Protein chemistry and peptide synthesis have been a prominent feature of the Program's activities since its inception in 1968. Originally, these were carried out as a part of a component Project aimed at the structural analysis and study of the structure-activity relations of parathyroid hormone and calcitonin. Besides the earliest active synthetic calcium-regulating peptides, fundamental and enduring contributions to sequencing and synthetic methodologies emerged from these investigations. The increasing versatility of these chemical methods brought steadily expanding benefits to all of the projects;to meet the resulting needs, a separate Core was established in 1979. In addition to continued development of synthetic PTH agonists and antagonists, the Core proceeded to fulfill such diverse roles as identifying products of in vivo PTH metabolism, calibrating standards for a range of biological and immunological assays, characterizing and microsequencing recombinant expression products and biosynthetically labeled proteins, and characterizing membrane proteins in conjunction with the successful effort to purify the PTH/PTHrP receptor. With the move of the Endocrine Unit into the Wellman (now Their) Building laboratory in the mid-1980's came the first step in the process of resource sharing that continues to this day to bring major benefits to both the Program and the NIH. By formally consolidating in 1993 into a common analytical-synthesis facility with the Molecular Endocrinology and Reproductive Endocrine Units, followed by the Partners AIDS Research Center, the Core gained important new capabilities including gas-phase sequencing, microbore HPLC and enhanced synthesis capacity. Then, as now, operating costs were carefully allocated among the individual projects and investigators according to utilization, but the benefits realized from widened access to methodology, depth of experience, flexibility in personnel deployment and economies of scale were clearly apparent at the time of the last Program Project renewal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK011794-45
Application #
8565028
Study Section
Special Emphasis Panel (ZDK1-GRB-9)
Project Start
Project End
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
45
Fiscal Year
2013
Total Cost
$181,477
Indirect Cost
$79,777
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Christov, Marta; Clark, Abbe R; Corbin, Braden et al. (2018) Inducible podocyte-specific deletion of CTCF drives progressive kidney disease and bone abnormalities. JCI Insight 3:
Dedic, Christopher; Hung, Tin Shing; Shipley, Alan M et al. (2018) Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes. Bone 116:135-143
Mizuhashi, Koji; Ono, Wanida; Matsushita, Yuki et al. (2018) Resting zone of the growth plate houses a unique class of skeletal stem cells. Nature 563:254-258
Hanna, Patrick; Grybek, Virginie; Perez de Nanclares, Guiomar et al. (2018) Genetic and Epigenetic Defects at the GNAS Locus Lead to Distinct Patterns of Skeletal Growth but Similar Early-Onset Obesity. J Bone Miner Res 33:1480-1488
Wein, Marc N; Foretz, Marc; Fisher, David E et al. (2018) Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential. Trends Endocrinol Metab 29:723-735
Bastepe, Murat (2018) GNAS mutations and heterotopic ossification. Bone 109:80-85
Roszko, Kelly L; Bi, Ruiye; Gorvin, Caroline M et al. (2017) Knockin mouse with mutant G?11 mimics human inherited hypocalcemia and is rescued by pharmacologic inhibitors. JCI Insight 2:e91079
Grigelioniene, Giedre; Nevalainen, Pasi I; Reyes, Monica et al. (2017) A Large Inversion Involving GNAS Exon A/B and All Exons Encoding Gs? Is Associated With Autosomal Dominant Pseudohypoparathyroidism Type Ib (PHP1B). J Bone Miner Res 32:776-783
Balani, Deepak H; Ono, Noriaki; Kronenberg, Henry M (2017) Parathyroid hormone regulates fates of murine osteoblast precursors in vivo. J Clin Invest 127:3327-3338
Cheloha, Ross W; Chen, Bingming; Kumar, Niyanta N et al. (2017) Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone Receptor with Broad ? Residue Distribution. J Med Chem 60:8816-8833

Showing the most recent 10 out of 215 publications