Emery Bresnick, PhD
Position title: Gary Felsenfeld Professor of Cell and Regenerative Biology; Lowell and Gwendolyn Smythe Endowed Professor; Director, Wisconsin Blood Cancer Research Institute
Website: WI Blood Cancer Research Institute
1111 Highland Ave
Hematopoiesis, Blood Cancer Mechanisms and Genome/Epigenome Function
The Bresnick group conducts basic and translational research on genomics/epigenomics, hematopoiesis, myeloid/erythroid cell biology and pharmacology. We discovered GATA2 enhancers that are essential for hematopoiesis and embryonic development, and their disruption causes human diseases. Our studies unveiled paradigms to explain hematopoietic stem cell generation, progenitor fate decisions and erythrocyte development. Germline mutation of the +9.5 enhancer (or coding mutations) cause GATA2-deficiency syndrome, which involves immunodeficiency, bone marrow failure and predisposition to develop myelodysplastic syndromes and acute myeloid leukemia. An additional enhancer discovered by the Bresnick group (-77) is expropriated by the protooncogene EVI1, thus defining a novel leukemia mechanism. Clinical centers screen for genetic variation in these enhancers to diagnose the molecular basis of blood diseases and direct clinical decisions. We are expanding the mechanistic depth of this discovery science and conducting multi-disciplinary studies of pre-malignant states. We identified GATA2-instigated networks that control hematopoiesis and are deciphering the importance of components of these networks, including many genes/proteins representing potential targets to enhance the diagnosis, treatment and prevention of bone marrow failure, leukemia and clonal hematopoiesis of indeterminate potential (CH). CH afflicts large numbers of people, especially the elderly, and is associated with blood cancers and cardiovascular disease. The GATA2 work guided genomic studies that identified a large enhancer cohort predicted to serve critical roles. One of these enhancers controls expression of a new regulator of c-Kit receptor tyrosine kinase signaling, Samd14, which confers survival in anemia. Studies are testing whether dysregulation of these components in families with a history of hematologic disease, yet lack mutations in established hematopoietic regulators, corrupts GATA2 genetic networks as a pathogenic mechanism. Screening systems are being developed to rescue network defects to overcome differentiation blockades. We use multi-omic (quantitative proteomic, transcriptomic, metabolomic and lipidomic) approaches in cell populations and single cells to understand stem/progenitor cells as well as myeloid and erythroid cell biology. These studies have important fundamental and translational implications, including how the innate immune system and epigenetic mechanisms operate in normal and disease contexts. Of particular note are discoveries of epigenetic mechanisms controlling differentiation, small molecule determinants of genome/epigenome function, RNA exosome complex requirement to balance proliferation and differentiation and metal-dependent mechanisms that control survival and differentiation.
Honors & Awards
- 2023 – University of Kansas, Ivan Damjanov Lecture in Stem Cell Research
- 2022 – Mayo Clinic-Rochester Biochemistry and Mol Biology, Szent-Gyorgyi Named Lectureship
- 2021 – UW Medical Foundation Professorship
- 2020 – Gwendolyn and Lowell Smythe Endowed Professorship
- 2020 – Wisconsin Alumni Research Foundation Professorship (Gary Felsenfeld Professor of Cell and Regenerative Biology)
- 2019 – Direct American Society of Hematology K2R mentoring program at annual meeting
- 2019 – Co-Vice Chair (2023) and Co-Chair (2025) of Red Cell Gordon Research Conference
- 2013 – Kellett Mid-Career Faculty Scholar Award, University of Wisconsin Graduate School
- 2011 – NIH R37 MERIT award
- 2007 – Distinguished Alumnus Award, University of Michigan, Department of Pharmacology
- 2002 – Romnes Faculty Scholar Award, University of Wisconsin Graduate School
- 2000 – Vilas Associate Award, University of Wisconsin Graduate School
- Jung MM, Shen S, Botten GA, Olender T, Katsumura KR, Johnson KD, Soukup AA, Liu P, Zhang Q, Jensvold ZD, Lewis PW, Beagrie RA, Low JK, Yang L, Mackay JP, Godley LA, Brand M, Xu J, Keles S, Bresnick EH. (2023) Pathogenic human variant that dislocates GATA2 zinc fingers disrupts hematopoietic gene expression and signaling networks. J. Clin. Invest. 133(7):e162685.
- Tran, V. L., Liu, P., Katsumura, K. R., Kim, E., Schoff, B. M., Johnson, K. D., & Bresnick, E. H. (2023) Restricting genomic actions of innate immune mediators on fetal hematopoietic progenitor cells. iScience, 26(4), 106297.
