Personal HistoryMy research focus is the gene regulatory basis of stem cell fate choice. Published work from my laboratory showed that major, conserved signal transduction pathways regulate the expression of key stem cell factors to control hematopoietic stem-like cell multipotency and differentiation in the fly. Additional reports from my laboratory showed that the conserved hematopoietic factors, GATA, Friend of GATA and Runx interact to control the cell fate choice of a blood lineage precursor. As a postdoctoral fellow, I helped to establish Drosophila as a model organism for the study of organogenesis by demonstrating that several conserved pathways control heart and blood cell development, thereby making important contributions to the study of gene regulation of organogenesis and stem cell biology. My work in stem cell biology and hematopoiesis has been funded by an Institutional Research Grant from the University of Texas M.D. Anderson Cancer Center, a Scientist Development Grant from the American Heart Association, a National Institutes of Health R01 Grant and Administrative Supplement, and an Institutional Research Grant from the University of Maryland School of Medicine. I am a member of the University of Maryland School of Medicine Center for Stem Cell Biology and Regenerative Medicine, which is under the direction of Dr. Curt Civin. The Stem Cell Center is designed to foster interactive research between public and private institutions in Maryland. This membership has afforded the opportunity to collaborate and exchange information with other stem cell biologists across the region. I am currently collaborating with 7 members of the Stem Cell Center to establish a multi-species consortium that will include ex vivo and iPS human stem cell cultures, Drosophila, mouse and zebrafish model systems. The consortium will identify and investigate the gene regulatory networks that control the response of stem cells to the changing needs of the organism.
Research InterestsHematopoiesis, Stem cell biology
Hematopoiesis, the most extensively characterized stem cell system, serves as a model for the development of specialized cell types from a single multipotent stem cell. Hematopoietic stem cell (HSC) self-renewal and differentiation are controlled by dynamic gene regulatory networks that connect signals from the micro-environment to the stem cell regulatory machinery. Characterizing these gene regulatory networks is vital to both understanding stem cell biology and the clinical application of stem cell therapy. Our long term goal is to define molecular mechanisms that regulate stem cell multipotency and differentiation. We use the genetically tractable Drosophila model system to rapidly identify and dissect conserved regulatory mechanisms that control stem cell biology. The fly serves as an excellent model for mammalian hematopoiesis because many hematopoietic factors and regulatory pathways are evolutionarily conserved. In particular, the Drosophila blood cell progenitor or prohemocyte shares a number of key characteristics with the mammalian HSC, including quiescence, niche dependence and the capacity to form all the blood lineages. This stem-like cell is maintained by the surrounding micro-environment (niche) through the actions of a number of evolutionarily conserved signal transduction pathways. Our work is has identified key links between signaling pathways and the stem cell regulatory machinery and we are currently characterizing the gene regulatory networks that re-program the stem cell in response to environmental stress.
Gao, H., Wu, X., Fossett, N. (2011) Odd-skipped maintains prohemocyte potency and blocks blood cell development in Drosophila. genesis, The Journal of Genetics and Development (in press).
Gao, H., Wu, X., Fossett, N. (2009) Upregulation of the Drosophila Friend of GATA gene u-shaped by JAK/STAT signaling maintains lymph gland prohemocyte potency. Mol. Cell Bio. 29, 6086-6096.
Frandsen, J.L., Gunn, B., Muratoglu, S., Fossett, N., Newfeld, S.J. (2008) Salmonella pathogenesis reveals that BMP signaling regulates a transcription factor cascade that controls blood cell homeostasis and immune responses in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 105, 14952-14957.
Muratoglu, S., Hough, B., Mon, S. T., Fossett, N. (2007) The GATA factor Serpent cross-regulates lozenge and u-shaped expression during Drosophila blood cell development. Dev. Biol. 311, 636-649.
Tokusumi, T., Russell, M., Gajewski, K., Fossett, N., Schulz, R.A. (2007) U-shaped protein domains required for repression of cardiac gene expression in Drosophila. Differentiation, 75, 166-174. The GATA factor Serpent cross-regulates lozenge and u-shaped expression during Drosophila blood cell development. Dev Biol. 2007 Aug 16; [Epub ahead of print] PMID: 17869239 [PubMed - as supplied by publisher]
Muratoglu S, Garratt B, Hyman K, Gajewski K, Schulz RA, Fossett N. Regulation of Drosophila Friend of GATA gene, u-shaped, during hematopoiesis: A direct role for Serpent and Lozenge. Dev Biol. 2006 Apr 27.
Schulz RA, Fossett N. Hemocyte development during Drosophila embryogenesis. Methods Mol Med. 2005;105:109-22. Review.
Fossett N, Hyman K, Gajewski K, Orkin SH, Schulz RA. Combinatorial interactions of serpent, lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11451-6. Epub 2003 Sep 22.
Fossett N, Schulz RA. Functional conservation of hematopoietic factors in Drosophila and vertebrates. Differentiation. 2001 Dec;69(2-3):83-90. Review.
Fossett N, Schulz RA. Conserved cardiogenic functions of the multitype zinc-finger proteins: U-shaped and FOG-2. Trends Cardiovasc Med. 2001 Jul;11(5):185-90. Review.
Fossett N, Tevosian SG, Gajewski K, Zhang Q, Orkin SH, Schulz RA. The Friend of GATA proteins U-shaped, FOG-1, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7342-7. Epub 2001 Jun 12.