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Bohn, Laura
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Bohn, Laura

Faculty Member
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Positions

  • 2017 - Professor (endowed, Dembling Endowment Fund for Drug Discovery and Human Health Research), Molecular Medicine , Scripps Research
  • 2016 - Affiliate Research Professor, Florida Atlantic University Brain Institute , Florida Atlantic University
  • 2014 - Professor (tenured, Joint Appointment), Neuroscience , Scripps Research
  • 2009 - Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2014 - 2017 Professor (tenured), Molecular Therapeutics , Scripps Research
  • 2009 - 2014 Associate Professor (tenured), Molecular Therapeutics , Scripps Research
  • 2009 - 2014 Associate Professor (tenured, Joint Appointment), Neuroscience , Scripps Research
  • 2007 - 2009 Associate Professor (tenured), College of Medicine, Departments of Pharmacology and Psychiatry, The Ohio State University
  • 2003 - 2007 Assistant Professor, College of Medicine, Departments of Pharmacology and Psychiatry, The Ohio State University
  • 2002 - 2003 Assistant Research Professor, Duke University Medical Center Department of Cell Biology, Duke University
  • 1999 - 2002 Postdoctoral Scholar, Medical Center, Department of Cell Biology, Howard Hughes Medical Institute, Duke University

Research in the Bohn laboratory is focused on understanding how G protein-coupled receptors function in an endogenous setting to control physiologically relevant processes. We are most interested in receptors that mediate neurological functions, particularly those of the opioid, serotonin and cannabinoid families. Ultimately, our goal is to refine therapeutics- to enhance the benefits and eliminate the side effects. In this manner, we hope to inspire new approaches in treating pain, addiction and mood disorders.

The Bohn laboratory is most widely known for our work in opioid receptors. Early work while in the laboratory of Marc Caron and in collaboration with Robert Lefkowitz at Duke University indicated that barrestin2 plays a critical role in determining the physiological role of the mu opioid receptor (MOR) in vivo. Our laboratory has shown that barrestin2 plays different roles in regulating the MOR depending upon the physiological function assessed. This is very important as activation of the MOR results in multiple physiological processes ranging from the highly desirable suppression of pain perception to the deadly effects of respiratory failure. By determining which barrestin2-mediated signaling pathways are associated with these different physiological outcomes, we aim to elucidate a means to develop potent opioid analgesics that circumvent the adverse side effects. The bulk of our work to date suggests that if we preserve MOR coupling to G proteins, but eliminate the interactions between the receptor and the scaffolding protein, barrestin2, then we may be able to separate analgesic potency from constipation, respiratory suppression, tolerance and physical dependence.

Our lab is now focused on developing compounds that will allow us to test these hypotheses and to identify candidates for drug development. Our agonists are designed, in collaboration with Dr. Tom Bannister of TSRI, to activate MOR in a manner that preserves or improves G protein signaling while eliminating the recruitment of barrestins. In addition to generating potential therapeutic leads, we are very interested in using these tools to elucidate MOR function in vivo. As we refine the pathways underlying different physiological responses, we will then know the signaling mechanisms to preserve and the ones to avoid.

We are also taking a similar approach with the kappa opioid receptors (KOR). The KOR in the midbrain acts to regulate dopamine and serotonin levels and thereby serves as an attractive target for modulating mood and reward thresholds. KOR ligands that display bias towards or against recruiting barrestins are of interest as barrestin2 has been implicated in facilitating aversive KOR-mediated behaviors. In our work with Dr. Jeff Aubé of Kansas University, we have been developing and evaluating KOR biased agonists to determine which physiologies are preserved or disrupted in mouse models. Since the KOR is involved in diverse physiological functions, compounds generated in this project may serve as interesting candidates for the treatment of depressive disorders and addiction. Moreover, KOR agonism produces antinociception and blocks itch and may also represent potential therapeutic avenues.

Recently, we have begun evaluating ligands for biased agonism among cannabinoid receptor (CB1 and CB2) agonists in collaboration with Dr. Alex Makriyannis at Northeastern University. Given the emerging implications for using cannabinoids as therapeutics for a wide-range of disorders, there are many opportunities for new drug development. This collaboration has also involved working with Dr. Ray Stevens (USC) and Dr. James Liu (Shanghai Tech) to solve the first crystal structures of antagonist and agonist bound CB1 receptors. Additional efforts in the laboratory focus on evaluating how antipsychotic drugs and mood altering neurotransmitters such as serotonin act at serotonin receptors.

Since the receptors described above are involved in modulating mood, motivation, and sensory perception, it stands to reason that our laboratory is most interested in developing means to treat pain, whether due to injury, disease or mental state, in a manner that adequately manages the pain, without causing deabilitating side effects

Research Areas research areas

  • Addiction (UMLS)
  • Mental Illness (UMLS)

Contact

  • lbohn@scripps.edu
  • (561) 228-2227

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  • Laura Bohn, Ph.D.
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Publications

