Dr. Lawrence Toll’s research focuses on the management of pain and drug addiction through pharmacology and new drug discovery. His basic research on opioid and NOP systems, and nicotinic acetylcholine receptors, as well as his identification and characterization of endogenous neuropeptides, have opened new avenues of research and identified novel drug targets. In collaboration with medicinal chemists, Dr. Toll seeks to explore basic mechanisms and the biochemical basis of chronic pain and drug addiction, and to identify novel medications for both disorders.
Dr. Lawrence Toll earned his Ph.D. in Biological Chemistry at UCLA in 1978. He stayed on at UCLA as a postdoctoral fellow in Biological Chemistry through 1979 at which time he accepted a second postdoctoral fellowship in Pharmacology at Johns Hopkins University in Maryland. In 1981, Dr. Toll joined SRI International in Menlo Park, California, as a Senior Receptor Pharmacologist and then became Program Director and ultimately Senior Director of the Neuropharmacology Program at SRI International. Dr. Toll’s research took him to France in 1994-1995 and again in 2004-2005 where he worked as a Visiting Scientist, first in the Laboratoire de Pharmacologie et de Toxicologie Fondamentales, Centre National de la Recherche Scientifique in Toulouse, France, and then at the University of Louis Pasteur, Institut de Génétique et de Biologie Moléculaire et Cellulaire in Strasbourg, France. In 2011, Dr. Toll joined Torrey Pines Institute for Molecular Studies as a Full Member and Director of Neuropharmacology. He is internationally recognized as the co-discoverer of the endogenous neuropeptide, nociceptin. Dr. Toll’s work has been chronicled in over 90 publications.
- December 1973: B.A. in Chemistry - University of California, San Diego
- April 1978: Ph.D. in Biological Chemistry - UCLA, Thesis advisor Dr. Bruce Howard
- 1/73-9/74: Laboratory assistant for Dr. Russell Doolittle, Department of Chemistry, UCSD.
- 5/78-8/79: Postdoctoral Fellow for Dr. Bruce Howard, Department of Biological Chemistry, UCLA.
- 9/79-10/81: Postdoctoral Fellow for Dr. Solomon Snyder, Department of Neuroscience, Johns Hopkins University School of Medicine.
- 11/81-12/89: Sr. Receptor Pharmacologist, Molecular Theory Department, SRI International.
- 1/90-present: Sr. Director, Neuropharmacology Program, Pharmaceutical Discovery Division, SRI International.
- 8/94-8/95: Visiting scientist, Laboratoire de Pharmacologie et de Toxicologie Fondamentales, Centre National de la Recherche Scientifique, Toulouse, FRANCE.
- 1/02-12/07: Director, Biological Sciences Department, Biosciences Division, SRI International
- 8/04-8/05: Visiting scientist, University Louis Pasteur, IGBMC, Strasbourg, FRANCE.
- 1/08-8/11: Co-Director, Neuroscience Department, Biosciences Division, SRI International
- 8/11-present: Director, Neuropharmacology Program, Torrey Pines Institute for Molecular Studies
- Society for Neuroscience
- College for Problems of Drug Dependence
- International Narcotics Research Conference - Member Executive Committee, Vice president/Treasurer elect
- Member, Chinese Chemical Society
- Pharmacology and molecular biology of opioid and NOP systems.
- Discovery and development of pharmacotherapies for the treatment of pain and addiction
- Identification and characterization of endogenous neuropeptides as novel drug targets
- Nicotinic acetylcholine receptors and their involvement in nicotine dependence
- Translational research
Selected Publications (10 of 74)
- TV Khroyan, WE Polgar, J Orduna, J Montenegro, F Jiang, NT Zaveri, L Toll. Differential Effects of NOP Receptor Agonists in Acute versus Chronic Pain: Studies with Bifunctional NOP/mu Receptor Agonists in the Sciatic Nerve Ligation Chronic Pain Model in Mice. J Pharmacol Exp Ther. 2011 Aug 22. [Epub ahead of print]
- TV Khroyan, WE Polgar, G Cami-Kobeci, SM Husbands, NT Zaveri, L Toll. The first universal opioid ligand, (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028): characterization of the in vitro profile and in vivo behavioral effects in mouse models of acute pain and cocaine-induced reward. J Pharmacol Exp Ther. 2011 336:952-61.
