News Releases and More Information:
- Researchers Discover Early Step in Blood Stem Cell Development, 2 December 2013
- Eight professors receive Kellett Mid-Career Awards; 21 February 2013
- New genetic mechanism for controlling blood cell development and blood vessel integrity found; 10 September 2012
For more information:
Organ System/Disease Focus:
Aligned Research Focus:
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
- Hsu AP, Johnson KD, Falcone EL, Sanalkumar R, Sanchez L, Hickstein DD, Cuellar-Rodriguez J, Lemieux JE, Zerbe CS, Bresnick EH, Holland SM. GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/23502222) Blood. 2013 May 9;121(19):3830-7, S1-7. doi: 10.1182/blood-2012-08-452763. Epub 2013 Mar 15.
- Johnson KD, Hsu AP, Ryu MJ, Wang J, Gao X, Boyer ME, Liu Y, Lee Y, Calvo KR, Keles S, Zhang J, Holland SM, Bresnick EH. Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity. (http://www.ncbi.nlm.nih.gov/pubmed/22996659) J Clin Invest. 2012 Oct 1;122(10):3692-704. doi: 10.1172/JCI61623. Epub 2012 Sep 10.
- Bresnick EH, Katsumura KR, Lee HY, Johnson KD, Perkins AS. Master regulatory GATA transcription factors: mechanistic principles and emerging links to hematologic malignancies. (http://www.ncbi.nlm.nih.gov/pubmed/22492510) Nucleic Acids Res. 2012 Jul;40(13):5819-31. doi: 10.1093/nar/gks281. Epub 2012 Apr 5. Review.
- Kang YA, Sanalkumar R, O'Geen H, Linnemann AK, Chang CJ, Bouhassira EE, Farnham PJ, Keles S, Bresnick EH. Autophagy driven by a master regulator of hematopoiesis. (http://www.ncbi.nlm.nih.gov/pubmed/22025678) Mol Cell Biol. 2012 Jan;32(1):226-39. doi: 10.1128/MCB.06166-11. Epub 2011 Oct 24.
- Fujiwara T, O'Geen H, Keles S, Blahnik K, Linnemann AK, Kang YA, Choi K, Farnham PJ, Bresnick EH. Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy. (http://www.ncbi.nlm.nih.gov/pubmed/19941826) Mol Cell. 2009 Nov 25;36(4):667-81. doi: 10.1016/j.molcel.2009.11.001.