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    • Cornelissen, J. C., Blough, B. E., Bohn, L. M., Negus, S. S., Banks, M. L. Some effects of putative G-protein biased mu-opioid receptor agonists in male rhesus monkeys Behavioural Pharmacology  2021 32:453-458  DOI:10.1097/fbp.0000000000000634  PMID:33883450  PMCID:PMC8266741
    • Stahl, E. L., Bohn, L. M. Decaf or regular? Energizing the caffeine receptor Cell  2021 184:1659-1660  DOI:10.1016/j.cell.2021.03.016  PMID:33798438
    • Jiang, S., Iliopoulos-Tsoutsouvas, C., Tong, F., Brust, C. A., Keenan, C. M., Raghav, J. G., Hua, T., Wu, S. M., Ho, J. H., Wu, Y. R., Grim, T. W., Zvonok, N., et al. Novel Functionalized Cannabinoid Receptor Probes: Development of Exceptionally Potent Agonists Journal of Medicinal Chemistry  2021 64:3870-3884  DOI:10.1021/acs.jmedchem.0c02053  PMID:33761251
    • Wang, X. Y., Liu, D. S., Shen, L., Li, F. H., Li, Y. Z., Yang, L. Y., Xu, T. D., Tao, H. C., Yao, D. Q., Wu, L. J., Hirata, K., Bohn, L. M., et al. A Genetically Encoded F-19 NMR Probe Reveals the Allosteric Modulation Mechanism of Cannabinoid Receptor 1 Journal of the American Chemical Society  2021 143:16320-16325  DOI:10.1021/jacs.1c06847  PMID:34596399
    • Stahl, E. L., Schmid, C. L., Acevedo-Canabal, A., Read, C., Grim, T. W., Kennedy, N. M., Bannister, T. D., Bohn, L. M. G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists Proceedings of the National Academy of Sciences of the United States of America  2021 118  DOI:10.1073/pnas.2102178118  PMID:34819362  PMCID:PMC8640941
    • Frankowski, K. J., Brust, T., Lovell, K. M., Yoo, E., Bohn, L. M., Aube, J. Structure-activity relationship investigation of triazole-based kappa opioid receptor agonists Medicinal Chemistry Research  2021  DOI:10.1007/s00044-021-02746-1
    • Pantouli, F., Grim, T. W., Schmid, C. L., Acevedo-Canabal, A., Kennedy, N. M., Cameron, M. D., Bannister, T. D., Bohn, L. M. Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain Neuropharmacology  2020 185  DOI:10.1016/j.neuropharm.2020.108439  PMID:33345829  PMCID:PMC7887086
    • Hua, T., Li, X., Wu, L., Iliopoulos-Tsoutsouvas, C., Wang, Y., Wu, M., Shen, L., Johnston, C. A., Nikas, S. P., Song, F., Song, X., Yuan, S., et al. Activation and signaling mechanism revealed by cannabinoid receptor-G(i) complex structures Cell  2020 180:655-665  DOI:10.1016/j.cell.2020.01.008  PMID:32004463
    • Grim, T. W., Schmid, C. L., Stahl, E. L., Pantouli, F., Ho, J. H., Acevedo-Canabal, A., Kennedy, N. M., Cameron, M. D., Bannister, T. D., Bohn, L. M. A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal Neuropsychopharmacology  2020 45:416-425  DOI:10.1038/s41386-019-0491-8  PMID:31443104
    • Grim, T. W., Acevedo-Canabal, A., Bohn, L. M. Toward directing opioid receptor signaling to refine opioid therapeutics Biological Psychiatry  2020 87:15-21  DOI:10.1016/j.biopsych.2019.10.020  PMID:31806082
    • Laprairie, R. B., Vemuri, K., Stahl, E. L., Korde, A., Ho, J. H., Grim, T. W., Hua, T., Wu, Y., Stevens, R. C., Liu, Z. J., Makriyannis, A., Bohn, L. M. Probing the CB1 Cannabinoid Receptor Binding Pocket with AM6538, a High-Affinity Irreversible Antagonist Molecular Pharmacology  2019 96:619-628  DOI:10.1124/mol.119.116483
    • Li, X., Hua, T., Vemuri, K., Ho, J. H., Wu, Y., Wu, L., Popov, P., Benchama, O., Zvonok, N., Locke, K., Qu, L., Han, G. W., et al. Crystal structure of the human cannabinoid receptor CB2 Cell  2019 176:459-467  DOI:10.1016/j.cell.2018.12.011  PMID:30639103
    • Kennedy, N. M., Schmid, C. L., Ross, N. C., Lovell, K. M., Yue, Z., Chen, Y. T., Cameron, M. D., Bohn, L. M., Bannister, T. D. Optimization of a series of mu opioid receptor (MOR) agonists with high G protein signaling bias Journal of Medicinal Chemistry  2018 61:8895-8907  DOI:10.1021/acs.jmedchem.8b01136  PMID:30199635
    • Tosh, D. K., Ciancetta, A., Mannes, P., Warnick, E., Janowsky, A., Eshleman, A. J., Gizewski, E., Brust, T. F., Bohn, L. M., Auchampach, J. A., Gao, Z. G., Jacobson, K. A. Repurposing of a nucleoside scaffold from adenosine receptor agonists to opioid receptor Antagonists ACS Omega  2018 3:12658-12678  DOI:10.1021/acsomega.8b01237  PMID:30411015  PMCID:PMC6210068
    • Grim, T. W., Park, S. J., Schmid, C. L., Laprairie, R. B., Cameron, M., Bohn, L. M. The effect of quinine in two bottle choice procedures in C57BL6 mice: Opioid preference, somatic withdrawal, and pharmacokinetic outcomes Drug and Alcohol Dependence  2018 191:195-202  DOI:10.1016/j.drugalcdep.2018.05.034  PMID:30138791
    • Hirasawa, S., Cho, M., Brust, T. F., Roach, J. J., Bohn, L. M., Shenvi, R. A. O6C-20-nor-salvinorin A is a stable and potent KOR agonist Bioorganic & Medicinal Chemistry Letters  2018 28:2770-2772  DOI:10.1016/j.bmcl.2018.01.055  PMID:29426768  PMCID:PMC6067998
    • Donthamsetti, P., Gallo, E. F., Buck, D. C., Stahl, E. L., Zhu, Y., Lane, J. R., Bohn, L. M., Neve, K. A., Kellendonk, C., Javitch, J. A. Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation Molecular Psychiatry  2018 25:2086-2100  DOI:10.1038/s41380-018-0212-4  PMID:30120413  PMCID:PMC6378141
    • Ho, J. H., Stahl, E. L., Schmid, C. L., Scarry, S. M., Aube, J., Bohn, L. M. G protein signaling-biased agonism at the κ-opioid receptor is maintained in striatal neurons Science Signaling  2018 11  DOI:10.1126/scisignal.aar4309  PMID:30087177
    • Roach, J. J., Sasano, Y., Schmid, C. L., Zaidi, S., Katritch, V., Stevens, R. C., Bohn, L. M., Shenvi, R. A. Dynamic strategic bond analysis yields a ten-step synthesis of 20-nor-salvinorin A, a potent κ-OR agonist ACS Central Science  2017 3:1329-1336  DOI:10.1021/acscentsci.7b00488  PMID:29296674  PMCID:PMC5746855
