After his internship, Larry became an instructor in Homer Smith’s physiology department at NYU and worked with him at the Mount Desert Island Biological Laboratory in Maine, studying electrolyte regulation in animals and translating the www.selleckchem.com/products/ipi-145-ink1197.html findings to humans. After further training in clinical nephrology, Larry became Chief of the Renal Section at the Boston VA 1954-1956, and then Assistant Professor of Medicine, SUNY College of Medicine, Syracuse. In 1960–1961 he took the first of his several highly productive

sabbaticals, this time to the Strangeways Research Laboratory in Cambridge, UK, where he learned bone rudiment organ culture from Dame Honor Fell and developed it into a quantitative method to study effects of agents on bone by labelling the fetal bones in vivo with 45Ca. Larry became fully dedicated Selleckchem DZNeP to bone upon taking a position at the University of Rochester as Associate Professor of Clinical Pharmacology and Medicine. Larry spent 13 years at Rochester, and was part of a visionary group of “boneheads” that included Bill Neuman and Bill Peck. Larry

used the bone organ cultures to demonstrate that parathyroid hormone stimulated bone resorption by direct effects on bone. He guided studies in his laboratory that showed the role of cAMP in resorption, the direct effects of calcitonin to inhibit resorption, and the secretion of bone-resorbing activity from cultured parathyroid glands. Other studies addressed effects of steroid hormones, including the newly discovered vitamin D metabolites. Discoveries that he was to pursue extensively with his students and Inositol oxygenase colleagues throughout his career were the effects of newly recognized factors, prostaglandins, growth factors and cytokines. To expand his experience to the anabolic side

of bone, Larry took a sabbatical at the National Institutes of Dental Research with George Martin and Karl Piez to learn collagen chemistry, and as a side interest worked with John Horton and Joel Oppenheim in the immunology group at NIDR and discovered that the active inflammatory material from periodontal disease contained a bone resorbing factor that they named Osteoclast Activating Factor. Larry’s further work in what was eventually named “osteoimmunology” was stimulated by the collaboration with the late Greg Mundy, inspiring and leading research on myeloma bone disease when they showed that OAF was produced by supernatants of both lymphoid and myeloma cell cultures. Subsequent work over many years showed that OAF was a composite of several bone-resorbing cytokines. Larry moved to Connecticut in 1974 as Chief of Endocrinology at the University of Connecticut Health Centre and was a major force in developing that institution as a center for bone research.