Dr. Harald Jueppner
Harald Jueppner, MD, is the Chief of Pediatric Nephrology at the Massachusetts General Hospital and a Professor of Pediatrics at Harvard Medical School.
He has had a long-standing interest in the regulation of calcium and phosphate homeostasis as well as the mechanisms contributing to bone growth and turnover. He and his colleagues were the first to isolate cDNAs encoding the PTH/PTHrP receptor (PTHR1), which allowed the search for human disorders caused by mutations in this gene. Initially it was thought that such mutations are the cause of pseudohypoparathyroidism types Ib (PHP1B); however, his group excluded such mutations, subsequently mapped the genetic locus for the autosomal dominant form of PHP1B (AD-PHP1B) to the GNAS complex locus on chromosome 20q13, and eventually showed that deletions in GNAS or STX16 are disease-causing.
Instead, Dr. Jueppner’s group identified several different, activating mutations in Jansen’s metaphyseal chondrodysplasia (JMC), which is characterized by severe and crippling bone deformities, short-limbed dwarfism, and hypercalcemia. Expression of the PTHR1 mutant under the control of the type II collagen promoter (Col2-H223R-PTHR1) in mice resulted in a significant delay in chondrocyte differentiation, while expression of one of the mutant receptors under the control of the collagen type I promoter (Col1-H223R-PTHR1) resulted in massive new bone formation.
Together with Dr. Gardella, Dr. Jueppner now explores in vitro and in vivo the role of inverse agonists at the PTHR1 for the treatment of growth plate and bone abnormalities observed in the currently available transgenic mouse JMC models.
Dr. William G. Mackenzie
William Mackenzie, M.D. is Chairman of the Department of Orthopaedic Surgery, is the holder of the Shands/MacEwen Endowed Chair at the Nemours, Alfred I. duPont Hospital for Children and is a Professor of Orthopaedic Surgery at Jefferson Medical College. Dr. Mackenzie is Chairman of the Medical Advisory Board for Little People of America and Medical Director of the Dwarf Athletic Association of America. He is the past President of the Limb Lengthening and Reconstruction Society. Dr. Mackenzie is certified by the American Board of Orthopaedic Surgery and is a Fellow of the American College of Surgeons and the Royal College of Physicians and Surgeons of Canada.
His clinical interests include skeletal dysplasia, limb length discrepancy, limb alignment and muscle diseases. With his expertise in these areas he is frequently invited to teach and lecture locally, nationally and internationally.
Dr. Mackenzie earned his medical degree and completed his residency at the University of British Columbia. He completed his internship at McGill University and completed his fellowship in pediatric orthopaedics at the Nemours/Alfred I. duPont Hospital for Children.
Dr. Mackenzie is an active member in numerous societies and served on the Board of Directors of the Pediatric Orthopaedic Society of North America. His distinctions include being named “Best Doctors in America” and “Guide to America’s Top Surgeons” since 2002. He has over 100 publications in peer reviewed journals and has written 17 book chapters.
Dr. Thomas J. Gardella
Massachusetts General Hospital & Harvard Medical School
Thomas Gardella, Ph.D. is an Assistant Professor in Medicine and Biochemistry at the Massachusetts General Hospital and Harvard Medical School. He conducts laboratory research within the MGH Endocrine Unit, of which he has been a member since 1988.
Dr. Gardella’s research concerns the basic mechanisms by which peptide hormones interact with their cell-surface receptors, and specifically focuses on the parathyroid hormone (PTH) receptor. The PTH receptor is a G protein-coupled receptor that acts as a critical regulator of intracellular signaling processes involved in bone growth and blood calcium ion homeostasis. Alterations that perturb the PTH receptor cell signaling system are associated with a number of diseases of bone and mineral ion physiology. By dissecting the molecular mechanisms by which the PTH receptor functions, Dr. Gardella hopes to reveal clues that may help in the development of new therapies for such diseases, including Jansen’s chondrodysplasia, hypoparathyroidism and osteoporosis.
Dr. Isidro B. Salusky
Dr. Salusky is a Distinguished Professor of Pediatrics and Chief, Division Pediatric Nephrology at the David Geffen School of Medicine at UCLA, Los Angeles, California. As a clinical-translational research scientist, he has focused his research efforts on the abnormalities of bone and mineral metabolism that are associated with chronic kidney disease (CKD) in children. Over the years, he has aimed to advance our understanding of the mechanisms of disordered mineral metabolism in patients with CKD, including the role of parathyroid hormone, vitamin D, and more recently fibroblast growth factor 23 (FGF23). Through continuous NIH funding, his research group has described the features of bone diseases across the stages of CKD, and after renal transplantation. In addition, they have demonstrated that the recommended doses of aluminum-containing binders were associated plasma and tissue aluminum accumulation. Furthermore, they have defined the effects of therapy with active vitamin D sterols and phosphate binders on the skeletal lesion of secondary hyperparathyroidism and demonstrated control of the skeletal lesions of secondary hyperparathyroidism, but persistence of a mineralization defect. His group has also provided significant groundwork for elucidating the relationship between abnormalities of bone and mineral metabolism and vascular calcifications in children and young adults treated with dialysis.
His current efforts are focused on studying the role of FGF23 in the pathogenesis of CKD-Mineral and Bone Disorder, with the aim of understanding the relationship between bone and FGF23 across the spectrum of CKD. Dr. Salusky also runs a clinic devoted only to abnormalities of bone and mineral metabolism beyond chronic kidney disease in children.
Dr. Salusky is also extremely involved and committed to the training of the next generation of physician-scientists and specifically in pediatric nephrology, he is the Principal Investigator of the NIH/NIDDK T32DK104687 that support training of post-doctoral MDs and/or PhDs in different aspects related to the consequences of chronic kidney disease on the growing child.
Dr. Michael B. Bober
Dr. Michael B. Bober is the Director of the Skeletal Dysplasia Program at the Alfred I. duPont Hospital for Children in Wilmington, DE and a Professor of Pediatrics at Thomas Jefferson University’s Stanley Kimmel Medical College. He completed a combined M.D./Ph.D. program in Biomedical Engineering at Tulane University. His dissertation research focused on the genetic response of bone to mechanical stimulation. He then went on to complete a Pediatrics Residency at Tulane University and a Medical Genetics Residency and Fellowship at Johns Hopkins University. He is a board certified in Pediatrics, Clinical Genetics and Molecular Genetics. His clinical practice is focused on the diagnosis and management of children with skeletal dysplasia.
Colleen P. Ditro, NP
Nemours/Alfred I. duPont Hospital for Children
1600 Rockland Road
Wilmington, DE
Barbara Gales, RN, BSN
Research Coordinator Pediatric Nephrology
Program Coordinator, UCLA Pediatric Bone Disorders Program
UCLA Mattel Children’s Hospital
The UCLA Pediatric Bone Disorder Program offers a diverse multidisciplinary approach to evaluation, identifying, and treatment of abnormalities of bone and mineral metabolism in children. As program coordinator, Barbara, ensures that the program provides a complete service for both the pediatric patient and their families. Services provided through the Bone Clinic include, diagnostic bone biopsies, bisphosphate therapies, biochemical review, and imaging studies. An integral component of this program includes patient education; perpetuating the belief that building and maintaining bone health is through knowledge.
As part of Dr. Isidro Salusky’s research team, Barbara is the nurse coordinator of his NIH research projects, investigating the abnormalities of bone and mineral metabolism that are associated with chronic kidney disease (CKD) in children.