    • Schmid, C. L., Kennedy, N. M., Ross, N. C., Lovell, K. M., Yue, Z., Morgenweck, J., Cameron, M. D., Bannister, T. D., Bohn, L. M. Bias factor and therapeutic window correlate to predict safer opioid analgesics Cell  2017 171:1165-1175  DOI:10.1016/j.cell.2017.10.035  PMID:29149605
    • Hua, T., Vemuri, K., Nikas, S. P., Laprairie, R. B., Wu, Y., Qu, L., Pu, M., Korde, A., Jiang, S., Ho, J. H., Han, G. W., Ding, K., et al. Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature  2017 547:468-471  DOI:10.1038/nature23272  PMID:28678776
    • Bohn, L. M., Aube, J. Seeking (and finding) biased ligands of the kappa opioid receptor ACS Medicinal Chemistry Letters  2017 8:694-700  DOI:10.1021/acsmedchemlett.7b00224  PMID:28740600  PMCID:PMC5512133
    • Mason, J. W., Schmid, C. L., Bohn, L. M., Roush, W. R. Stolonidiol: Synthesis, target identification, and mechanism for choline acetyltransferase activation Journal of the American Chemical Society  2017 139:5865-5869  DOI:10.1021/jacs.7b01083  PMID:28414442
    • Laprairie, R. B., Stahl, E. L., Bohn, L. M. Approaches to assess biased signaling at the CB1R receptor Methods in Enzymology  2017 593:259-279  DOI:10.1016/bs.mie.2017.06.031  PMID:28750807
    • Brust, T. F., Morgenweck, J., Kim, S. A., Rose, J. H., Locke, J. L., Schmid, C. L., Zhou, L., Stahl, E. L., Cameron, M. D., Scarry, S. M., Aube, J., Jone, S. R., et al. Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria Science Signaling  2016 9  DOI:10.1126/scisignal.aai8441  PMID:27899527
    • Shahani, N., Swarnkar, S., Giovinazzo, V., Morgenweck, J., Bohn, L. M., Scharager-Tapia, C., Pascal, B., Martinez-Acedo, P., Khare, K., Subramaniam, S. RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network ("Rhesactome") in the striatum Science Signaling  2016 9  DOI:10.1126/scisignal.aaf6670  PMID:27902448  PMCID:PMC5142824
    • Scarry, S. M., Lovell, K. M., Frankowski, K. J., Bohn, L. M., Aube, J. Synthesis of kappa opioid antagonists based on pyrrolo[1,2-α]quinoxalinones using an N-arylation/condensation/oxidation reaction sequence Journal of Organic Chemistry  2016 81:10538-10550  DOI:10.1021/acs.joc.6b01350  PMID:27399050
    • Hua, T., Vemuri, K., Pu, M., Qu, L., Han, G. W., Wu, Y., Zhao, S., Shui, W., Li, S., Korde, A., Laprairie, R. B., Stahl, E. L., et al. Crystal structure of the human cannabinoid receptor CB1 Cell  2016 167:750-762  DOI:10.1016/j.cell.2016.10.004  PMID:27768894
    • Rodrigues, P. R., Kaul, T. K., Ho, J. H., Lucanic, M., Burkewitz, K., Mair, W. B., Held, J. M., Bohn, L. M., Gill, M. S. Synthetic ligands of cannabinoid receptors affect dauer formation in the nematode Caenorhabditis elegans G3-Genes Genomes Genetics  2016 6:1695-1705  DOI:10.1534/g3.116.026997  PMID:27172180  PMCID:PMC4889665
    • You, I. J., Wright, S. R., Garcia-Garcia, A. L., Tapper, A. R., Gardner, P. D., Koob, G. F., Leonardo, E. D., Bohn, L. M., Wee, S. 5-HT1A autoreceptors in the dorsal raphe nucleus convey vulnerability to compulsive cocaine seeking Neuropsychopharmacology  2016 41:1210-1222  DOI:10.1038/npp.2015.268  PMID:26324408  PMCID:PMC4793105
    • Ho, J. H., Lovell, K., Zhou, L., Frankowski, K., Aube, J., Bohn, L. M. Characterization of novel biased KOR agonist-mediated cell signaling FASEB Journal  2016 30
    • Rankovic, Z., Brust, T. F., Bohn, L. M. Biased agonism: An emerging paradigm in GPCR drug discovery Bioorganic & Medicinal Chemistry Letters  2016 26:241-250  DOI:10.1016/j.bmcl.2015.12.024  PMID:26707396
    • Green, J. A., Schmid, C. L., Bley, E., Monsma, P. C., Brown, A., Bohn, L. M., Mykytyn, K. Recruitment of β-arrestin into neuronal cilia modulates somatostatin receptor subtype 3 ciliary localization Molecular and Cellular Biology  2016 36:223-235  DOI:10.1128/mcb.00765-15  PMID:26503786
    • Zhou, L., Stahl, E. L., Lovell, K. M., Frankowski, K. J., Prisinzano, T. E., Aube, J., Bohn, L. M. Characterization of kappa opioid receptor mediated, dynorphin-stimulated [(35)S]GTPγS binding in mouse striatum for the evaluation of selective KOR ligands in an endogenous setting Neuropharmacology  2015 99:131-141  DOI:10.1016/j.neuropharm.2015.07.001  PMID:26160155  PMCID:PMC4655192
    • Morgenweck, J., Frankowski, K. J., Prisinzano, T. E., Aube, J., Bohn, L. M. Investigation of the role of βarrestin2 in kappa opioid receptor modulation in a mouse model of pruritus Neuropharmacology  2015 99:600-609  DOI:10.1016/j.neuropharm.2015.08.027  PMID:26318102  PMCID:PMC4739521
    • Bohn, L. M., Lohse, M. J., Nitabach, M. N., Taghert, P. H., Smit, M. J. Exploring the biology of G protein-coupled receptors from in vitro to in vivo Molecular Pharmacology  2015 88:534-535  DOI:10.1124/mol.115.100750  PMID:26162863
    • Luttrell, L. M., Maudsley, S., Bohn, L. M. Fulfilling the promise of "biased" G protein-coupled receptor agonism Molecular Pharmacology  2015 88:579-588  DOI:10.1124/mol.115.099630  PMID:26134495  PMCID:PMC4551052
    • Janero, D. R., Yaddanapudi, S., Zvonok, N., Subramanian, K. V., Shukla, V. G., Stahl, E., Zhou, L., Hurst, D., Wager-Miler, J., Bohn, L. M., Reggio, P. H., Mackie, K., et al. Molecular-interaction and signaling profiles of AM3677, a novel covalent agonist selective for the cannabinoid 1 receptor ACS Chemical Neuroscience  2015 6:1400-1410  DOI:10.1021/acschemneuro.5b00090  PMID:25978068  PMCID:PMC4804703
