The National Institute of Diabetes & Digestive & Kidney Diseases

1) Conducts research aimed at obtaining and characterizing progenitors of the cells of the human endocrine pancreas (islets of Langerhans) including insulin-producing beta cells, glucagon-producing alpha cells, somatostatin-producing delta cells and pancreatic polypeptide-producing cells, and using them in an attempt to develop approaches to cell replacement therapy for patients with diabetes mellitus.

2) Studies the structure-function relationships of G protein-coupled receptors; in particular, receptors for thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH)and medium- and long-chain fatty acids.

1. Tikhonova IG, Sum CS, Neumann S, Thomas CJ, Raaka BM, Costanzi S, Gershengorn MC Bidirectional, Iterative Approach to the Structural Delineation of the Functional "Chemoprint" in GPR40 for Agonist Recognition. J Med Chem(50): 2981-9, 2007. [Full Text/Abstract]

2. Morton RA, Geras-Raaka E, Wilson LM, Raaka BM, Gershengorn MC Endocrine precursor cells from mouse islets are not generated by epithelial-to-mesenchymal transition of mature beta cells. Mol Cell Endocrinol(270): 87-93, 2007. [Full Text/Abstract]

3. Jaschke H, Neumann S, Moore S, Thomas CJ, Colson AO, Costanzi S, Kleinau G, Jiang JK, Paschke R, Raaka BM, Krause G, Gershengorn MC A low molecular weight agonist signals by binding to the transmembrane domain of thyroid-stimulating hormone receptor (TSHR) and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). J Biol Chem(281): 9841-4, 2006. [Full Text/Abstract]

4. Moore S, Jaeschke H, Kleinau G, Neumann S, Costanzi S, Jiang JK, Childress J, Raaka BM, Colson A, Paschke R, Krause G, Thomas CJ, Gershengorn MC Evaluation of small-molecule modulators of the luteinizing hormone/choriogonadotropin and thyroid stimulating hormone receptors: structure-activity relationships and selective binding patterns. J Med Chem(49): 3888-96, 2006. [Full Text/Abstract]

5. Engel S, Neumann S, Kaur N, Monga V, Jain R, Northup J, Gershengorn MC Low affinity analogs of thyrotropin-releasing hormone are super-agonists. J Biol Chem(281): 13103-9, 2006. [Full Text/Abstract]

6. Wei C, Geras-Raaka E, Marcus-Samuels B, Oron Y, Gershengorn MC Trypsin and thrombin accelerate aggregation of human endocrine pancreas precursor cells. J Cell Physiol(206): 322-8, 2006. [Full Text/Abstract]

7. Jiang JK, Thomas CJ, Neumann S, Lu X, Rice KC, Gershengorn MC  1-(Phenyl)isoquinoline carboxamides: a novel class of subtype selective inhibitors of thyrotropin-releasing hormone (TRH) receptors.  Bioorg Med Chem Lett (15): 733-6, 2005. [Full Text/Abstract]

8. Huang W, Osman R, Gershengorn MC  Agonist-induced conformational changes in thyrotropin-releasing hormone receptor type I: disulfide cross-linking and molecular modeling approaches.  Biochemistry (44): 2419-31, 2005. [Full Text/Abstract]

9. Du D, Raaka BM, Grimberg H, Lupu-Meiri M, Oron Y, Gershengorn MC Carboxyl tail cysteine mutants of the thyrotropin-releasing hormone receptor type 1 exhibit constitutive signaling: role of palmitoylation. Mol Pharmacol(68): 204-9, 2005. [Full Text/Abstract]

10. Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM  Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells.  Science (306): 2261-4, 2004. [Full Text/Abstract]