Emery H. Bresnick
University of Wisconsin-Madison, WI·Genetics
Every day the bone marrow makes billions of new blood cells from a small pool of stem and progenitor cells, the early cells that divide and mature into specific blood cell types. When the genetic switches that control this process fail, people can develop immune deficiency, anemia or blood cancers.
- Fields
Genetics
Biochemistry
Medicine & Clinical Research
- Topics
hematopoiesis
GATA factors
GATA2 deficiency syndrome
- Grants
- 2 known grants, through Mar 2030
What they work on
- Test whether GATA2 and C/EBPε, a factor that drives granulocyte formation, work together and separately to set up progenitor gene activity, using GATA2 activation of a Cebpe enhancer as the entry point.
- Determine how the disease-causing GATA2 variant T354M keeps part of its activity, testing whether its N-finger DNA-binding region compensates for the damaged C-finger.
- Build a human GATA2 variant curation system that uses activity measurements to give each variant a signature, sorting pathogenic, conditionally pathogenic and benign variants and revealing mechanisms.
- Identify GATA-regulated enhancers that lose open chromatin under inflammation in human red cell progenitors, and test whether inflammation worsens the defects of the GATA2 T354M variant.
- Test how the type, dose and timing of inflammatory signaling decide whether damage to progenitor genomes is reversible, and define which erythropoietin (Epo) target genes are sensitive to inflammation.
- Dissect how inflammation disrupts the BCL11A enhancer, a sickle cell gene-editing target, through GATA factors, lowering BCL11A and raising fetal globin.
More about the research
Both projects ask how GATA factors control blood formation. These proteins turn genes on and off by binding DNA. One project focuses on GATA2 and blood stem and progenitor cells. The other asks how inflammation interferes with GATA factors as red blood cells are made.
Why it matters
This work could help patients with GATA2-deficiency syndrome, MDS, AML, bone marrow failure and anemias that resist erythropoiesis-stimulating drugs. Activity measurements of GATA2 variants may improve clinical genetic diagnosis, and the team already advises physicians on interpreting these variants. Learning how inflammation controls BCL11A and red cell development could inform sickle cell disease therapy and the manufacture of stem cell-derived blood products for transplantation.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Teresa V Bowman
Albert Einstein College of Medicine, NY·Genetics
Test whether DDX41 insufficiency cooperates with age-associated activity of cGAS, an inflammation-triggering DNA sensor, to impair blood stem and progenitor cells in germline ddx41 heterozygous zebrafish that develop MDS-like disease.
Britta Will
Albert Einstein College of Medicine, NY·Biology
Map when chaperone-mediated autophagy (CMA), a selective protein-recycling pathway, is active in precancerous CHIP blood stem cells and leukemic stem cells, using a CMA reporter mouse and lentiviral CMA biosensors in patient cells.
Kyle Hewitt
University of Nebraska Medical Center, NE·Genetics
Define how Samd14, a gene switched on during anemia, supports c-Kit signaling and survival of red blood cell precursors, using primary human and mouse cells.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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