    • Lovell, K. M., Frankowski, K. J., Stahl, E. L., Slauson, S. R., Yoo, E., Prisinzano, T. E., Aubé, J., Bohn, L. M. Structure-activity relationship studies of functionally selective kappa opioid receptor agonists that modulate ERK 1/2 phosphorylation while preserving G protein over βarrestin2 signaling bias ACS Chemical Neuroscience  2015 6:1411-1419  DOI:10.1021/acschemneuro.5b00092  PMID:25891774  PMCID:PMC4830356
    • Frankowski, K. J., Slauson, S. R., Lovell, K. M., Phillips, A. M., Streicher, J. M., Zhou, L., Whipple, D. A., Schoenen, F. J., Prisinzano, T. E., Bohn, L. M., Aube, J. Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif Bioorganic & Medicinal Chemistry  2015 23:3948-3956  DOI:10.1016/j.bmc.2014.12.033  PMID:25593096  PMCID:PMC4468036
    • Stahl, E. L., Zhou, L., Ehlert, F. J., Bohn, L. M. A novel method for analyzing extremely biased agonism at G protein-coupled receptors Molecular Pharmacology  2015 87:866-877  DOI:10.1124/mol.114.096503  PMID:25680753  PMCID:PMC4407734
    • Bohn, L. M., Zhou, L., Ho, J. H. Approaches to assess functional selectivity in GPCRs: evaluating G protein signaling in an endogenous environment Methods in Molecular Biology  2015 1335:177-189  DOI:10.1007/978-1-4939-2914-6_12  PMID:26260601  PMCID:PMC4804702
    • Zhou, L., Bohn, L. M. Functional selectivity of GPCR signaling in animals Current Opinion in Cell Biology  2014 27:102-108  DOI:10.1016/j.ceb.2013.11.010  PMID:24680435  PMCID:PMC4349326
    • Raehal, K. M., Bohn, L. M. beta-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia Handbook of Experimental Pharmacology  2014 219:427-443  DOI:10.1007/978-3-642-41199-1_22  PMID:24292843  PMCID:PMC4804701
    • Zhou, L., Lovell, K. M., Frankowski, K. J., Slauson, S. R., Phillips, A. M., Streicher, J. M., Stahl, E., Schmid, C. L., Hodder, P., Madoux, F., Cameron, M. D., Prisinzano, T. E., et al. Development of functionally selective, small molecule agonists at kappa opioid receptors Journal of Biological Chemistry  2013 288:36703-36716  DOI:10.1074/jbc.M113.504381  PMID:24187130  PMCID:PMC3868780
    • Schmid, C. L., Streicher, J. M., Groer, C. E., Munro, T. A., Zhou, L., Bohn, L. M. Functional selectivity of 6'-guanidinonaltrindole (6'-GNTI) at kappa-opioid receptors in striatal neurons Journal of Biological Chemistry  2013 288:22387-22398  DOI:10.1074/jbc.M113.476234  PMID:23775075  PMCID:PMC3829329
    • Zhou, H., Chisari, M., Raehal, K. M., Kaltenbronn, K. M., Bohn, L. M., Mennerick, S. J., Blumer, K. J. Girk channel modulation by assembly with allosterically regulated RGS proteins Proceedings of the National Academy of Sciences of the United States of America  2012 109:19977-19982  DOI:10.1073/pnas.1214337109  PMID:23169654  PMCID:PMC3523866
    • Nguyen, P. T., Schmid, C. L., Raehal, K. M., Selley, D. E., Bohn, L. M., Sim-Selley, L. J. Beta-arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner Biological Psychiatry  2012 71:714-724  DOI:10.1016/j.biopsych.2011.11.027  PMID:22264443  PMCID:PMC3319102
    • Lamb, K., Tidgewell, K., Simpson, D. S., Bohn, L. M., Prisinzano, T. E. Antinociceptive effects of herkinorin, a MOP receptor agonist derived from salvinorin A in the formalin test in rats: New concepts in mu opioid receptor pharmacology: From a symposium on new concepts in mu-opioid pharmacology Drug and Alcohol Dependence  2012 121:181-188  DOI:10.1016/j.drugalcdep.2011.10.026  PMID:22119134  PMCID:PMC3288203
    • Frankowski, K. J., Hedrick, M. P., Gosalia, P., Li, K. L., Shi, S. H., Whipple, D., Ghosh, P., Prisinzano, T. E., Schoenen, F. J., Su, Y., Vasile, S., Sergienko, E., et al. Discovery of small molecule kappa opioid receptor agonist and antagonist chemotypes through a HTS and Hit refinement strategy ACS Chemical Neuroscience  2012 3:221-236  DOI:10.1021/cn200128x  PMID:22737280  PMCID:PMC3378255
    • Beguin, C., Potuzak, J., Xu, W., Liu-Chen, L. Y., Streicher, J. M., Groer, C. E., Bohn, L. M., Carlezon, W. A., Cohen, B. M. Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues Bioorganic & Medicinal Chemistry Letters  2012 22:1023-1026  DOI:10.1016/j.bmcl.2011.11.128  PMID:22204910  PMCID:PMC3926198
    • Raehal, K. M., Schmid, C. L., Groer, C. E., Bohn, L. M. Functional selectivity at the mu-opioid receptor: Implications for understanding opioid analgesia and tolerance Pharmacological Reviews  2011 63:1001-1019  DOI:10.1124/pr.111.004598  PMID:21873412  PMCID:PMC3186080
    • Groer, C. E., Schmid, C. L., Jaeger, A. M., Bohn, L. M. Agonist-directed interactions with specific beta-arrestins determine mu-opioid receptor trafficking, ubiquitination, and dephosphorylation Journal of Biological Chemistry  2011 286:31731-31741  DOI:10.1074/jbc.M111.248310  PMID:21757712  PMCID:PMC3173119
    • Tarselli, M. A., Raehal, K. M., Brasher, A. K., Streicher, J. M., Groer, C. E., Cameron, M. D., Bohn, L. M., Micalizio, G. C. Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain Nature Chemistry  2011 3:449-453  DOI:10.1038/nchem.1050  PMID:21602859
    • Sun, X. H., Wang, X. Y., Wang, G. D., Xia, Y., Liu, S. M., Qu, M. H., Needleman, B. J., Mikami, D. J., Melvin, W. S., Bohn, L. M., Ueno, R., Wood, J. D. Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine Digestive Diseases and Sciences  2011 56:330-338  DOI:10.1007/s10620-010-1515-8  PMID:21181441  PMCID:PMC4757489
    • Bohn, L. M., McDonald, P. H. Detecting the role of arrestins in G protein-coupled receptor regulation Neuromethods  2011 60:347-358  DOI:10.1007/978-1-61779-179-6_17
    • Raehal, K. M., Bohn, L. M. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics Neuropharmacology  2011 60:58-65  DOI:10.1016/j.neuropharm.2010.08.003  PMID:20713067  PMCID:PMC2981657
