LABORATORY OF BLOOD

CELL  DEVELOPMENT


Dr. Stuart Fraser

Discipline of Physiology,

School of Medical Sciences

University of Sydney,

Room 233,

Medical Foundation Building K25

92-94 Parramatta Road


stuart.fraser@sydney.edu.au

 
 

We are interested in how the blood (or hematopoietic) lineages form in the embryo.

Blood is essential for life and the development of the hematopoietic lineages during embryogenesis is not well understood.

We use several systems to analyse hematopoietic development


*Mouse embryos.The mouse embryo develops from fertilised zygote to pup in 20 days. We look at where, when and under conditions blood cells appear. This includes the very first blood cell, the primitive red blood cells (see the top panels below). We also examine how hematopoietic stem  cells are first generated in the mouse embryo. Knockout mice are also a useful system for studying developmental processes. The panel shows
a mutant mouse with severe problems in blood vessel formation.


We also purify early red blood cell and stem cell populations in the mouse embryo to characterise the processes and events necessary during blood cell development.



*The adult bone marrow. In the adult, the blood is produced constantly in the bone marrow. We produce 2 million new red blood cells each second. The final stage of red blood cell maturation requires the nucleus to be condensed and expelled. This process, called enucleation, is poorly defined.


*Embryonic stem (ES) cells are derived from early embryos and can be induced to differentiate into many different cell types. We use this as a model to examine the molecular mechanisms that regulate blood and blood vessel development. In particular, we are interested in the mechanisms that determine whether cells remain as stem cells or differentiate.


*Evolutionary developmental biology of blood cell production. We have recently made some exciting findings using a new animal model of red blood cell production. We will explore this model further to ask a fundamental question in blood cell generation, why do mammalian red blood cells condense and expel their nuclei?


If any of these projects capture your interest, feel free to contact Dr. Fraser. We regularly have undergraduate students in the lab to gain lab experience. Students interested in doing Honours or post-graduate studies in the lab are always welcome.


Lab members:

Dr. Stuart Fraser

Dr. Angeles Sanchez-Madrid: Senior Research Associate

Miss Veronica Antas: Masters Student



Dr. Stuart Fraser

1988-1992:     B.Sc (Honours), Monash University, Melbourne, Australia

1993-1998:    Ph.D, Biochemistry, University of Hong Kong, Hong Kong

1998-2002:    Post-doctoral Fellow, Molecular Genetics, Kyoto University, Kyoto, Japan

2002-2004:    Research Fellow, Institute for Toxicology, Johannes Gutenberg University, Mainz, Germany

2004-2010:     Assistant Professor, Hematology/Medical Oncology, Black Family Stem Cell Institute,

                       Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, USA

2010-present: Lecturer, Physiology, School of Medical Sciences, Bosch Institute,            

                        University of Sydney, Australia


Selected publications

Isern J, He Z, Fraser ST, Nowotschin S, Ferrer-Vaquer A, Moore R, Hadjantonakis AK, Schulz V, Tuck D, Gallagher PG, Baron MH. Single-lineage transcriptome analysis reveals key regulatory pathways in primitive erythroid progenitors in the mouse embryo. Blood. 2011 May 5;117(18):4924-34


Isern, J., Fraser, S. T., He, Z. and Baron, M. H. (2010) Developmental Niches for embryonic erythoid cells. Blood Cells Mol Dis. Apr 15;44(4):207-8.

Fraser, S.T. and Baron M.H. Embryonic fates for extracellular lineages: new perspectives. J. Cell Biochem. 2009, Jul 1;107(4):586-91.

Zhang, H., Fraser, S.T., Papazoglu, C., Hoatlin, M. and Baron, M.H. (2009). Transcriptional activation by the Mixl1 Homeodomain Protein in differentiating mouse embryonic stem cells. Stem Cells. Dec;27(12):2884-95.

