by Oprl1 in Mice and Humans with PTSD.  Andero R, Brothers SP, Jovanoviv T, Chen YT, Salah-Uddin H, Cameron M, Bannister TD, Almli L, Stevens JS, Bradley B, Bonder EB, Wahlestedt C, Ressler KJ. Science Translational Medicine, 2013,  5 (188), p. 188ra73, online in advance of print: http://stm.sciencemag.org/content/5/188/188ra73.

16. Amino acid derived quinazolines as Rock/PKA inhibitors. Chowdhury S, Chen YT, Fang X, Grant W, Pocas J, Cameron MD, Ruiz C, Lin L, Park H, Schröter T, Bannister TD, Lograsso PV, Feng Y. Bioorganic and Medicinal Chemistry Letters 2013, 23(6):1592-9.

17. ML264: An Antitumor Agent that Potently and Selectively Inhibits Krüppel-like Factor Five (KLF5) Expression: A Probe for Studying Colon Cancer Development and Progression. Agnieszka Bialkowska, Melissa Crisp, Franck Madoux, Tim Spicer, Ania Knapinska, Becky Mercer, Thomas D. Bannister, Yuanjun He, Sarwat Chowdhury, Michael Cameron, Vincent W. Yang, and Peter Hodder.  Probe Reports from the NIH Molecular Libraries Program [Internet], March 7, 2013, http://www.ncbi.nlm.nih.gov/books/NBK143546/

18. ML328: A Novel Dual Inhibitor of Bacterial AddAB and RecBCD Helicase-nuclease DNA Repair Enzymes. TD Bannister, R Nair, T Spicer, V Fernandez Vega, C Eberhart, BA Mercer, M Cameron, S Schurer, SK Amundsen, A Karabulut, LM Londoño, GR Smith, and P Hodder. Probe Reports from the NIH Molecular Libraries Program [Internet], April 5, 2013, http://www.ncbi.nlm.nih.gov/books/NBK148492/

19. ML311: A Small Molecule that Potently and Selectively Disrupts the Protein-Protein Interaction of Mcl-1 and Bim: A Probe for Studying Lymphoid Tumorigenesis. Thomas Bannister, Marcel Koenig, Yuanjun He, Jitendra Mishra, Tim Spicer, Dmitriy Minond, Adrian Saldanha, Becky A. Mercer, Michael Cameron, Ryan Lena, Nicole Carlson, David Richard, Michael Cardone, and Peter Hodder. Probe Reports from the NIH Molecular Libraries Program [Internet], March 14, 2013, http://www.ncbi.nlm.nih.gov/books/NBK143557/

20. ML345: A Small-Molecule Inhibitor of the Insulin-Degrading Enzyme (IDE). TD Bannister, H Wang, SO Abdul-Hay, A Masson, F Madoux, J Ferguson, BA Mercer, S Schurer, A Zuhl, BF Cravatt, MA Leissring, and P Hodder.  Probe Reports from the NIH Molecular Libraries Program [Internet], April 5, 2013, http://www.ncbi.nlm.nih.gov/books/NBK148499/

21. Small-Molecule Inhibitors of Bacterial AddAB and RecBCD Helicase-Nuclease DNA Repair Enzymes. Amundsen, S.K, Spicer, T., Karabulet, A.C., Londoño, L.M., Eberhardt, C., Vega, V.F., Bannister, T.D., Hodder, P., Smith, G.R. ACC Chemical Biology 2012, 7(5), 879-91.

22. Identification of Small-Molecule Inhibitors of the Colorectal Cancer Oncogene Kruppel-Like Factor 5 Expression by Ultrahigh-Throughput Screening. Bialkowska A, Crisp M, Bannister T, He Y, Chowdhury S, Schurer S, Chase P, Spicer T, Madoux F, Tian C, Hodder P, Zaharevitz D, Yang VW. Molecular Cancer Therapeutics, 2011, 10, 2043-2051.

23. Asymmetric synthesis of potent chroman-based Rho kinase (ROCK-II) inhibitors. Chen, Yen-Ting; Vojkovsky, Tomas; Fang, Xin-Gang; Pocas, Jennifer R.; Grant, Wayne; Handy, Amiee M. W.; Schroeter, Thomas; LoGrasso, Philip; Bannister, Thomas D.; Feng, Yangbo. Med Chem Comm (2011), 2(1), 73-75. 

24. Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I). Sarwat Chowdhury, E. Hampton Sessions, Jennifer R. Pocas, Wayne Grant, Thomas Schröter, Li Lin, Claudia Ruiz, Michael D. Cameron, Stephan Schürer, Philip LoGrasso, Thomas D. Bannister, Yangbo Feng. Bioorganic and Medicinal Chemistry Letters (2011), 7107-7012.

25. Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-II). E. Hampton Sessions, Sarwat Chowdhury, , Jennifer R. Pocas, Wayne Grant, Thomas Schröter, Li Lin, Claudia Ruiz, Michael D. Cameron, Stephan Schürer, Philip LoGrasso, Thomas D. Bannister, Yangbo Feng. Bioorganic and Medicinal Chemistry Letters 2011, 7113-7118.

26. Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors. Fang Xingang; Chen Yen Ting; Sessions E Hampton; Chowdhury Sarwat; Vojkovsky Tomas; Yin Yan; Pocas Jennifer R; Grant Wayne; Schroter Thomas; Lin Li, Bannister, Thomas D.; et al.Bioorganic and Medicinal Chemistry Letters 2011, 21(6), 1844-8.

27. The development of benzimidazoles as selective rho kinase inhibitors. Sessions, E. Hampton; Smolinski, Michael; Wang, Bo; Frackowiak, Bozena; Chowdhury, Sarwat; Yin, Yan; Chen, Yen Ting; Ruiz, Claudia; Lin, Li; Pocas, Jennifer, Bannister, Thomas D.; et al.  Bioorganic and Medicinal Chemistry Letters 2010, 20(6), 1939-1943.

Links

Bannister Lab Receives Funding to Develop New PTSD Treatments

Scientists Win $2 Million to Identify Potential New Treatments for Schizophrenia and Depression

Scripps Florida Scientists Awarded $3 Million to Develop New, More Effective Pain Treatments

Scripps Florida Scientist Awarded $700,000 to Develop New Treatments for Cocaine Addiction

A Lab with a View: Tom Bannister Looks for Potential New Drugs