    • Bohn, L. M., Schmid, C. L. Serotonin receptor signaling and regulation via beta-arrestins Critical Reviews in Biochemistry and Molecular Biology  2010 45:555-566  DOI:10.3109/10409238.2010.516741  PMID:20925600  PMCID:PMC4776633
    • Schmid, C. L., Bohn, L. M. Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a beta-arrestin2/Src/Akt signaling complex in vivo Journal of Neuroscience  2010 30:13513-13524  DOI:10.1523/jneurosci.1665-10.2010  PMID:20926677  PMCID:PMC3001293
    • Fei, G. J., Raehal, K., Liu, S. M., Qu, M. H., Sun, X. H., Wang, G. D., Wang, X. Y., Xia, Y., Schmid, C. L., Bohn, L. M., Wood, J. D. Lubiprostone reverses the inhibitory action of morphine on intestinal secretion in guinea pig and mouse Journal of Pharmacology and Experimental Therapeutics  2010 334:333-340  DOI:10.1124/jpet.110.166116  PMID:20406855  PMCID:PMC2912047
    • Bohn, L. M., McDonald, P. H. Seeking ligand bias: assessing GPCR coupling to beta-arrestins for drug discovery Drug Discovery Today. Technologies  2010 7:e37-e42  DOI:10.1016/j.ddtec.2010.06.005  PMID:21218149  PMCID:PMC3014586
    • Raehal, K. M., Schmid, C. L., Medvedev, I. O., Gainetdinov, R. R., Premont, R. T., Bohn, L. M. Morphine-induced physiological and behavioral responses in mice lacking g protein-coupled receptor kinase 6 Drug and Alcohol Dependence  2009 104:187-196  DOI:10.1016/j.drugalcdep.2009.04.011  PMID:19497686  PMCID:PMC2771341
    • Zhang, L., Nothacker, H. P., Wang, Z. W., Bohn, L. M., Civelli, O. Pharmacological characterization of a selective agonist for bombesin receptor subtype-3 Biochemical and Biophysical Research Communications  2009 387:283-288  DOI:10.1016/j.bbrc.2009.07.006  PMID:19580790  PMCID:PMC2747518
    • Fei, G. J., Wang, Y. Z., Liu, S. M., Hu, H. Z., Wang, G. D., Qu, M. H., Wang, X. Y., Xia, Y., Sun, X. H., Bohn, L. M., Cooke, H. J., Wood, J. D. Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon American Journal of Physiology-Gastrointestinal and Liver Physiology  2009 296:G823-G832  DOI:10.1152/ajpgi.90447.2008  PMID:19179625  PMCID:PMC2670663
    • Schmid, C. L., Bohn, L. M. Physiological and pharmacological implications of beta-arrestin regulation Pharmacology & Therapeutics  2009 121:285-293  DOI:10.1016/j.pharmthera.2008.11.005  PMID:19100766  PMCID:PMC2656564
    • McLennan, G. P., Kiss, A., Miyatake, M., Belcheva, M. M., Chambers, K. T., Pozek, J. J., Mohabbat, Y., Moyer, R. A., Bohn, L. M., Coscia, C. J. Kappa opioids promote the proliferation of astrocytes via Gbetagamma and beta-arrestin 2-dependent MAPK-mediated pathways Journal of Neurochemistry  2008 107:1753-1765  DOI:10.1111/j.1471-4159.2008.05745.x  PMID:19014370  PMCID:PMC2606093
    • Tidgewell, K., Groer, C. E., Harding, W. W., Lozama, A., Schmidt, M., Marquam, A., Hiemstra, J., Partilla, J. S., Dersch, C. M., Rothman, R. B., Bohn, L. M., Prisinzano, T. E. Herkinorin analogues with differential beta-arrestin-2 interactions Journal of Medicinal Chemistry  2008 51:2421-2431  DOI:10.1021/jm701162g  PMID:18380425  PMCID:PMC2494883
    • Gupta, A., Rozenfeld, R., Gomes, I., Raehal, K. M., Decaillot, F. M., Bohn, L. M., Devi, L. A. Post-activation-mediated changes in opioid receptors detected by N-terminal antibodies Journal of Biological Chemistry  2008 283:10735-10744  DOI:10.1074/jbc.M709454200  PMID:18256033  PMCID:PMC2447646
    • Schmid, C. L., Raehal, K. M., Bohn, L. M. Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo Proceedings of the National Academy of Sciences of the United States of America  2008 105:1079-1084  DOI:10.1073/pnas.0708862105  PMID:18195357  PMCID:PMC2242710
    • Xu, H., Partilla, J. S., Wang, X. Y., Rutherford, J. M., Tidgewell, K., Prisinzano, T. E., Bohn, L. M., Rothman, R. B. A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence Synapse  2007 61:166-175  DOI:10.1002/syn.20356  PMID:17152090
    • Groer, C. E., Tidgewell, K., Moyer, R. A., Harding, W. W., Rothman, R. B., Prisinzano, T. E., Bohn, L. M. An opioid agonist that does not induce mu-opioid receptor - arrestin interactions or receptor internalization Molecular Pharmacology  2007 71:549-557  DOI:10.1124/mol.106.028258  PMID:17090705  PMCID:PMC3926195
    • Bohn, L. M., Raehal, K. M. Opioid receptor signaling: relevance for gastrointestinal therapy Current Opinion in Pharmacology  2006 6:559-563  DOI:10.1016/j.coph.2006.06.007  PMID:16935560
    • Raehal, K. M., Walker, J. K. L., Bohn, L. M. Morphine side effects in beta-arrestin 2 knockout mice Journal of Pharmacology and Experimental Therapeutics  2005 314:1195-1201  DOI:10.1124/jpet.105.087254  PMID:15917400
    • Medvedev, I. O., Gainetdinov, R. R., Sotnikova, T. D., Bohn, L. M., Caron, M. G., Dykstra, L. A. Characterization of conditioned place preference to cocaine in congenic dopamine transporter knockout female mice Psychopharmacology  2005 180:408-413  DOI:10.1007/s00213-005-2173-y  PMID:15719221
    • Wang, D. X., Sun, X. C., Bohn, L. M., Sadee, W. Opioid receptor homo- and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer Molecular Pharmacology  2005 67:2173-2184  DOI:10.1124/mol.104.010272.  PMID:15778451
    • Raehal, K. M., Bohn, L. M. Mu opioid receptor regulation and opiate responsiveness AAPS Journal  2005 7:E587-E591  DOI:10.1208/aapsj070360  PMID:16353937  PMCID:PMC2751262
    • Bohn, L. M., Dykstra, L. A., Lefkowitz, R. J., Caron, M. G., Barak, L. S. Relative opioid efficacy is determined by the complements of the G protein-coupled receptor desensitization machinery Molecular Pharmacology  2004 66:106-112  DOI:10.1124/mol.66.1.106  PMID:15213301
