Xuebing Wu
Columbia University, NY·Genetics
Ribosomes are the cell's protein-making machines. They are usually thought to be the same in every tissue.
- Fields
Genetics
Biochemistry
Medicine & Clinical Research
- Topics
ribosome specialization
ribosomal proteins
dilated cardiomyopathy
- Grants
- 2 known grants, through May 2030
What they work on
- Test whether RPL3L ribosomes, which replace the common ribosomal protein RPL3 in muscle, promote protein homeostasis in heart muscle cells, using human cell lines and mice expressing mainly RPL3 or RPL3L.
- Compare how RPL3L and RPL3 ribosomes function, using biochemical, imaging, genomic and computational approaches, to explain why the heart uses a specialized ribosome.
- Determine how diverse patient RPL3L variants, including hotspots G27D and D308N, cause neonatal dilated cardiomyopathy, using isogenic human cells, patient iPSC-derived heart cells and engineered 3D heart tissue.
- Examine the molecular basis of RPL3 compensation seen in mouse models, and develop lead therapeutic candidates and a framework for judging which RPL3L variants cause disease.
More about the research
Heart and skeletal muscle are an exception. There, a protein called RPL3, which sits closest to the ribosome's catalytic center, is largely replaced by a muscle-only version, RPL3L. Mutations in RPL3L cause a severe form of dilated cardiomyopathy, a disease in which the heart enlarges and weakens, leading to fatal heart failure in newborns. Two projects ask why the heart uses a special ribosome and how RPL3L mutations cause disease.
Why it matters
About half of dilated cardiomyopathy cases, and two-thirds in children, have no known cause. Explaining how RPL3L mutations cause fatal newborn heart failure could improve the interpretation of genetic test results for families. It could also point to treatments based on the disease mechanism, such as boosting compensation by RPL3. More broadly, it may reveal how tissue-specialized ribosomes support heart function.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Francesca Briganti
University of California-San Diego, CA·Medicine & Clinical Research·Early-career
Test candidate miRNAs in stem-cell-derived heart muscle cells (iPSC-CMs) carrying DCM variants in PLN, RBM20 or TNNT2, to find the mechanisms by which they improve contraction.
D Foster
Johns Hopkins University, MD·Physiology
Identify the enzymes that convert vitamin A to retinoic acid in adult heart muscle cells, starting from DHRS4, using heart muscle cells and engineered heart tissue grown from human stem cells.
Jidong Fu
Ohio State University, OH·Medicine & Clinical Research
Characterize how Masir, a membrane-associated long noncoding RNA, protects heart muscle cells from ischemic injury by enhancing membrane repair, and assess its safety in mouse models.
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
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