Demetrios Braddock
Yale University, CT·Medicine & Clinical Research
Some people's bodies deposit mineral in the wrong places: they have weak, low-density bones while calcium deposits build up in kidneys, tendons and blood vessels. This "paradoxical mineralization" occurs in inherited disorders caused by faulty ENPP1, an enzyme.
- Fields
Medicine & Clinical Research
Physiology
Pharmacology
- Topics
pyrophosphate
PPi
bone mass
- Grants
- 1 known grant, through Apr 2027
What they work on
- Identify the signaling pathways by which ENPP1, the only human enzyme that makes the mineral inhibitor pyrophosphate, regulates bone mass, including pathways independent of its enzyme activity.
- Separate ENPP1's catalysis-dependent and catalysis-independent gene and protein signaling, using animal models that uncouple ENPP1 protein signaling from its enzyme activity.
- Measure how activating each ENPP1 function with engineered biologics affects bone fragility, microarchitecture, growth and mineralization biomarkers in living animals.
More about the research
It also appears in aging and in chronic kidney disease mineral and bone disorder (CKD-MBD), where fracture risk and death rates have barely improved in 20 years. Understanding how ENPP1 controls bone mass could explain this paradox and guide better treatments.
Why it matters
Patients with inherited ENPP1 deficiency, such as GACI, ARHR2 and early-onset osteoporosis, and people with chronic kidney disease mineral and bone disorder face fractures and high mortality with poor current treatment options. Identifying how ENPP1 controls bone mass could explain an unrecognized form of hereditary osteoporosis and may inform better therapies for these paradoxical mineralization conditions.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Erica Clinkenbeard
Indiana University-Purdue University-Indianapolis, IN·Physiology
Test whether low iron weakens bone formation in CKD by reducing spermine, by giving spermine during iron deficiency to cultured bone-building cells (osteoblasts) and to mice with adenine diet-induced kidney failure.
Yujun Cai
Yale University, CT·Pharmacology
Investigate how PDE10A drives vascular smooth muscle cells exposed to high phosphate to turn into bone-like cells and calcify, using PDE10A knockdown and inhibition in cultured cells and PDE10A-deficient animals.
John Fowlkes
University of Kentucky, KY·Physiology
Determine how deficiencies of insulin and insulin-like growth factor 1 (IGF-1) each contribute to diabetic bone disease at the tissue, cellular and molecular levels in models of type 1 diabetes.
The school
Yale University: 73 labs on PI Pages, $1.5B a year on research, 438 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.