    • Johnson, E. C., Bohn, L. M., Taghert, P. H. Drosophila CG8422 encodes a functional diuretic hormone receptor Journal of Experimental Biology  2004 207:743-748  DOI:10.1242/jeb.00818  PMID:14747406
    • Gainetdinov, R. R., Premont, R. T., Bohn, L. M., Lefkowitz, R. J., Caron, M. G. Desensitization of G protein-coupled receptors and neuronal functions Annual Review of Neuroscience  2004 27:107-144  DOI:10.1146/annurev.neuro.27.070203.144206  PMID:15217328
    • Bohn, L. M., Gainetdinov, R. R., Caron, M. G. G protein-coupled receptor kinase/beta-arrestin systems and drugs of abuse - psychostimulant and opiate studies in knockout mice Neuromolecular Medicine  2004 5:41-50  DOI:10.1385/nmm:5:1:041  PMID:15001811
    • Johnson, E. C., Bohn, L. M., Barak, L. S., Birse, R. T., Nassel, D. R., Caron, M. G., Taghert, P. H. Identification of drosophila neuropeptide receptors by G protein-coupled receptors-beta-arrestin2 interactions Journal of Biological Chemistry  2003 278:52172-52178  DOI:10.1074/jbc.M306756200  PMID:14555656
    • Bohn, L. M., Gainetdinov, R. R., Sotnikova, T. D., Medvedev, I. O., Lefkowitz, R. J., Dykstra, L. A., Caron, M. G. Enhanced rewarding properties of morphine, but not cocaine, in beta arrestin-2 knock-out mice Journal of Neuroscience  2003 23:10265-10273  PMID:14614085
    • Cyr, M., Beaulieu, J. M., Laakso, A., Sotnikova, T. D., Yao, W. D., Bohn, L. M., Gainetdinov, R. R., Caron, M. G. Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons Proceedings of the National Academy of Sciences of the United States of America  2003 100:11035-11040  DOI:10.1073/pnas.1831768100  PMID:12958210  PMCID:PMC196922
    • Gainetdinov, R. R., Bohn, L. M., Sotnikova, T. D., Cyr, M., Laakso, A., Macrae, A. D., Torres, G. E., Kim, K. M., Lefkowitz, R. J., Caron, M. G., Premont, R. T. Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice Neuron  2003 38:291-303  DOI:10.1016/s0896-6273(03)00192-2  PMID:12718862
    • Bohn, L. M., Lefkowitz, R. J., Caron, M. G. Differential mechanisms of morphine antinociceptive tolerance revealed in beta arrestin-2 knock-out mice Journal of Neuroscience  2002 22:10494-10500  PMID:12451149
    • Wilbanks, A. M., Laporte, S. A., Bohn, L. M., Barak, L. S., Caron, M. G. Apparent loss-of-function mutant GPCRs revealed as constitutively desensitized receptors Biochemistry  2002 41:11981-11989  DOI:10.1021/bi020275m  PMID:12356298
    • Gainetdinov, R. R., Mohn, A. R., Bohn, L. M., Caron, M. G. Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter Proceedings of the National Academy of Sciences of the United States of America  2001 98:11047-11054  DOI:10.1073/pnas.191353298  PMID:11572967  PMCID:PMC58681
    • Bohn, L. M., Xu, F., Gainetdinov, R. R., Caron, M. G. Potentiated opioid analgesia in norepinephrine transporter knock-out mice Journal of Neuroscience  2000 20:9040-9045  PMID:11124980
    • Bohn, L. M., Gainetdinov, R. R., Lin, F. T., Lefkowitz, R. J., Caron, M. G. Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence Nature  2000 408:720-723  PMID:11130073
    • Bohn, L. M., Belcheva, M. M., Coscia, C. J. Mitogenic signaling via endogenous kappa-opioid receptors in C6 glioma cells: Evidence for the involvement of protein kinase C and the mitogen-activated protein kinase signaling cascade Journal of Neurochemistry  2000 74:564-573  DOI:10.1046/j.1471-4159.2000.740564.x  PMID:10646507
    • Bohn, L. M., Belcheva, M. M., Coscia, C. J. Mu-opioid agonist inhibition of kappa-opioid receptor-stimulated extracellular signal-regulated kinase phosphorylation is dynamin-dependent in C6 glioma cells Journal of Neurochemistry  2000 74:574-581  DOI:10.1046/j.1471-4159.2000.740574.x  PMID:10646508
    • Xu, F., Gainetdinov, R. R., Wetsel, W. C., Jones, S. R., Bohn, L. M., Miller, G. W., Wang, Y. M., Caron, M. G. Mice lacking the norepinephrine transporter are supersensitive to psychostimulants Nature Neuroscience  2000 3:465-471  PMID:10769386
    • Bohn, L. M., Lefkowitz, R. J., Gainetdinov, R. R., Peppel, K., Caron, M. G., Lin, F. T. Enhanced morphine analgesia in mice lacking beta-arrestin 2 Science  1999 286:2495-2498  DOI:10.1126/science.286.5449.2495  PMID:10617462
    • Gainetdinov, R. R., Bohn, L. M., Walker, J. K. L., Laporte, S. A., Macrae, A. D., Caron, M. G., Lefkowitz, R. J., Premont, R. T. Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice Neuron  1999 24:1029-1036  DOI:10.1016/s0896-6273(00)81048-x  PMID:10624964
    • Ignatova, E. G., Belcheva, M. M., Bohn, L. M., Neuman, M. C., Coscia, C. J. Requirement of receptor internalization for opioid stimulation of mitogen-activated protein kinase: Biochemical and immunofluorescence confocal microscopic evidence Journal of Neuroscience  1999 19:56-63  PMID:9870938  PMCID:PMC2504521
    • Pan, E. C., Bohn, L. M., Belcheva, M. M., Thomas, G. E., Manepalli, A. N., Mamone, J. Y., Johnson, F. E., Coscia, C. J. Kappa-opioid receptor binding varies inversely with tumor grade in human gliomas Cancer  1998 83:2561-2566  DOI:10.1002/(sici)1097-0142(19981215)83:12<2561::aid-cncr23>3.0.co;2-h  PMID:9874464
    • Belcheva, M. M., Bohn, L. M., Ho, M. T., Johnson, F. E., Yanai, J., Barron, S., Coscia, C. J. Brain opioid receptor adaptation and expression after prenatal exposure to buprenorphine Developmental Brain Research  1998 111:35-42  DOI:10.1016/s0165-3806(98)00117-5  PMID:9804882
    • Bohn, L. M., Belcheva, M. M., Coscia, C. J. Evidence for kappa- and mu-opioid receptor expression in C6 glioma cells Journal of Neurochemistry  1998 70:1819-1825  PMID:9572265  PMCID:PMC2571951
  • news release

