Kathryn Oliver
Emory University, GA·Genetics
Cystic fibrosis affects roughly 100,000 people worldwide and comes from mutations in a single gene, CFTR, which makes a channel that moves chloride ions across cell surfaces to keep mucus thin. More than 2,100 disease-causing CFTR variants are known.
- Fields
Genetics
Biochemistry
Pharmacology
- Topics
cystic fibrosis
premature termination codon
nonsense mutation
- Grants
- 1 known grant, through Nov 2029
What they work on
- Determine how inhibiting specific ribosomal proteins, including RPL12 (uL11) and RPL8 (uL2), affects the biogenesis of CFTR premature termination codon variants such as W1282X and G542X.
- Define whether silencing ribosomal proteins rescues CFTR nonsense alleles by altering translation kinetics, ribosome fidelity, or messenger RNA surveillance pathways such as nonsense mediated decay.
- Test outcomes of ribosomal protein disruption in humanized cystic fibrosis mice carrying human CFTR variants, including whether partial repression is tolerated in vivo.
- Identify additional ribosomal proteins beyond RPL12 and RPL8 that mediate rescue of CFTR nonsense variants, establishing translational control as a checkpoint in their processing.
More about the research
About 13% of patients carry a premature termination codon (PTC) — a mutation that tells the ribosome, the cell's protein-building machine, to stop early. These patients make little or no protein, their CFTR messenger RNA is destroyed by a quality-control system called nonsense mediated decay, their disease tends to be more severe, and approved CFTR drugs do not help them. This project pursues a different angle: rather than fixing the mutation, change how fast and how accurately the ribosome reads the message.
Why it matters
People with cystic fibrosis who carry premature stop mutations have more severe disease and cannot benefit from approved CFTR therapies. Showing that partially reducing specific ribosomal proteins restores production of these faulty channels, and explaining how, could open a therapeutic route for this underserved group. Because premature termination codons cause more than 2,400 severe genetic disorders, the same strategy could eventually be tested in other inherited diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
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The school
Emory University: 70 labs on PI Pages, $1.2B a year on research, 286 research doctorates a year.
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