Nicolae David
Northwestern University, IL·Physiology
In chronic kidney disease (CKD), the kidneys slowly lose function. That decline brings problems far beyond the kidney: inflammation, anemia (too few red blood cells), weak bones, iron imbalance, and heart disease that raise the risk of death.
- Fields
Physiology
Medicine & Clinical Research
Biology
- Topics
chronic kidney disease
HNF4α
hepatocyte nuclear factor 4 alpha
- Grants
- 2 known grants, through May 2030
What they work on
- Test whether inflammation suppresses HNF4α, a gene-activating transcription factor, in bone-forming osteoblasts, creating a feed-forward loop that blunts parathyroid hormone (PTH) response, by switching Hnf4α2 on or off in mice with CKD or PTH challenges.
- Determine how osteoblast HNF4α drives red blood cell production through erythropoietin (EPO), using Hnf4α deletion and overexpression, co-cultures with blood precursor cells, and mouse models of iron deficiency anemia, anemia of inflammation, and CKD.
- Test whether kidney HNF4α, regulated upstream by STAT3 signaling, protects against fibrosis and CKD progression, using high-phosphate diets, Col4a3 knockout mice, and Hnf4α overexpression in kidney proximal tubules.
- Establish whether C-terminal FGF23 peptides protect against low blood iron by limiting the iron hormone hepcidin, using genetic mouse models, and test C-terminal FGF23 supplementation against iron deficiency anemia in two CKD mouse models.
- Determine how intact FGF23 and N-terminal FGF23 peptides inhibit red blood cell production and EPO release, and whether red-cell-derived N-terminal FGF23 drives heart thickening in CKD mice and cultured heart muscle cells.
More about the research
Little is known about the molecular signals that tie these problems together, which slows the search for treatments. The lab studies how signals shared between bone, kidney, blood-forming marrow, and heart go wrong in CKD. Its two projects focus on HNF4α, a transcription factor (a protein that switches genes on), and FGF23, a hormone made by bone.
Why it matters
Patients with chronic kidney disease often suffer bone fragility, anemia, iron problems, and heart enlargement, all of which raise their risk of death. By testing how HNF4α loss and FGF23 fragments drive these complications, the work could point to new therapeutic targets. Examples include restoring HNF4α activity or supplementing C-terminal FGF23 to protect bone, blood production, kidney function, and the heart in CKD.
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.
Emery H. Bresnick
University of Wisconsin-Madison, WI·Genetics
Test whether GATA2 and C/EBPε, a factor that drives granulocyte formation, work together and separately to set up progenitor gene activity, using GATA2 activation of a Cebpe enhancer as the entry point.
Clintoria Williams
Wright State University, OH·Physiology
Test whether zinc supplementation in early CKD restores zinc balance, limits kidney sodium reabsorption, lowers blood pressure and slows disease in calcineurin inhibitor-treated mice and Akita diabetic kidney disease mice.
The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
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