    • The search for the perfect painkiller The Guardian. 2018
    • New painkillers could thwart opioids’ fatal flaw Science. 2017

featured in

  • America's Long-Overdue Opioid Revolution is Finally Here - The Smithsonian Magazine  News Release
  • Biased for benefit: Stimulating the world's most popular drug targets with more nuance - Nature Medicine  News Release
  • Compound Offers Pain Relief without the Complications - Scientific American  News Release
  • If DEA blocks kratom, promising research on opioid alternative may suffer- PBS News Hour  News Release
  • Kratom Drug Ban May Cripple Promising Painkiller Research - Scientific American  News Release
  • Medicinal Chemistry: New lead for pain treatment - Nature News  News Release
  • Natural Pain-Killing Chemical Synthesized: Making conolidine in the lab could further drug research - US News & World Report  News Release
  • New opioids could relieve pain without dangerous side effects - CNBC  News Release
  • Novel compound to alleviate pain and itch discovered - Science Daily  News Release
  • Palm Beach County scientists: Promising addiction treatment discovery - Palm Beach County Post  News Release
  • Scientists Engineer An Opioid That May Reduce Pain With Less Risk - NPR Morning Edition  News Release
  • Scripps Research Institute Scientists Develop Promising Drug Candidates for Pain, Addiction  News Release
  • The search for a painkiller that works without danger of addiction - The Washington Post  News Release
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Research

research overview

  • G protein coupled receptor (GPCR) signaling is regulated by β-arrestins. β-arrestins are intracellular scaffolding proteins that bind to and regulate activated receptors. The β-arrestins either prevent or enhance GPCR coupling to intracellular signaling molecules. Our work has shown that the role a β-arrestin plays in vivo depends upon the chemical structure of the agonist as well as the location of the receptor. In other words, β-arrestins may turn off signaling of a receptor in one tissue, but may facilitate signaling in another. Further, one agonist may elicit the dampening effects of βarrestins while another agonist may promote a pro-signaling interaction with β-arrestins.

