Laura M. Bohn, Ph.D.

Associate Professor
Department of Pharmacology

Degree: St. Louis University School of Medicine
Post-Doctoral Training: Duke University Medical Center, Cell Biology & HHMI, Dr. Marc Caron

Contact Information
798 Biomedical Research Tower
460 W. 12th Avenue
Columbus, OH  43210
PHONE: (614) 292-1303
FAX: (614) 292-7544
E-MAIL: bohn.24@osu.edu

Link to NLM PubMed publications list for Laura M. Bohn (last 10 years)

Research Area:

The research in my lab spans from G protein coupled receptor (GPCR) signal transduction in cell culture systems to behavioral consequences of that signaling in genetically modified mouse models. My work focuses primarily on the regulation of opioid receptor signaling.  This is an important neurotransmitter system in that opioid receptor signaling plays a very prominent role in neuronal systems of pain perception as well as in peripheral responses throughout the body, including digestion, respiration, and immune response.  To date, my major focus has been on the mu opioid receptor (mOR) type, the primary target for the opiate narcotic, morphine.  The binding of morphine to the mOR is the first step leading to analgesia.  Understanding the mechanisms whereby this receptor is regulated can provide insight, not only to controlling pain, but can also lead to an understanding of the cellular mechanisms underlying opiate tolerance, dependence, and addiction.

Current Research:

Our laboratory is committed to understanding how the molecular regulation of G protein coupled receptors (GPCR) can translate to overall drug responsiveness in vivo.  We focus on the regulation of the mu opioid receptor and this can determine behavioral and physiological responses to the opiate narcotic drugs, such as morphine.

Morphine, and the related opiates fentanyl, methadone, and oxycodone are potent pain relievers and mediate their analgesic effects primarily by activation of the mu opioid receptor.  However, these drugs produce many unwanted drug effects as well, including constipation and respiratory suppression.  Long-term use of opiates can produce drug tolerance, physical dependence and, in some cases, drug addiction. 

Our focus has been to determine how GPCR regulatory mechanisms could play a role in determining the variety of biological responses a single drug can elicit.  For example, we have asked: If morphine activates the mu opioid receptor, are the signal transduction pathways that determine opiate-induced pain relief the same as those that determine opiate-induced constipation?  Our second question is: If the signaling if different for these two distinct biological responses could the variation be delineated at the point of receptor regulation?

To address these questions we have employed an extensive array of physiological and behavioral measurements in genetically modified mouse models.  Our mouse models lack certain regulatory components that are involved in GPCR desensitization and GPCR signaling.  A model of GPCR regulation is shown in Figure 1.  Upon activation, the receptor signals by coupling to a G protein and this activates a downstream signaling cascade which ultimately results in the biological response.  The receptor can then be turned off by GPCR kinase (GRK)-mediated phosphorylation followed by the subsequent binding of Beta-arrestin (barrestin) proteins.  This process is a fundamentally conserved process for desensitizing most GPCRs; however, some GPCRs can signal via other pathways upon binding barrestin, independently of the G protein interaction.

We want to know how the GRK and barrestin interactions with the receptor can determine the degree of biological response mediated by the drug actions at the receptor.  We use mice that have genetic deletions of GRKs (GRK3, GRK4, GRK5, and GRK6; heterozygotes for GRK2) and barrestin-2.  In earlier work performed at Duke University under the training of Dr. Marc Caron and in collaboration with Dr. Robert Lefkowitz, we found that mice lacking barrestin2 have greater analgesic responses to morphine with very little opiate-tolerance.  We have expanded these studies and have recently found that while the morphine-induced pain relief is greater; these mice experience less morphine-induced constipation and very little respiratory suppression.

We are currently trying to understand the role of barrestin2 in mediating morphine-induced constipation and respiratory suppression.  One of our major goals is to exploit the GPCR regulatory components for the development of novel therapeutics that may provide greater pain relief with limited narcotic side effects.