- Kim, J. A., Shen, S., Matson, D. R., Lovrien, L. N., Smith-Simmer, K. J., Keles, S., Churpek, J. E., & Bresnick, E. H. (2023) Discriminating activities of DEAD-Box Helicase 41 from myeloid malignancy-associated germline variants by genetic rescue. Leukemia, 37(1), 235–239.
- Soukup, A. A., Matson, D. R., Liu, P., Johnson, K. D., & Bresnick, E. H. (2021) Conditionally pathogenic genetic variants of a hematopoietic disease-suppressing enhancer. Science advances, 7(50), eabk3521.
- Mehta, C., Fraga de Andrade, I., Matson, D. R., Dewey, C. N., & Bresnick, E. H. (2021) RNA-regulatory exosome complex confers cellular survival to promote erythropoiesis. Nucleic acids research, 49(16), 9007–9025.
- Johnson, K. D., Conn, D. J., Shishkova, E., Katsumura, K. R., Liu, P., Shen, S., Ranheim, E. A., Kraus, S. G., Wang, W., Calvo, K. R., Hsu, A. P., Holland, S. M., Coon, J. J., Keles, S., & Bresnick, E. H. (2020) Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories. J. Exp. Med. 217(11), e20191526.
- Liao, R., Zheng, Y., Liu, X., Zhang, Y., Seim, G., Tanimura, N., Wilson, G. M., Hematti, P., Coon, J. J., Fan, J., Xu, J., Keles, S., & Bresnick, E. H. (2020) Discovering How Heme Controls Genome Function Through Heme-omics. Cell Rep. 31(13), 107832.
- Cavalcante de Andrade Silva, M., Katsumura, K. R., Mehta, C., Velloso, E. D. R. P., Bresnick, E. H., & Godley, L. A. (2021) Breaking the spatial constraint between neighboring zinc fingers: a new germline mutation in GATA2 deficiency syndrome. Leukemia, 35(1), 264–268.
- Churpek, J. E., & Bresnick, E. H. (2019) Transcription factor mutations as a cause of familial myeloid neoplasms. J. Clin. Invest. 129(2), 476–488.
- Soukup, A. A., Zheng, Y., Mehta, C., Wu, J., Liu, P., Cao, M., Hofmann, I., Zhou, Y., Zhang, J., Johnson, K. D., Choi, K., Keles, S., & Bresnick, E. H. (2019) Single-nucleotide human disease mutation inactivates a blood-regenerative GATA2 enhancer. J. Clin. Invest. 129(3), 1180–1192.
- Katsumura, K. R., Mehta, C., Hewitt, K. J., Soukup, A. A., Fraga de Andrade, I., Ranheim, E. A., Johnson, K. D., & Bresnick, E. H. (2018) Human leukemia mutations corrupt but do not abrogate GATA-2 function. Natl. Acad. Sci. USA. 115(43), E10109–E10118.
- Tanimura, N., Liao, R., Wilson, G. M., Dent, M. R., Cao, M., Burstyn, J. N., Hematti, P., Liu, X., Zhang, Y., Zheng, Y., Keles, S., Xu, J., Coon, J. J., & Bresnick, E. H. (2018) GATA/Heme Multi-omics Reveals a Trace Metal-Dependent Cellular Differentiation Mechanism. Dev. Cell. 46(5), 581–594.e4.
- Mehta, C., Johnson, K. D., Gao, X., Ong, I. M., Katsumura, K. R., McIver, S. C., Ranheim, E. A., & Bresnick, E. H. (2017) Integrating Enhancer Mechanisms to Establish a Hierarchical Blood Development Program. Cell Rep. 20(12), 2966–2979.
- Hewitt, K. J., Katsumura, K. R., Matson, D. R., Devadas, P., Tanimura, N., Hebert, A. S., Coon, J. J., Kim, J. S., Dewey, C. N., Keles, S., Hao, S., Paulson, R. F., & Bresnick, E. H. (2017) GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia. Dev. Cell. 42(3), 213–225.e4.
- Johnson, K. D., Kong, G., Gao, X., Chang, Y. I., Hewitt, K. J., Sanalkumar, R., Prathibha, R., Ranheim, E. A., Dewey, C. N., Zhang, J., & Bresnick, E. H. (2015) Cis-regulatory mechanisms governing stem and progenitor cell transitions. Sci Advances. 1(8), e1500503.
- Hewitt, K. J., Kim, D. H., Devadas, P., Prathibha, R., Zuo, C., Sanalkumar, R., Johnson, K. D., Kang, Y. A., Kim, J. S., Dewey, C. N., Keles, S., & Bresnick, E. H. (2015) Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome. Mol. Cell. 59(1), 62–74.