    Our primary interest is in understanding how the regulation of GPCRs can ultimately determine physiological responsiveness to neurotransmitters and pharmaceutics in vivo. We utilize multidisciplinary approaches to assess drug-induced changes in behaviors and physiologies, which we then link to altered receptor-mediated signal transduction cascades in tissues and in primary cultures. Our ultimate goal is to improve drug therapy and to eliminate side effects. We have two major receptor focus areas:

    1. We assess opioid receptor function to determine how these receptors can be tweaked to improve pain therapy. Our efforts focus on dissecting receptor regulation in vivo. This may prove to be a pivotal point at which we can fine-tune receptor signaling to improve pain relief while preventing tolerance, dependence, addiction, respiratory suppression and constipation.

    2. We study serotonin 2A receptors to determine how they may function differently in response to serotonin versus compounds that induce hallucinations with the hopes of improving treatment options for depression and schizophrenia.

    We are very interested in drug development and work closely with medicinal and synthetic chemists as well as researcher in the Drug Discovery group at TSRI.

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Teaching

advisees

  • graduate advising relationship

    • Ho, Jo-Hao (Andre), Ph.D.  candidate, 2013 - 2017
  • postdoc or fellow advising relationship

    • Ho, Jo-Hao (Andre), Ph.D.  candidate, 2017 - 2018
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Service

organizer of event

  • Gordon Research Conference on Molecular Pharmacology 2019
  • Keystone Conferences “G Protein-Coupled Receptors: Structure, Signaling and Drug Discovery” (co-organizers: Arthur Christopoulos and Dominic Behan) 2016
  • Lorentz Workshop “Exploring the biology of GPCRs: bridging biochemistry, therapeutics and physiology.” (co-organizers: Paul Taghert, Michael Nitabach, Martin Lohse and Martine Smit). 2014
  • 4th GPCR Colloquium (co-organizers: Graeme Milligan and Roger Sunahara) Following ASPET/Experimental Biology, April, 2013, in Boston, MA. 2013

professional service activities

  • Faculty of 1000 Basic research in pain. 2014 -
  • Institutional Animal Care and Use Committee (IACUC) TSRI Vice-Chair 2013 -
  • Graduate Education Self Evaluation Chair, Scripps Florida Theme Committee 2012 -
  • Mencuro Therapeutics, Inc. Co-Founder 2010 -
  • The American Society for Biochemistry and Molecular Biology Serves on the editorial board for the Journal of Biological Chemistry. 2013 - 2018
  • American Society for Pharmacology and Experimental Therapeutics Program committee member 2015 - 2017
  • American Society for Pharmacology and Experimental Therapeutics Chair, Neuropharmacology Diviion 2013 - 2015
  • American Society for Pharmacology and Experimental Therapeutics MiniReview editor for Molecular Pharmacology 2010 - 2013
  • National Institutes of Health MDCN - Molecular, Cellular and Developmental Neuroscience Integrated Review Group (MNPS) Member 2009 - 2013
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Background

education and training

  • Ph.D. in Biochemistry & Molecular Biology, Saint Louis University , School of Medicine, with Dr. Carmine Coscia 1999
  • B.A. in Chemistry, Virginia Polytechnic Institute and State University , Cum Laude, research mentor: Neil Castignoli, Jr., Ph.D. 1993
  • B.S. in Biochemistry, Virginia Polytechnic Institute and State University , Cum Laude, research mentor: David Bevan, Ph.D. 1993

awards and honors

  • The Charles E. Smith Annual Memorial Lecture, The National Institute for Psychobiology in Israel, Jerusalem, Israel, 2019
  • Coy W. Waller Distinguished Lecture at the University of Mississippi, 2019
  • "The Opioid Crisis: What Solutions can Science Contribute," ACNP, President's Plenary, 2018
  • The Viktor Mutt Lectureship, conferred by International Regulatory Peptide Society, 2018
  • University of Texas Medical Branch Student-Invited NIDA Distinguished Lecture, 2017
  • West Virginia University T32 Training Grant Student-Invited Keynote Speaker, 2017
  • Creighton University School of Medicine Distinguished Lecturer, 2016
  • The 2016 Dennis Feller Distinguished Lectureship, conferred by The Ohio State University College of Pharmacy, 2016
  • Faculty of 1000: Pain, 2015
  • John J. Abel Award, conferred by American Society for Pharmacology and Experimental Therapeutics, 2011
  • Joseph Cochin Young Investigator Award , conferred by College on Problems of Drug Dependence, 2009
  • Featured as one of “30 in Their 30s” by BioOhio, “The Voice of Bioscience in Ohio”, conferred by BioOhio, 2007
  • 2005 Committee on Women in Neuroscience Career Development Award, conferred by Sponsored by the Society for Neuroscience and Merck, 2005
  • Career Development Award, conferred by Society for Neuroscience, 2005
  • School of Biomedical Sciences Award for Excellence in Research, conferred by The Ohio State University, 2005
  • Postdoctoral Research Award, conferred by Joint University of North Carolina - Chapel Hill and Duke University Cell and Developmental Biology Retreat, 2002
  • Early Career Investigator Award, conferred by College on Problems of Drug Dependence, 2002
  • Graduate Student Association Award for Research Excellence, 1996
  • Ruth L. Kirschstein National Research Service Award, conferred by National Institutes of Health, 2000 - 2002
  • Ruth L. Kirschstein National Research Service Award, conferred by National Institutes of Health, 1996 - 1999
  • Elected Chair of the 2019 Gordon Conference on Molecular Pharmacology
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Contact

full name

  • Laura Michelle Bohn

geographic location

  • Scripps Florida 
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Identity

ORCID iD

  • ORCID iD http://orcid.org/0000-0002-6474-8179

ResearcherID (Thomson Reuters)

  • A-7483-2014

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