Jaebok Choi, Ph.D.

Assistant Professor
Internal Medicine

Immunology Program
Molecular Cell Biology Program
Cancer Biology Program

  • 314-362-9349

  • 314-273-0153

  • 314-362-1953

  • Southwest Tower, Room 724

  • jchoi25@wustl.edu

  • https://oncology.wustl.edu/people/faculty/Choi/Choi_Bio.html

  • graft-versus-host disease (GvHD), graft-versus-leukemia (GvL), JAK-STAT, immune cell trafficking, transplant immunology, CRISPR/Cas9

  • Understanding T cells and immunoregulatory networks in GvHD and GvL for the treatment of hematopoietic malignancies.

Research Abstract:

The goal of my research program is to identify novel genes whose genetic/pharmacologic blockade may selectively prevent graft-versus-host disease (GvHD) while maintaining or enhancing graft-versus-leukemia (GvL) effects (aka anti-leukemia activities of donor graft). 

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for patients with relapsed/refractory leukemia and marrow failure states such as myelodysplasia and aplastic anemia. The therapeutic benefits of allo-HCT for these patients depend on GvL effects mediated by mature T cells present in the donor graft. Unfortunately, the same donor T cells that mediate the beneficial GvL effect can also cause GvHD. Both GvHD and GvL occur when T cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) and tumors as foreign, thereby initiating an immune reaction in the transplant recipient. Because of a strong association between GvHD and GvL, these two donor T cell-mediated immunologic effects of allo-HCT are difficult to separate. Thus, finding a means to harness the GvL activity of T cells while eliminating their tendency to cause GvHD is a major clinical goal in the allo-HCT field.

To achieve this goal, we have three distinct but closely related projects.
1. Modulation of immune cell trafficking to GvHD target organs vs leukemia cells by targeting interferon gamma receptor and integrins.
2. Role of JAK-STAT signaling in GvHD and tissue restoration.
3. Genome-wide CRISPR/Cas9 screens: The mechanisms by which allogeneic donor T cells differentially modulate GvHD and GvL remain largely unknown. This gap in our mechanistic understanding hinders our ability to specifically prevent/treat GvHD. We hypothesize that the genes we identify as being differentially associated with donor T cells that infiltrate tumors versus GvHD organs will be critical targets for the prevention of GvHD without negatively affecting GvL.

Mentorship and Commitment to Diversity Statement:
A fuller understanding of scientific truth requires diverse approaches and perspectives as each approach and perspective has strengths and limitations. In order to achieve the goals of the research program described above, we employ diverse approaches, which help students and postdocs be equipped as independent scientists. These include hematopoietic stem cell transplantation (mouse-to-mouse and human PBMC-to-mouse), solid organ transplantation (skin and heart), intestinal organoids, unbiased genome-wide CRISPR/Cas9 screens, flow cytometry, and proteomics (mass spectrometry). 

All members of the school regardless of race, color, national origin, sex, age, and disability are welcome to my lab. In order to see something in all its dimensions, I believe, we need more than one perspective. We are committed to learning from each other and striving for inclusive excellence.

I understand that people construct their own way of learning by experiencing things and then reflecting on those experiences. Thus, as a mentor, I pose questions and problems and then guide students and postdocs to help them find their own answers. In addition to diverse approaches and perspectives, communication is a key to success. I have weekly, or daily if needed, meetings one-on-one with students and postdocs to help them create their own knowledge based on what they know and what is newly seen.

Selected Publications:

