Fernando Fierro
University of California-Davis, CA·Physiology
Polyamines are small, positively charged molecules found in nearly all cells of plants, animals and fungi. They stick to negatively charged structures such as DNA packaging, cell membranes and ion channels.
- Fields
Physiology
Genetics
Medicine & Clinical Research
- Topics
Snyder-Robinson Syndrome
spermine synthase
polyamines
- Grants
- 1 known grant, through Jun 2031
What they work on
- Uncover how spermine synthase (SMS) deficiency impairs bone mineralization, testing whether excess spermidine blocks hypusination, the chemical activation of the protein eIF5A, and disrupts mitochondrial release of calcium phosphate.
- Generate mice in which Sms can be switched off body-wide (Ubc-creERT2) to mimic Snyder-Robinson Syndrome, and establish a causal link between SMS loss, mitochondrial dysfunction and impaired bone formation.
- Determine whether the skeletal defects arise within the skeleton itself by deleting Sms only in skeletal precursor cells, using Prrx1-creERT2 mice.
- Test whether bone-building osteoanabolic drugs or a compound that adjusts polyamine levels improve bone health in SMS-deficient mice.
More about the research
Their role in bone is largely unexplored. Snyder-Robinson Syndrome (SRS) offers a window into it. SRS is a rare inherited disorder carried on the X chromosome that causes intellectual disability and severe skeletal problems. These include a curved spine (scoliosis and kyphoscoliosis) and fragile bones (osteoporosis), so children often break bones even without injury. SRS is caused by loss-of-function mutations in SMS (spermine synthase), the enzyme that turns the polyamine spermidine into spermine. Patients therefore have too much spermidine compared with spermine, but how this imbalance damages bone is unknown.
Why it matters
Children with Snyder-Robinson Syndrome suffer severe skeletal defects and frequent fractures, and the cause is not understood. Pinpointing how spermine synthase loss disrupts mitochondria and bone mineral formation could reveal treatment targets. Testing bone-building drugs and a polyamine-adjusting compound in mice could point toward ways to improve bone health in these patients and clarify how polyamines affect bone more broadly.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Andre Bachmann
Michigan State University, MI·Pharmacology
Characterize and drug-treat mouse models that mimic ODC1 gain-of-function mutations in Bachmann-Bupp Syndrome to find the molecular mechanisms behind the patient phenotype.
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.
Archana Sanjay
University of Connecticut, CT·Biology
Test whether Rspo2 and Rspo3 are needed in mesenchymal progenitors for fracture healing, by deleting these genes at the time of fracture in mice and assessing repair with microCT, histology and mechanical testing.
The school
University of California-Davis: 49 labs on PI Pages, $1.0B a year on research, 647 research doctorates a year.
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