Gordon Ginder
Virginia Commonwealth University, VA·Biochemistry
Before birth, red blood cells carry a different version of the oxygen-carrying protein hemoglobin, called fetal hemoglobin. Shortly after birth the gene for it is switched off and the adult version takes over.
- Fields
Biochemistry
Genetics
Medicine & Clinical Research
- Topics
fetal hemoglobin
HbF
gamma-globin
- Grants
- 1 known grant, through Aug 2029
What they work on
- Determine how mutations that break the contact between the GATAD2A CR-2 region and the C-terminal pocket of CHD4, the DNA-repackaging motor of the NuRD complex, affect fetal hemoglobin output in adult-type human red blood cell precursors.
- Test whether disrupting the binding of MBD2's intrinsically disordered region to the histone deacetylase subcomplex of NuRD releases silencing of the gamma-globin gene, using base-specific gene editing in erythroid cells.
- Map in structural detail the two protein-protein interfaces that hold the MBD2-NuRD complex together, to define druggable pockets on CHD4's C-terminal domain and on the deacetylase subcomplex.
- Screen for small molecules and cyclic peptides that bind these pockets tightly and pull the NuRD complex apart, using structure-guided, iterative rounds of design and testing.
- Evaluate promising disruptors for fetal hemoglobin induction and other cellular effects in cultured erythroid systems and in an animal model of primary human red blood cell production.
More about the research
In sickle cell anemia, the adult version is mutated and distorts red blood cells, but patients who keep making fetal hemoglobin have much milder disease. That makes the off switch itself a drug target: if the switch could be released in adult blood-forming cells, patients would make a healthy hemoglobin they already have the gene for. Work in this lab centers on one molecular machine that helps hold the switch off, and on finding chemical compounds that pry it apart.
Why it matters
Gene therapy and stem cell transplantation can help some people with sickle cell anemia, but most patients worldwide will not have access to them soon. A drug that pries apart the MBD2-NuRD complex could reawaken fetal hemoglobin and blunt the disease using a gene patients already carry. Because the same complex supports cancer cell growth, such compounds may also inform treatment of hematologic malignancies and other resistant cancers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
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Build a machine learning model that predicts chronic kidney disease progression in adults with sickle cell disease, using data from a prospective, multicenter study.
The school
Virginia Commonwealth University: 19 labs on PI Pages, $524M a year on research, 438 research doctorates a year.
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