Assistant Professor
MCRI and Pharmacology
New England Medical Center
750 Washington Street
Boston, MA 02111
Phone: 617-636- 7740
Email: Mbeinborn@Lifespan.org

For the most recent description of Dr. Beinborn's research and citations, please click on:
Dr. Beinborn's Lab Page: www.nemc.org/mcri/pharmacologyfocusbeinborn.htm or www.nemc.org/mcri/pharmacology.htm

Research Interests:

Dr. Beinborn's research interests focus primarily on the molecular processes that lead to ligand-induced activation of peptide hormone receptors, and the downstream triggering of intracellular signaling cascades. As a model system to explore the underlying mechanisms, he has been working over the past several years on the G-protein coupled receptors (GPCRs) for the gastrointestinal hormone/neurotransmitter cholecystokinin (CCK). Mutational analysis of recombinant CCK receptors lead to the identification of two distinct yet interacting processes that determine agonist-induced receptor activation: (i) ligand-specific interactions at selected amino acids within a putative receptor transmembrane domain binding pocket, and (ii) the equilibrium set point between "active" and "inactive" receptor conformations. It is of note that there is evidence for multiple '"active" receptor conformations that may be differentially activated by a given CCK receptor ligand and that can lead to the selective stimulation of different intracellular second messenger systems (e.g., inositol phosphate formation vs. cAMP production).

More recently, Dr. Beinborn has begun to explore to what extent these general principles as developed for CCK receptors (categorized as class A, rhodopsin-type GPCRs) are applicable to members of the class B subfamily of receptors (which share a seven transmembrane domain topology yet have no sequence homology with class A proteins). The latter studies focus on the receptors for glucagon-like peptides (GLP) which are important physiological regulators of blood glucose levels, satiety, and resorption of nutrients through the intestinal mucosa. Specific projects that are currently pursued using a combination of biochemical, molecular biology, and cell biology techniques include the following: (i) to identify amino acids, both in the GLP-1 receptor and in its peptide ligands, that are triggers of second messenger signaling; (ii) to investigate compatibility of GLP-1 receptor stimulation with the "extended trenary model", a molecular theory of receptor activation that has been formulated based on class A receptor function, and (iii) to explore the mechanisms underlying tonic activity of the GLP-1 receptor when this protein is expressed in the context of highly differentiated pancreatic beta cells. These studies will facilitate the discovery of novel non-peptide agonist drugs, and may also provide important clues regarding how to genetically engineer pancreatic beta cell lines as a potential treatment of diabetes.

Recent Publications:

Beinborn M, Worrall CI, McBride EW, Kopin AS. A human glucagon-like peptide-1 receptor polymorphism results in reduced agonist responsiveness. Regulatory Peptides 2005;130:1-6.

Masur K, Tibaduiza EC, Chen C, Ligon B, Beinborn, M. Basal receptor activation by locally produced glucagon-like peptide-1 contributes to maintaining beta-cell function. Molecular Endocrinology 2005;19:1373-1382.

Takabayashi T, Shimizu S, Clark BD, Beinborn M, Burke JF, Gelfand JA. Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells. Surgery 2004;135:544-554.