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Emery
H. Bresnick, Ph.D.
Affiliate
Professor of Medicine |
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Trainer
in the Following Programs:
- Molecular
and Cellular Pharmacology
- Cell and
Molecular Biology
- Biomolecular
Chemistry
- Cancer
Biology
- Biotechnology
- Pathology
and Laboratory Medicine
- Hematology
- MD/PhD
- Translational
Cardiovascular Science
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Awards and Honors:
- 2005 - Chair,
NIH Erythrocyte and Leukocyte Biology Study Section
- 2005 - Member
of Molecular and Cellular Biology Editorial Board
- 2002 - Associate
Editor, Journal of Cellular Physiology
- 2002 - Member
of Nucleic Acids Research Editorial Board
- 2002 - Member
of Journal of Biological Chemistry Editorial Board
- 2002 - Romnes
Faculty Scholar - See Article
- 2001 - NIH Hematology
II Study Section Member
- 2000 - Vilas
Associate Award
- 1997 - National
Institutes of Health K02 Career Development Award
- 1997 - Leukemia
Society of America Scholar Award
- 1996 - Shaw Scientist
Award
- 1994 - Pharmaceutical
Manufacturers of America Foundation Faculty Development Award
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Bresnick
Lab Web Site
Research Description:
Stem Cell Biology, Molecular Hematology, and Vascular Biology: From Fundamental Mechanisms to Translational Medicine
We use multidisciplinary, integrative approaches to understand important biological processes, including stem/progenitor cell function, blood cell development (hematopoiesis), and vascular biology. Such approaches include genomics, proteomics, chemical genetics, and computational analysis, as well as traditional molecular, cellular, and biochemical methodologies. In addition to elucidating biological principles, we aim to develop innovative therapeutic strategies based on targeting novel mechanisms.
A major project is to dissect mechanisms that regulate hematopoietic stem cell differentiation into specific progenitor cells, which in turn, form the specific blood cell types. Defining such mechanisms has enormous importance, as deviations from hematopoietic programs lead to the development of leukemias, lymphomas, myelodysplasias and additional blood disorders. Furthermore, while hematopoietic stem cells are routinely transplanted to treat diverse diseases, their therapeutically desirable long-term repopulating activity is poorly understood and cannot be readily modulated. Thus, we are analyzing the function and regulation of GATA transcription factors that control hematopoietic stem cell function, hematopoiesis, the function of specific blood cell types, and additional important biological processes. We demonstrated that GATA-1 and GATA-2 select a small subset of DNA motifs within the genome and function via multiple mechanisms to control target gene expression. Transcriptional profiling and chromatin immunoprecipitation coupled with microarray analysis have identified a large 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, and cultured cells to elucidate GATA factor networks, which will provide fundamental insights into mechanisms of development and cellular differentiation. Furthermore, this knowledge can be exploited to develop novel approaches to therapeutically modulate hematopoietic stem cells, hematopoiesis, and blood cell malignancies.
| Another program focuses on the transcriptional control of hemoglobin synthesis. These studies address fundamental mechanistic questions on how chromatin modification/remodeling regulates transcription of endogenous loci. Whereas a great deal is known about DNA assembly into nucleosomal filaments and higher-order chromatin structure, many questions remain unanswered regarding how dynamic changes in chromatin structure are orchestrated during development and cellular differentiation. |
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We have defined a novel multistep chromatin domain activation mechanism and are continuing to establish precisely how broad regions of repressed chromatin are converted into transcriptionally permissive and active chromatin. We are also interested in understanding the molecular underpinnings of hemoglobinopathies, which result from dysregulation of transcriptional mechanisms that control hemoglobin synthesis, and devising strategies to treat such diseases.
Based on our discovery of an endogenous suppressor of angiogenesis, which functions via a novel multi-component mechanism, we are developing strategies to inhibit and promote angiogenesis, the process whereby new blood vessels develop from preexisting vasculature. Angiogenesis is a fascinating process that has crucial physiological functions and underlies specific pathophysiologies, such as cancer, macular degeneration, and diabetic retinopathy, which affects millions of people worldwide. Anti-angiogenic therapy has emerged as an efficacious strategy to treat these diseases and holds enormous promise for promoting vascularization of bioengineered tissues to prevent tissue rejection, facilitating the repair of ischemic damage in the heart, and facilitating the repair of stroke-induced damage in the central nervous system. Furthermore, as GATA-2 has important functions in vascular endothelium and its deregulation is linked to human coronary artery disease, we are also defining how GATA-2 functions in the context of the vascular system. This work, in conjunction with studies on Notch receptor structure/function analyses, constitutes emerging efforts in vascular biology.
Selected Publications: Articles on PubMed
- Lurie LJ, Boyer ME, Grass JA, Bresnick EH. (2008). Differential GATA factor stabilities: implications for chromatin occupancy by structurally similar transcription factors. Biochemistry. 47:859-869. PMID 18154321
- Kim S-I and Bresnick EH. (2007). Transcriptional control of erythropoiesis: emerging mechanisms and principles. Oncogene. In press.
- Wu J and Bresnick EH. (2007). Bare rudiments of Notch signaling: how receptor levels are regulated. Trends in Biochemical Sci. In press.
