Clemens Bergwitz, MD
Associate Professor of Medicine (Endocrinology)Cards
About
Research
Overview
Genetic causes of hypophosphatemia
In 2006 we identified the genetic defect underlying the childhood disorder Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). HHRH is caused by mutations in NaPi-IIc, a renal sodium-phosphate co-transporter, which is important to conserve phosphate in the kidney and when lost leads to hypophosphatemia and rickets. Our research goal is now to study the role of NaPi-IIc in human phosphate homeostasis and to understand the phenotypic variability of patients suffering from HHRH. For this purpose we are currently using mammalian and Xenopus oocyte expression systems to study the functional properties of the identified human NaPi-IIc mutations in vitro. Plan for the near future is to establish mouse models to study the role of NaPi-IIc in the development of renal stones in vivo. We also established international collaborations to look for NaPi-IIc mutations in new patients suffering from HHRH both to establish their molecular diagnosis and to carefully study their symptoms to see whether only some or all patients are at risk for developing kidney stones. In addition to HHRH I serve as the principal investigator on clinical trials for serveral other genetic skeletal disorders, including X-linked hypophosphatemia, osteogenesis imperfecta and hypophosphatasia.
Metabolic and homeostatic effects of phosphate
A more recent research interest is in trying to understand how human and other metazoan cells sense inorganic phosphate to explain the effects of phosphate on cell metabolism (“metabolic” sensing), how phosphate feeds back to regulate the above hormonal systems (“homeostatic” sensing) and whether the “metabolic” and the “homeostatic” sensor use the same or different signal transduction cascades.
For this purpose we have performed a genome-wide Drosophila RNAi knockdown in collaboration with Stephanie Mohr, Liz Perkins and Norbert Perrimon, Harvard Medical School using phosphate-induced activation of MAPK (in vitro). The identified 103 genes, including 84 phosphate-specific genes are currently evaluated in life flies with assays for dietary phosphate toxicity, hemolymph phosphate and life span. Our goal in the next few years will be to identify mammalian systems suitable to study phosphate sensing, while further exploring Drosophila melanogaster as model organism. Relevant readouts for humans will be the homeostatic regulation of synthesis and secretion of PTH, 1,25-D, FGF23 by phosphate and it’s metabolic effects on life-span in genetic disorders such as familial hyperphosphatemic tumoral calcinosis (FHTC) and in chronic kidney disease.
Medical Subject Headings (MeSH)
Academic Achievements & Community Involvement
Clinical Care
Overview
Clemens W.H. Bergwitz, MD, is an endocrinologist at Yale Medicine who sees patients with hypophosphatemic disorders, osteoporosis, primary hyperparathyroidism, hyperthyroidism, thyroid nodules, and hypogonadism, as well as adrenal and general endocrine disorders.
Dr. Bergwitz’s characterizes the endocrine system as the human body’s own data messaging system. “It sends information to regulate some of our body’s most critical functions,” he says. In addition to treating patients, Dr. Bergwitz conducts research on many of these conditions, and his lab has worked on projects that test various therapies for hereditary endocrine disorders. “I am really a physician-scientist. My patients inspire my research, which eventually leads back to the bedside,” he says.
Dr. Bergwitz believes that patients should be the expert of their own illness. He strives to explain conditions and treatments in plain language so that patients not only understand their disorder, but also the biological mechanisms behind it. “I’m interested in providing my patients with the information they need to not only understand their condition, but to empower them to take good care of themselves,” he says.
Clinical Specialties
Fact Sheets
Hyperparathyroidism
Learn More on Yale MedicineOsteoporosis
Learn More on Yale MedicineLow Bone Density
Learn More on Yale MedicineVitamin D Deficiency
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Board Certifications
Certified Clinical Densitometrist
- Certification Organization
- The International Society for Clinical Densitometry
- Original Certification Date
- 2015
Endocrinology Diabetes & Metabolism
- Certification Organization
- AB of Internal Medicine
- Latest Certification Date
- 2016
- Original Certification Date
- 2005
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Latest Certification Date
- 2016
- Original Certification Date
- 2004
Yale Medicine News
News
News
- April 14, 2022
Yale Bone Center Celebrates 35 Years of Consistent Progress
- January 10, 2022
Clinical Study Investigates Impact of Phosphate Metabolism on Healthy Aging
- September 20, 2021
Yale Endocrinology & Metabolism Publications
- June 25, 2019
MFS2 Regulation Controls Phosphate Excretion, Renal Stone Formation, Study Finds