Emery H. Bresnick, PHD

Position title: Professor, Cell and Regenerative Biology

Email: ehbresni@wisc.edu

Phone: 608-265-6446

Organ System/Disease Focus:
Hematology and vascular biology
Aligned Research Focus:
Basic stem cell science; hematopoietic stem and progenitor cells
Emery Bresnick headshot


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Research Description:

We use multidisciplinary approaches to understand stem/progenitor cell function, blood cell development, and vascular biology. Such approaches include genomics, proteomics, chemical genetics, embryonic stem cell differentiation, computational analysis, and traditional methodologies.

In addition to elucidating biological principles, we aim to develop innovative therapeutic strategies based on targeting novel mechanisms.
Projects relevant to stem cell biology/regenerative medicine include:

Mechanisms of hematopoiesis:
We are analyzing the function/regulation of GATA factors that control hematopoietic stem cells (HSCs) and hematopoiesis. Transcriptional profiling and ChIPchip analysis have identified a cohort of novel GATA factor target genes, including genes encoding proteins that bear no obvious similarity to known proteins. Loss-of-function and gain-of-function studies are being conducted in mice, zebrafish, human adult stem/progenitors, and embryonic stem cell systems to discover new modes of controlling stem/progenitor cell function and to devise novel applications towards translational medicine. Defining novel hematopoietic mechanisms has enormous importance, as deviations from physiological programs yield leukemias, lymphomas, myelodysplasia, and additional blood disorders.

Vascular mechanisms and engineering::
We have developed a novel murine model characterized by severe hematopoietic stem/progenitor cell depletion and a severe vascular integrity defect. We are dissecting mechanisms underlying the establishment and maintenance of vascular integrity in normal and disease states. Understanding such mechanisms is essential for developing efficient approaches to promote the vascularization of engineered tissues, a limiting factor in regenerative medicine

Selected References:
  1. Zwifelhofer NM, Cai X, Liao R, Mao B, Conn DJ, Mehta C, Keles S, Xia Y,
    Bresnick EH. GATA factor-regulated solute carrier ensemble reveals a nucleoside
    transporter-dependent differentiation mechanism. PLoS Genet. 2020 Dec
    28;16(12):e1009286. doi: 10.1371/journal.pgen.1009286. PMID: 33370779; PMCID:
  2. Johnson KD, Conn DJ, Shishkova E, Katsumura KR, Liu P, Shen S, Ranheim EA,
    Kraus SG, Wang W, Calvo KR, Hsu AP, Holland SM, Coon JJ, Keles S, Bresnick EH.
    Constructing and deconstructing GATA2-regulated cell fate programs to establish
    developmental trajectories. J Exp Med. 2020 Nov 2;217(11):e20191526. doi:
    10.1084/jem.20191526. PMID: 32736380; PMCID: PMC7596813.
  3. Liao R, Zheng Y, Liu X, Zhang Y, Seim G, Tanimura N, Wilson GM, Hematti P,
    Coon JJ, Fan J, Xu J, Keles S, Bresnick EH. Discovering How Heme Controls Genome
    Function Through Heme-omics. Cell Rep. 2020 Jun 30;31(13):107832. doi:
    10.1016/j.celrep.2020.107832. PMID: 32610133; PMCID: PMC7382780.
  4. Soukup AA, Zheng Y, Mehta C, Wu J, Liu P, Cao M, Hofmann I, Zhou Y, Zhang J,
    Johnson KD, Choi K, Keles S, Bresnick EH. Single-nucleotide human disease
    mutation inactivates a blood-regenerative GATA2 enhancer. J Clin Invest. 2019
    Mar 1;129(3):1180-1192. doi: 10.1172/JCI122694. Epub 2019 Feb 11. PMID:
    30620726; PMCID: PMC6391105.
  5. Katsumura KR, Mehta C, Hewitt KJ, Soukup AA, Fraga de Andrade I, Ranheim EA,
    Johnson KD, Bresnick EH. Human leukemia mutations corrupt but do not abrogate
    GATA-2 function. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10109-E10118.
    doi: 10.1073/pnas.1813015115. Epub 2018 Oct 9. PMID: 30301799; PMCID:
  6. Tanimura N, Liao R, Wilson GM, Dent MR, Cao M, Burstyn JN, Hematti P, Liu X,
    Zhang Y, Zheng Y, Keles S, Xu J, Coon JJ, Bresnick EH. GATA/Heme Multi-omics
    Reveals a Trace Metal-Dependent Cellular Differentiation Mechanism. Dev Cell.
    2018 Sep 10;46(5):581-594.e4. doi: 10.1016/j.devcel.2018.07.022. Epub 2018 Aug
    16. PMID: 30122630; PMCID: PMC6133724.
  7. Mehta C, Johnson KD, Gao X, Ong IM, Katsumura KR, McIver SC, Ranheim EA,
    Bresnick EH. Integrating Enhancer Mechanisms to Establish a Hierarchical Blood
    Development Program. Cell Rep. 2017 Sep 19;20(12):2966-2979. doi:
    10.1016/j.celrep.2017.08.090. PMID: 28930689; PMCID: PMC5618720