Jaebok Choi
Washington University in St Louis, MO·Microbiology & Immunology
For many patients with blood cancers or failing bone marrow, the only cure is a transplant of blood-forming cells from a donor. This procedure is called allogeneic hematopoietic cell transplantation (allo-HCT).
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Genetics
- Topics
graft-versus-host disease
GvHD
graft-versus-leukemia
- Grants
- 1 known grant, through Apr 2031
What they work on
- Test whether drug blockade of VLDLR, a receptor on T cells, prevents graft-versus-host disease while preserving the graft-versus-leukemia effect, in two independent mouse models of allogeneic hematopoietic cell transplantation.
- Define the cellular mechanisms by which genetic or drug blockade of VLDLR separates GvHD from GvL, including changes in regulatory T cells and in CD4 versus CD8 T cell responses.
- Test whether blocking VLDLR prevents GvHD and leukemia relapse by raising Klrc1, the gene for the immune-modulating receptor NKG2A, specifically in CD4 T cells, building on RNA-seq of VLDLR knockout T cells.
More about the research
Much of its benefit comes from donor T cells, immune cells that attack remaining leukemia cells in the graft-versus-leukemia (GvL) effect. The same T cells can also attack the patient's healthy tissues, causing graft-versus-host disease (GvHD), which affects about 30–50% of recipients. Treatments that suppress GvHD often weaken GvL too, and deaths from leukemia relapse after transplant have risen over the past 40 years. How donor T cells drive these two effects differently remains unknown.
Why it matters
Patients with blood cancers and marrow failure who need a donor transplant could benefit if GvHD can be prevented without losing the transplant's anti-leukemia effect. Mouse and human VLDLR are 97% identical, so the team sees VLDLR blockade as a candidate for a first-in-human trial. It may offer an inexpensive, safe way to overcome donor-matching barriers, including for patients without suitable donors.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Xuefang Cao
University of Maryland, Baltimore, MD·Microbiology & Immunology
Determine whether blood-forming stem and progenitor cells use the receptor CD27 to directly suppress donor T cells, using transplants into Rag1 knockout mice that lack CD27 and NK cells, in vivo and in vitro.
Benjamin Vincent
University of North Carolina at Chapel Hill, NC·Microbiology & Immunology
Evaluate how large structural DNA variants contribute immunogenic minor histocompatibility antigens that donor T cells target after HLA-matched stem cell transplantation for AML.
John Wagner
University of Minnesota, MN·Medicine & Clinical Research
Establish the safety and maximum tolerated dose of donor CAR19 regulatory T cells, given with and without IL-2, in patients with relapsed or refractory CD19+ acute lymphocytic leukemia, measuring cell persistence and tumor killing.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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