Genetics of Bone Biology and Skeletal Disease

Professor Thakker has been May Professor of Medicine since 1999 and heads a group of scientists that investigate the pathophysiology of human diseases. This team has carried out analyses of more than 15 disorders, with identification of defective genes and functional studies that explain disease phenotypes. This resulted in the elucidation of signaling and regulatory pathways downstream of the calcium-sensing receptor and their physiological relevance; molecular mechanisms of endocrine tumor formation and potential new therapeutic targets; and molecular and cellular aspects of renal tubular physiology. Professor Thakker’s work has been internationally recognized and received awards including the Louis V. Avioli Founder’s Award from the ASBMR; the Parathyroid Medal from the FRB; the Jack W. Coburn Endowed Lectureship from the ASN; the International Research Prize from the ASBMR; and the Dale Medal from the Society for Endocrinology. Professor Thakker was elected a Fellow of the Royal Society in 2014. Michael P. Whyte, M.D. is Professor of Medicine, Pediatrics, and Genetics at the Washington University School of Medicine, a staff member of Barnes-Jewish Hospital and St. Louis Children’s Hospital, and Medical-Scientific Director at the Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children in St. Louis, Missouri. Dr. Whyte’s research interests include the cause, outcome, and treatment of heritable disorders of bone and mineral metabolism in children and adults. Included are genetic forms of rickets such as hypophosphatasia and X-linked hypophosphatemia, brittle bone diseases like osteogenesis imperfecta, conditions that cause dense bones such as osteopetrosis, and disorders of accelerated skeletal turnover including juvenile Paget’s disease. Dr. Whyte has authored or coauthored more than 300 scientific papers or book chapters concerning these disorders. John Eisman AO is Director of Clinical Translation and Advanced Education at Garvan. From 1984 to December 2011, he was Garvan's Director of Osteoporosis and Bone Biology. Professor Eisman was Editor-in-Chief of the Journal of Bone and Mineral Research, is a past member of the Board of the International Bone and Mineral Society and of the Council of the American Society for Bone and Mineral Research. He is a co-founder and past-President of the Australia and New Zealand Bone and Mineral Society. The focus of Professor Eisman’s research is the epidemiology and genetics of osteoporosis, encompassing population, family, and twin studies as well as molecular and cellular mechanisms for gene effects. His major commitment and focus are translating osteoporosis research findings to real improvements in health care delivery to the general community through the education of patients and their doctors. Takashi Igarashiworks in the Department of Pediatrics, Faculty of Medicine, The University of Tokyo, Mejirodai, Japan.

• Part 1: General background to genetics and ‘omics1. Introduction to genetics of skeletal and mineral metabolic diseases2. Genome sequencing and Big Data analysis3. Genome-wide association studies in bone mineral density: principles, practicalities, progress, and potential in bone and mineral disorders, including osteoporosis4. Functional genomics5. Epigenetics6. Bone-on-chip models7. Mouse models: approaches to generate in vivo models for hereditary disorders of mineral and skeletal homeostasis8. Bone quality characteristics in zebrafish disease models9. Prospects of gene therapy for skeletal diseases10. Genetics and pharmacogenetics of osteoporosis: personalized medicine outlookPart 2: General background to bone biology11. Biology of bone and cartilage12. Overview of bone structure and strength13. Overview of joint and cartilage biology14. Osteocyte biology15. Bone marrow stromal cells/skeletal stem cells16. Osteoimmunology17. Genetics of bone fat and energy regulation18. Central regulation of bone remodeling, genetic evidence19. Integrating endocrine and paracrine influences on bone: lessons from parathyroid hormone and parathyroid hormone-related protein20. The fibroblast growth factor-Klotho endocrine system in health and disease21. Mechano-adaptation and mechano-sensing in skeletal biology22. The hypoxia signaling pathway in the skeleton23. Chronobiology and clock genes in bone and mineral metabolism24. Osteoblastic cell senescence and their contribution to metabolic bone diseases25. Fetal control of calcium and phosphate homeostasis26. Control of mineral and skeletal homeostasis during pregnancy and lactationPart 3: Disorders of bone and joint27. Gene discoveries and novel therapies in monogenic low and high bone mass disorders28. Osteogenesis imperfecta29. Osteoarthritis: genetic studies of monogenic and complex forms30. Skeletal dysplasias31. Sclerosing bone dysplasias32. Mendelian disorders of RANKL/RANK/OPG/NF-κB signaling33. Hypophosphatasia and how alkaline phosphatase promotes mineralization34. Fibrodysplasia ossificans progressiva35. The melorheostoses36. Disorders and mechanisms of ectopic calcificationPart 4: Parathyroid and related disorders37. Hyperparathyroidism38. Hypoparathyroidism39. Gsα, pseudohypoparathyroidism, fibrous dysplasia, and McCune-Albright syndrome40. Genetic disorders caused by mutations in the parathyroid hormone/parathyroid hormone-related peptide receptor, its ligands, and downstream effector molecules41. The calcium-sensing receptor42. Multiple endocrine neoplasia syndromes43. Multiple endocrine and other organ neoplasia syndromesPart 5: Vitamin D and renal disorders44. Genetic disorders of vitamin D metabolism and action45. X-linked hypophosphatemias46. Autosomal hypophosphatemias47. Genetics of hypercalciuria and kidney stones