- N. Zaveri, F Jiang, C Olsen, W. Polgar, L Toll. Novel α3β4 nicotinic acetylcholine receptor-selective ligands. Discovery, structure-activity studies, and pharmacological evaluation. J Med Chem. 2010 53:8187-91.
- K. Jozwiak, AY Woo, MJ Tanga, L Toll, L Jimenez, JA Kozocas, A Plazinska, RP Xiao, IW Wainer IW. Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective beta(2)-adrenergic receptor agonists. Bioorg Med Chem. 2010 18:728-36.
- L. Toll, T.V. Khroyan, W. Polgar, F. Jiang, C. Olsen, N.T. Zaveri. Comparison of the Anti-nociceptive and Anti-Rewarding Profiles of Novel Bifunctional Nociceptin/Orphanin FQ Receptor (NOPr)-Mu Opioid Receptor (MOPr) Ligands: Implications for Therapeutic Applications. J Pharmacol Exp Ther. 2009 331:954-64.
- T.V. Khroyan, W.E. Polgar, F. Jiang, N.T. Zaveri, L. Toll. NOP Receptor Activation Attenuates Antinociception Induced by Mixed NOP/Mu-Opioid Receptor Agonists. J Pharmacol Exp Ther. 2009 331:946-53.
- K. Sonmez, N.T. Zaveri, I.A. Kerman, S. Burke, C.R. Neal, X. Xie, S.J. Watson, L. Toll. Evolutionary sequence modeling for discovery of peptide hormones. PLoS Comput Biol. 2009 Jan;5(1):e1000258. Epub 2009.
- L. Toll, I.P. Berzetei-Gurske, W.E. Polgar, S.R. Brandt, I.D. Adapa, L. Rodriguez, R. W. Schwartz, D. Haggart, A. O’Brien, A. White, J. M Kennedy, K. Craymer, L. Farrington, J.S. Auh . Standard binding and functional assays related to Medications Development Division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res. Monograph, 178, The College on Problems of Drug Dependence, 59th Annual Meeting,, 1998, pp. 440-466.
- J.-C. Meunier, C. Mollereau, L. Toll, C. Suaudeau, C. Moisand, P. Alvinerie, J.-L. Butour, J.-C. Guillemot, P. Ferrara, B. Monsarrat, H. Mazarguil, G. Vassart, M. Parmentier, and J. Costentin. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature. 377, 532-535, 1995.
- L. Toll, C. B. Gundersen, Jr., and B. D. Howard. Energy utilization in the uptake of catecholamines by synaptic vesicles and adrenal chromaffin granules. Brain Res. 136, 59-66 (1977).
- Inventors: Ronald G. Almquist, Lawrence Toll. Isolated atrial peptide-degrading enzyme and novel compounds useful as inhibitors thereof. Patent number: 5262521. Issue date: Nov 16, 1993
- Inventors: Lawrence Toll, Patrick Denis Lincoln, Peter D. Karp, Kemal Sonmez. Biopolymer sequence comparison. Patent number: 7133781. Issue date: Nov 7, 2006
- Inventors: Kemal Sonmez, Lawrence Toll, Patrick Denis Lincoln, Peter D. Karp. Data relationship model. Patent number: 7039238. Issue date: May 2, 2006
- Pending: Inventors: Lawrence R. TOLL, David C. Yeomans, Martin S. Angst, Daniel I. Jacobs. METHODS FOR TREATMENT OF PAIN. Application number: 12/844,721. Publication number: US 2011/0021426 A1. Filing date: Jul 27, 2010
- Pending: Inventors Faming Jiang, Taline Khroyan, Cris M. Olsen, Willma E. Polgar, Lawrence R. Toll, Nurulain T. Zaveri. Nicotinic Acetylcholine Receptor Modulators. Application number: 11/934,583. Publication number: US 2009/0118326 A1. Filing date: Nov 2, 2007
Honors & Awards
- Winner of 2002 SRI Fellowship Award for Research Excellence
- International Narcotics Research Conference Executive Committee 2002-2005
- International Narcotics Research Conference Chair Local Organizing
- Program Committee, 2002, International Narcotics Research Conference Treasurer, 2011-Present