- Lugus JJ, Chung YS, Mills JC, Kim SI, Grass J, Kyba M, Doherty JM, Bresnick EH, and Choi K. (2007). GATA2 functions at multiple steps in hemangioblast development and differentiation. Development. PDF. PMID 17166922
- Johnson KD, Boyer ME, Kang JA, Wickrema A, Cantor AB, and Bresnick EH. (2007). Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function. Blood. PDF.PMID 17339418
- Wozniak RJ, Boyer ME, Grass JA, Lee Y, and Bresnick EH. (2007). Context-dependent GATA factor function: Combinatorial requirements for transcriptional control in hematopoietic and endothelial cells. J Biol Chem. PDF. PMID 17347142
- Kim SI, Bultman S, Jing H, Blobel GA, and Bresnick EH. (2007). Dissecting molecular steps in chromatin domain activation during hematopoietic differentiation. Mol Cell Biol. PDF PMID 17438135
- Im H, Grass JA, Johnson
KD, Kim SI, Boyer ME, Imbalzano AN, Bieker JJ, Bresnick EH. (2005).
Chromatin domain activation via GATA-1 utilization of a small subset
of dispersed GATA motifs within a broad chromosomal region. PNAS
USA. 102:17065-70. PDF PMID 16286657
- Johnson K, Christensen
H, Zhao B, and Bresnick EH. (2001). Distinct mechanisms control RNA
polymerase II recruitment to a tissue-specific locus control region
and a downstream promoter. Mol Cell. 8:65-471. PDF PMID 11545748
View More Publications
Lab Members
Undergraduate Students:
- Ben Moore - Freshman at
UW-Madison
- Erin M. Riley - Sophomore
at UW-Madison, double major in Bacteriology and French Horn Performance
- Tuan Tran - Sophomore at UW-Madison, Biomedical Engineering
Senior Scientists:
- Kirby Johnson - Assistant
Scientist, Ph.D. Genetics, University of Wisconsin
Graduate Students:
- Shin-Il Kim - M.S. Immunomodulation Research Center (IRC), University of Ulsan
- Sherry Lee - M.S. Boston University
- James Pope, B.S. Biochemistry/Engineering, University of Texas-Austin
- Yoon A Kang
Postdoctoral Fellows:
- Ryan Wozniak - Ph.D., Pharmacology,
University of Arizona Medical School
- Bidesh Mahata - Ph.D. Biochemistry, India Institute of Chemical Biology
- Tohru Fujiwara, MD, Ph.D., Tohoku University
Research Associates:
- Meghan Boyer - BS, UW-Madison
Graduate Student Alumni:
- Dr.
Lloyd Lam - scientist in Louis Staudt's laboratory at
National Institutes of Health (NIH)
- Dr.
E. Camilla Forsberg - completed postdoctoral studies with Dr. Irving Weissman at Stanford and is now an Assistant Professor of Biomolecular Engineering at UC-Santa Cruz
- Dr.
Janny Chu - completed postdoctoral studies with Dr. Stuart Orkin at Harvard Medical School and is now a Senior Scientist, Advanced Cell Technology
- Hogune Im - postdoctoral
fellow in Michael Snyder's laboratory at Yale
- Melissa Martowicz - postdoctoral
fellow in Wes Pike's laboratory at University of Wisconsin-Madison
- Jing Wu - Postdoctoral fellow in Laurie Glimcher's laboratory at Harvard Medical School
- Louis Lurie - Applying to medical school
Postdoctoral Alumni:
- Wayne Versaw - Assistant
Professor of Biology, Texas A and M University
- Karen Gould - Assistant
Professor of Genetics, University of Nebraska Medical Center
- Kai Huang - Staff Scientist,
University of Toronto
- Soumen Paul - Assistant Professor of Pathology, University of Kansas School of Medicine
Recent Invited Lectures:
Naito Foundation Symposium: Nuclear Dynamics and RNA, Japan, 2008
16th International Hemoglobin Switching Meeting, Asilomar, CA, 2008
American Society of Hematology, San Francisco, CA, 2008
University of Montreal, September, 2007
Red Cell Gordon Conference, France, 2007
Loyola University, Cardinal
Bernardin Cancer Center, 2007
4th International GATA
factor meeting, Capri, Italy, 2007
Johns Hopkins University
School of Medicine, Department of Pharmacology and Molecular Sciences,
2007
Yale University, Department
of Genetics, 2006
15th International Hemoglobin
Switching Meeting, Oxford, 2006
Yale University, Center
for Molecular Hematology, 2006
Kansas University School
of Medicine, 2006
American Society of Hematology,
New Orleans, LA, December 2005
University of Cincinnati,
November, 2005
Red Cell Gordon Conference,
Tilton, NH, June, 2005
Morehouse College of Medicine,
Cardiovascular Center, January, 2005
Workshop on Myeloid Development,
San Diego, CA, December, 2004
Fourteenth International
Hemoglobin Switching/Hematopoiesis Meeting, Orcas Island, WA, September
7, 2004
National Institutes of
Health, April, 2004
Maine Medical Center, March,
2004
Recent Study Section Service:
Chair, NIH Erythrocyte
and Leukocyte Biology Study Section, 2005-2007
Member of NIH Study Section
Erythrocyte and Leukocyte Biology, 2003-2007
http://www.innovationsreport.de/html/berichte/biowissenschaften_chemie/bericht-19911.html
Germany - "Innovations Report"
http://www.eurekalert.org/pub_releases/2003-07/uow-rfm071403.php
United States - New release web site
Emery Bresnick, Ph.D.
Department of Pharmacology
383 Medical Sciences Center
1300 University Avenue
Madison, WI 53706
TEL. (608) 265-6446
FAX (608) 262-1257
E-Mail - ehbresni@wisc.edu
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