1. Choi J and Newman AP, “A two-promoter system of gene expression in C. elegans” Developmental Biology 296:537-544, 2006.
2. Choi J, Richards KL, Cinar HN and Newman AP, “N-ethylmaleimide sensitive factor is required for fusion of the C. elegans uterine anchor cell” Developmental Biology 297:87-102, 2006.
3. Sapir A*, Choi J* (*equal contribution), Leikina E, Avinoam O, Valansi C, Chernomordik LV, Newman AP, Podbilewicz B, “AFF-1, a FOS-1-regulated fusogen, mediates fusion of the anchor cell in C. elegans.” Developmental Cell 12:683-698, 2007. PMCID: PMC1975806.
4. Choi J, Ritchey J, Prior J, Holt M, Shannon WD, Deych E, Piwnica-Worms DR, DiPersio JF, “In vivo administration of hypomethylating agents mitigates GvHD without sacrificing GvL” Blood 116:129-139, 2010. PMCID: PMC2904576.
5. Choi J, Ziga ED, Ritchey J, Collins L, Prior J, Cooper ML, Piwnica-Worms DR, DiPersio JF, “IFNγR signaling mediates alloreactive T cell trafficking and GvHD” Blood 120:4093-4103, 2012. PMCID: PMC3496960.
6. Choi J, Cooper ML, Ziga ED, Ritchey J, DiPersio JF, “Effect of Epigallocatechin-3-Gallate on Graft-versus-Host Disease” Cell Transplantation, Epub ahead of print, 2013, 23:1163-1166, 2014. PMCID: PMC4022695.
7. Choi J, Cooper ML, Alahmari B, Ritchey J, Collins L, Holt M, DiPersio JF, “Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect”, PLoS One 9(10):e109799, 2014. PMCID: PMC4188578.
8. Cooper ML, Choi J, Karporva D, Vij K, Ritchey J, Schroeder MA, DiPersio JF, “Azacitidine mitigates GvHD via its differential effects on expansion of T effectors and nTregs in vivo”, Journal of Immunology, 198:3746-3754, 2017. PMCID: PMC5541679.
9. Cooper ML, Choi J, Staser K, Ritchey J, Niswonger J, Rettig M, Wang B, Eissenberg L, Ghobadi A, Gehrs L, Prior J, Achilefu S, Miller C, Fronick C, O’Neal J, Gao F, Weinstock D, Gutierrez A, Eckardt K, Fulton R, DiPersio JF, “An ‘off-the-shelf’ fratricide-resistant and GvHD-resistant CAR-T for the treatment of T cell hematologic malignancies”, Leukemia, 32:1970-1983, 2018. PMCID: PMC6102094.
10. Choi J, Cooper ML, Staser K, Ashami K, Vij K, Wang B, Marsala L, Niswonger J, Ritchey J, Alahmari B, Achilefu S, Tsunoda I, Schroeder MA, DiPersio JF, “Baricitinib-induced blockade of interferon gamma receptor and interleukin-6 receptor for the prevention and treatment of graft-versus-host disease”, Leukemia, 32:2483-2494, 2018. PMCID: PMC6168427.
11. Perry JSA, Russler-Germain EV, Zhou YW, Purtha W, Cooper ML, Choi J, Schroeder MA, Salazar V, Egawa T, Lee BC, Abumrad N, Kim B, Anderson M, DiPersio JF, Hsieh CS, “Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance”, Immunity, 48:923-936, 2018. PMCID: PMC5986080.
12. Alahmari B, Cooper ML, Ziga ED, Ritchey J, DiPersio JF, Choi J, “Selective targeting of histone modification fails to prevent graft versus host disease after hematopoietic cell transplantation”, PLoS One, 13(11):e0207609, 2018. PMCID: PMC6242356.
13. Ashami K, DiPersio JF, Choi J, “Targeting IFNGR/IL6R or downstream JAK1/JAK2 to control GvHD”, Oncotarget, 9:35721-35722, 2018. PMCID: PMC6254668.
14. Alahmari B, Cooper ML, Vij KR, Ritchey J, Ruminski P, Gao F, Choi J* (co-senior author), DiPersio JF*, “Selective Targeting of α4β1 Integrin on Donor T cells Attenuates Murine Graft versus Host Disease”, Leukemia, 34:3100-3104, 2020. PMCID: PMC7483240.
15. Kim S, Santhanam S, Lim S, Choi J, “Targeting Histone Deacetylases to Modulate Graft-Versus-Host Disease and Graft-Versus-Leukemia”, International Journal of Molecular Sciences, 21(12):4281 (1-20), 2020. PMCID: PMC7349873.

Complete List of Published Work in MyBibliography

Last Updated: 4/22/2021 1:23:24 PM

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