Yoseph Barash
University of Pennsylvania, PA·Genetics
Some inherited diseases arise not because a protein is broken but because cells make too little of it from the one working copy of a gene. One way to raise that output lies in upstream open reading frames (uORFs).
- Fields
Genetics
Computer Science
Biochemistry
- Topics
uORF
upstream open reading frame
5' UTR
- Grants
- 1 known grant, through May 2027
What they work on
- Identify functional uORFs, short regulatory reading frames in the 5' untranslated regions of genes, and rank them for testing by combining gnomAD, the Penn Medicine BioBank and the UK Biobank.
- Build a public, user-friendly web tool and database of human uORFs from the computational pipeline.
- Validate high-priority uORF targets with luciferase reporter assays and feed the results back to improve the ranking pipeline, with an emphasis on a pathway linked to pulmonary arterial hypertension.
More about the research
These are short protein-coding stretches in the 5' untranslated region (UTR), the leading part of a messenger RNA that sits before the main gene. uORFs can hold back how much protein the main gene produces. The team reports having found a widely applicable, targeted way to increase protein output from a single good gene copy. This joint, two-lab project aims to find which human uORFs truly regulate protein levels and could be targeted as treatments.
Why it matters
Many hereditary diseases occur when one gene copy makes too little protein. Identifying uORFs that limit protein output could reveal ways to boost protein from the healthy copy. Pulmonary arterial hypertension is one emphasis. A public uORF database could also help other researchers find treatment targets for further inherited disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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University of Michigan, MI·Biochemistry·Early-career
Directly measure ribosome recruitment on thousands of 5′-UTR sequences, the leader regions of mRNAs, that are used differently in cancer cells, to identify functional RNA elements.
Peng Yao
University of Rochester, NY·Physiology
Determine how FAM210A regulates mitochondrial calcium balance, testing whether it acts as a regulator of the calcium/proton exchanger LETM1 in cardiomyocytes, in vitro and in vivo.
Harriet Dashnow
University of Colorado Denver/Anschutz Medical Campus, CO·Genetics·Early-career
Build a public, population-scale catalog of short tandem repeat variation grouped by ancestry, emphasizing diverse and underserved populations, so disease-causing repeat expansions can be prioritized.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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