Haodi Wu
University of Pittsburgh, PA·Genetics
Cornelia de Lange Syndrome (CdLS) is a genetic disorder that affects many organs. More than 30% of patients have heart defects at birth or weakened heart function in adulthood.
- Fields
Genetics
Physiology
Medicine & Clinical Research
- Topics
Cornelia de Lange Syndrome
CdLS
cohesin
- Grants
- 1 known grant, through Jun 2030
What they work on
- Define how removing NIPBL changes heart-cell function and gene activity, using human iPSC-derived heart muscle cells with a dTAG degradation switch, functional assays and single-cell RNA sequencing.
- Confirm NIPBL's interactions with transcription factors such as GATA4 using advanced imaging, and determine how these interactions shape where these factors bind DNA and how they control gene activity.
- Identify new protein partners of NIPBL in heart cells using co-immunoprecipitation combined with mass spectrometry.
- Test whether the NIPBL–BRD4 complex keeps the genome stable in stressed heart cells, and whether BRD4 inhibition protects stressed heart cells and animal hearts.
More about the research
Most cases are caused by mutations in one copy of the NIPBL gene. NIPBL loads cohesin, a ring-shaped protein complex that holds DNA strands together and folds DNA into loops. How NIPBL acts in human heart cells is unknown, and no treatment specifically addresses the heart problems in CdLS. Progress has been slow for two reasons. Losing both copies of NIPBL is lethal to embryos, and human heart tissue is scarce.
Why it matters
The project could reveal new drug targets for the heart remodeling seen in Cornelia de Lange Syndrome patients who carry NIPBL mutations, and in hearts under other kinds of stress. Testing whether blocking BRD4 helps stressed heart cells and animal hearts may point toward a possible treatment strategy.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Anita Saraf
University of Pittsburgh, PA·Medicine & Clinical Research·Early-career
Determine how inflammatory cytokines, which stay chronically elevated in single-ventricle patients, change calcium handling and contraction in iPSC-derived heart muscle cells carrying hypomorphic NOTCH1 mutations from HLHS patients.
Lei Yang
Indiana University-Purdue University-Indianapolis, IN·Biology
Determine how the human lncRNA MCRL1 and its partner protein β-Catenin switch on heart genes and switch off blood genes during mesoderm specification. The work uses MCRL1-knockout human embryonic stem cells differentiated toward heart cells.
Aditi Gurkar
University of Pittsburgh, PA·Medicine & Clinical Research
Map how oxidative 8-oxoguanine damage at telomeres signals to mitochondria to drive senescence in human iPSC-derived cardiomyocytes and cardiac fibroblasts, using a light-activated chemoptogenetic tool that damages only telomeres.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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