Laura Bohn, Ph.D.
Associate Professor with Tenure
Ph.D., Biochemistry & Molecular Biology, St. Louis University School of Medicine, 1999
Department of Molecular Therapeutics
Department of Neuroscience
The Scripps Research Institute
130 Scripps Way 2A2
Jupiter, Florida 33458
Telephone: 561-228-2227
Fax: 561-228-3081
Email: lbohn@scripps.edu
Research Interests
G protein coupled receptor (GPCR) signaling is regulated by βarrestins. βArrestins are intracellular scaffolding proteins that bind to and regulate activated receptors. The βarrestins, in turn, either prevent or enhance GPCR coupling to intracellular signaling molecules. Our work has shown that the role a βarrestin plays in vivo depends upon the chemical structure of the agonist as well as the physical location of the receptor. In other words, βarrestins 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 facilitative signaling interaction with βarrestins.
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:
- We study 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.
- 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 researchers in the Drug Discovery group at TSRI.
Selected Publications
Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT. (1999). Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science. 286(5449):2495-8.
Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG. (2000). Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature. 408(6813):720-3.
Raehal KM, Walker JK, Bohn LM. (2005). Morphine side effects in beta-arrestin 2 knockout mice. J Pharmacol Exp Ther. 314(3):1195-201. *
Groer CE, Tidgewell K, Moyer RA, Harding WW, Rothman RB, Prisinzano TE, Bohn LM. (2007). An opioid agonist that does not induce mu-opioid receptor-β-arrestin interactions or receptor internalization. Mol Pharmacol. 71(2):549-57. *
Schmid CL, Raehal KM, Bohn LM. (2008). From the Cover: Agonist-directed signaling of the serotonin 2A receptor depends on βarrestin-2 interactions in vivo. Proc Natl Acad Sci U S A. 105(3):1079-84. *
Schmid CL and Bohn LM. (2010) Serotonin, but not N-Methyltryptamines, activates the serotonin 2A receptor via a a βarrestin2/Src/Akt signaling complex in vivo. Journal of Neuroscence.30(40):13513-24. *
Bohn LM and McDonald PH. (2010) Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery. Invited Review for Drug Discovery Today: Technologies, Theme issue: Mechanistic Pharmacology, new developments. 7(1):e37-e42.
Raehal KM and Bohn LM. (2011) The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology..- Special Issue- “When Structure Meets Function.” 60(1):58-65.
Tarselli MA, Raehal KM, Brasher AK, Streicher JM, Groer CE*, Cameron MD, Bohn LM^ and Micalizio GC^. (2011) Synthesis of Conolidine, a Potent Non-Opioid Analgesic for Tonic and Persistent Pain. Nature Chemistry, 3:449–453. ^corresponding authors.
Groer, CE*, Schmid, CL*, Jaeger AM**, and Bohn, LM. (2011) Agonist-directed interactions with specific βarrestins determine mu opioid receptor trafficking, ubiquitination, and dephosphorylation J. Biol. Chem. (ePub ahead of print, July 2011).
* Graduate Student authored publication.
** Undergraduate Trainee authored publication.
Awards, Recognition, Appointments, and Honors
2011 The John J. Abel Award from the American Society of Pharmacology & Experimental Therapeutics and Pfizer
2010-2011 MiniReview Editor for Molecular Pharmacology.
2010 Co-Founder, Director of Scientific Advisory Board, Mencuro Therapeutics, Inc.
2010 Roundtable Discussant and Speaker, Neuropharmacology Conference: High Resolution Neuropharmacology: Structure Changes the Paradigm.
2009-2013 NIH ZRG1 MDCN- Molecular Neuropharmacology and Signaling Study Section (MNPS) Member
2009 The Joseph Cochin Young Investigator Award from the College on Problems of Drug Dependence
2007 Featured as one of “30 in Their 30s” by BioOhio, “The Voice of Bioscience in Ohio”
2006 School of Biomedical Sciences Award for Excellence in Research, The Ohio State University
2005 Committee on Women in Neuroscience Career Development Award, sponsored by the Society for Neuroscience and Merck
2002 College on Problems of Drug Dependence Early Career Investigator Award
2002 Postdoctoral Research Award, Joint University of North Carolina - Chapel Hill and Duke University Cell and Developmental Biology Retreat
2000-02 Ruth L. Kirschstein National Research Service Award (NRSA) Postdoctoral Fellowship (NIDA F32)
1996-99 Ruth L. Kirschstein National Research Service Award (NRSA) Predoctoral Fellowship (NIDA F31)
1997-98 Student Representative to University Board of Governors
1997-98 President, Graduate Student Association
1996 Graduate Student Association Award for Research Excellence
1996-97 Vice President, Graduate Student Association
1993 Graduation: Cum Laude, Virginia Tech