Isern, J., * Fraser, S.T., He, Z. and Baron, M.H. (2008) The fetal liver is a niche for maturation of primitive erythroid cells. Proc. Natl. Acad. Sci. U.S.A. 105, 6662-6667. [Also see "This Week in PNAS/In This Issue"] *co-first author

Roos, W.P., Christmann, M., Fraser, S.T., Kaina, B. (2007) Mouse embryonic stem cells are hypersensitive to apoptosis triggered by the DNA damage O(6)-methylguanine due to high E2F1 regulated mismatch repair. Cell Death Differ. 14: 1422-1432

Haremaki, T., Fraser, S.T., Kuo, Y.-M., Baron, M.H., and Weinstein, D.C. (2007) Vertebrate Ctr1 coordinates morphogenesis and progenitor cell fate and regulates embryonic stem cell differentiation. Proc. Natl. Acad. Sci. U.S.A. 104: 12029-12034.

Fraser, S.T., Isern, J. and Baron, M.H. (2007) Maturation and enucleation of primitive erythroblasts is accompanied by changes in cell surface antigen expression patterns during mouse embryogenesis. Blood 109: 343-352.

Willey, S., Ayuso-Sacido, A., Zhang, H., Fraser, S.T., Adlam, M.A., Sahr, K., Kyba, M., Daley,  G.Q., Keller, G., and Baron, M.H. (2006) Acceleration of Mesoderm Development and Expansion of Hematopoietic Progenitors in Differentiating ES Cells by the Mouse Mix-Like Homeodomain Transcription Factor. Blood /blood-2005-10-4120.

Kwon, G.S., Fraser, S.T., Eakin, G.S., Mangano, M., Isern, J., Hadjantonakis, A.-K., and Baron, M.H. (2006) AFP::GFP Transgene Expression Marks Primitive and Definitive Endoderm Lineages during Mouse Development.  Developmental Dynamics 235:2549-2558.

Baron, M.H. and S.T. Fraser. The specification of early hematopoiesis in the mammal. Curr Opin Hematol. 2005 May;12(3):217-21.

Fraser, S.T., A. K. Hadjantonakis, K. E. Sahr , S. Willey, O. G. Kelly,  E. A. Jones, M. E. Dickinson and M. H. Baron. Using a histone yellow fluorescent protein fusion for tagging and tracking endothelial cells in ES cells and mice. Genesis. 2005. 42(3):162-17.

Schroeder, T., S.T. Fraser, M. Ogawa, S. Nishikawa, C. Oka, G. Bornkamm, S.-I. Nishikawa, T. Honjo and U. Just. Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis. Proc. Natl. Acad. Sci. U.S.A. 2003 1:100 (7): 4018-23.

Fraser, S.T., M. Ogawa, T. Yokomizo, Y. Ito, S. Nishikawa and S.-I. Nishikawa. Putative intermediate precursor between hematogenic endothelial cells and blood cells in the developing embryo. Dev. Growth Differ 2003 45, 10:63-75.

Fraser, S.T., J. Yamashita, L.M. Jakt, M. Okada, M. Ogawa, S. Nishikawa and S.-I. Nishikawa. n vitro Differentiation of Mouse Embryonic Stem Cells: Hematopoietic and Vascular Cell Types. Methods in Enzymology, 2003, 365:59-72.

Fraser, S.T., M. Ogawa, R.T. Yu, S. Nishikawa, M.C. Yoder and S.-I. Nishikawa. 2002 Definitive hematopoietic commitment within the embryonic Vascular Endothelial-Cadherin+ population. Exp. Hematol. 30(9): 1070-7.

Bockamp, E., M. Maringer, C. Spangenberg, S. Fees, S.T. Fraser, L. Eshkind and B. Zabel. 2002.  Of mice and models: towards better animal models. Physiological Genomics. 3;11(3):115-32.

Hashi, H., H. Yoshida, K. Honda, S.T. Fraser, M. Awane, A. Takabayashi, H. Nakano, Y. Yamaoka and S. Nishikawa. 2001 Compartmentalization of Peyers Patch anlagen before lymphocyte entry. J. Immunol. 166: 3702-3709








 
Mouse embryonic blood cells at  mid-gestation.