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 Studies4. Epigenetics5. Multi-omics approaches in bone research6. Functional Genomics7. Organ-on-Chips8. Mouse Models: Approaches to Generate In Vivo Models for Hereditary Disorders of Mineral and Skeletal9. Emerging therapeutic approaches (including gene therapy) for Skeletal Diseases10. Pharmacogenetics and Pharmacogenomics of Osteoporosis: Personalized Medicine Outlook11. Drug discovery in the era of cryo-electron microscopy (cryoEM)PART 2: GENERAL BACKGROUND TO BONE BIOLOGY12. Biology of Bone and Cartilage13. Overview of Bone Structure and Strength14. Overview of Joint and Cartilage Biology15. Osteocyte Biology16. Skeletal Stem Cells/Bone Marrow Stromal Cells17. Osteoimmunology18. Senescence in Bone Disease19. Chronobiology and clock genes, relevance to musculoskeletal health20. Mechano-sensing in skeletal biology21. Hypoxia signalling bone and cartilage22. Integrating Endocrine and Paracrine Influences on Bone; Lessons from Parathyroid Hormone and Parathyroid23. Genetics of Bone Fat and Energy Regulation24. The Cross Talk Between the Central Nervous System, Bone, and Energy Metabolism25. 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 disorders.28. Osteoporosis29. Osteogenesis Imperfecta30. Osteoarthritis: Genetic Studies of Monogenic and Complex Forms31. Mendelian Disorders of RANKL/OPG/RANK/NF-κB Signalling32. Skeletal Dysplasias33. Hypophosphatasia and How Alkaline Phosphatase Promotes Mineralization34. Sclerosing Bone Dysplasias35. Melorheostosis36. Fibrodysplasia (Myositis) Ossificans Progressiva37. Craniosynostosis38. Disorders and Mechanisms of Ectopic Calcification39. Thyroid Hormone in Bone and Joint DisordersPART 4: PARATHYROID AND RELATED DISORDER40. Hyperparathyroidism41. Hypoparathyroidism42. Gsα, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune–Albright Syndrome43. Genetic Disorders Caused by Mutations in the PTH/PTHrP Receptor, its Ligands, and Downstream Effector Molecules44. Genetically Determined Disorders of Extracellular Calcium (Cao2+) Sensing and Cao2+ Homeostasis45. Multiple Endocrine Neoplasia SyndromesPART 5: VITAMIN D AND RENAL DISORDERS46. Genetic Disorders of Vitamin D Synthesis and Action47. X-linked hypophosphataemia48. Heritable Renal Phosphate Wasting Disorders49. Genetics of Hypercalciuria and Kidney Stones