Gender	Female
E-mail	margaret.baron@mssm.edu
Education and Training	M.D., Harvard Medical School
	Ph.D., Massachusetts Institute of Technology
	A.B., Harvard University
	Postdoctoral Fellowship, Harvard University
	Resident, Massachusetts General Hospital
Awards	2004 Research Recognition Award American Cancer Society
	2001 - Present Irene and Dr. Arthur M. Fishberg Professor of Medicine in Hematology
	2000 Elected Member American Society for Clinical Investigation [ASCI]
	1989 - 1992 Basil O'Connor Scholar Award March of Dimes
	1987 - 1994 Lucille P. Markey Charitable Trust Scholar Award

Margaret H. Baron, MD PhD, is Fishberg Professor of Medicine in Hematology, Director of Hematology and Medical Oncology Research, and a member of the Black Family Stem Cell Institute (BFSCI). Dr. Baron served as interim Co-Director of the BFSCI for 18 months with Dr. J. Bieker. Dr. Baron is an established scientist who has nearly 20 years of continuous, independent NIH-sponsored research funding in hematopoiesis and a publication record spanning protein biochemistry, virology, cell biology, developmental biology, and stem cell biology. She is well-known for her work on the plasticity of the differentiated state, globin gene regulation, and developmental hematopoiesis.

Dr. Baron is a graduate of the Harvard-M.I.T. Program in Health Sciences and Technology (H.S.T.) and holds degrees from Harvard (A.B.), Harvard Medical School (M.D.) and M.I.T. (Ph.D.). She trained in the laboratories of David Baltimore (Ph.D. thesis) and Tom Maniatis (postdoc). Her first independent faculty position was in The Biological Laboratories at Harvard U., where she spent 8 years as an assistant and then associate professor before moving to a tenured position at Mount Sinai in 1997, with an important goal of helping to expand the hematopoiesis and stem cell biology research programs at her new institution.

Dr. Baron is a dedicated educator, having developed and directed courses for Ph.D. students at Harvard and at Mount Sinai. She is a member of the Steering Committee for the Graduate School of Biological Sciences, has served as an Assistant Director of the Medical Scientists Training Program (MSTP) and as Co-Director for the former Mechanisms of Disease and Therapies Multidisciplinary Training Area (MTA) and is co-founder and Co-Director for a new training program for Ph.D. and M.D./Ph.D. students in "Developmental and Stem Cell Biology."

To read more about Dr. Baron's research, please visit the Baron Laboratory website.

Education and Training	M.D., Harvard Medical School
	Ph.D., Massachusetts Institute of Technology
	A.B., Harvard University
	Postdoctoral Fellowship, Harvard University
	Resident, Massachusetts General Hospital

Specific Clinical/Research Interests: Induction and specification of mesoderm and endoderm in the embryo; development of the mammalian blood and vascular systems; stem cell biology; signaling between erythroid cells and other cell types within different developmental niches; enucleation of red blood cells; disorders of red blood cell development; transcriptional regulation of development and differentiation

Current Students: Ph.D.: (Universite de Paris VII) Elsa Abdoun

Postdoctoral Fellows: Joan Isern, Stuart Fraser, Hailan Zhang, Zhiyong He, Cristian Papazoglu, Rebecca Moore

Research Personnel: Kate Dziedzic, Maisha Nelson

Current Research Studies
Dr. Baron's research program combines multiple complementary approaches to study the mechanisms by which cell fate decisions are regulated in stem and progenitor cells, with a focus on hematopoiesis and vascular development. Our lab developed a novel explant culture assay to show that signaling interactions between endoderm and mesoderm play a role in hematopoietic and vascular induction in the early mouse embryo. One such signal, Indian hedgehog (Ihh), may function, in part, through upregulation of Bone Morphogenetic Protein 4 (BMP4).

One target of the BMP pathway is the homeodomain transcription factor, Mix-like (Mixl). We discovered that conditional induction of mMixl in differentiating murine embryonic stem (ES) cells results in acceleration of the entire mesodermal developmental program and in increased numbers of mesodermal, hemangioblastic, and hematopoietic progenitors, suggesting that mMixl functions early in the recruitment and/or expansion of mesodermal progenitors to the hemangioblastic and hematopoietic lineages. Genetically manipulated ES cells and mouse models in which Mixl is conditionally activated or deleted are being used to investigate the earliest events in mesoderm sp ecification. Biochemical approaches and gene expression profiling are being used to study the transcriptional activities and targets of mMixl. These studies may suggest new approaches for cell replacement therapies.

The yolk sac (YS) is the first developmental niche of the mammalian embryo, yet the production of hematopoietic stem and progenitor cells in this tissue is barely understood. In the mouse, primitive erythroid cells (EryP) arise in large numbers from YS-derived progenitors around the end of gastrulation, enter the circulation two days later, and continue to mature in a stepwise and synchronous fashion. We have developed transgenic (Tg) mouse systems in which fluorescent proteins are expressed exclusively in EryP, allowing the tagging and tracking of these cells and their nuclei throughout gestation. Unexpectedly, we found that EryP mature and enucleate within a niche (the fetal liver, FL) that is distinct from the one in which they first arise (YS). To sample their transcriptome during development, EryP were FACS sorted from staged embryos from E8.5 (YS) through E11.5 (circulation and FL stages).

Our analysis included populations that contain (E8.5) or have lost (E9.5 and on) EryP progenitor activity. This Tg mouse system allowed us to enrich for and isolate, for the first time, progenitors of the EryP lineage. Genes whose expression changes during the progression from progenitor to maturing erythroblast cluster according to nine major patterns encompassing distinct functional classes. We have identified novel growth factor requirements and transcriptional regulators for EryP progenitor maintenance and/or expansion and for their maturation. Analysis of the genes within the various functional groups suggest reciprocal interactions between EryP and other cells within the YS and FL niches. We have developed additional Tg mouse models to monitor and purify major cell populations from these niches. While we have focused initially on the development of EryP, insights from our microarray studies can also be applied to the emergence of the first adult type (definitive) hematopoietic stem and progenitor cells.

Non-Mesodermal Activators of Hematopoiesis and Vasculogenesis in the Mouse Embryo
Approaches:
Mouse Models
Transgenic Embryo Explant Culture Assays
Genetically Manipulated Embryonic Stem (ES) Cells

Bone Morphogenetic Proteins (BMPs) in Embryonic and Adult Hematopoiesis
Approaches:
Mouse Models
Transgenic Embryo Explant Culture Assays
Genetically Manipulated Embryonic Stem (ES) Cells

Novel Regulators of Human and Mouse Hematopoietic Stem Cells: in Vitro and in Vivo Approaches

Cloning, Expression and Function of Murine and Human Homologues of Xenopus Mix Genes
Approaches:
Mouse Models (transgenic and knockout; in progress)
Overexpression of Wild Type and Mutated Forms in Embryonic Stem (ES) Cells;
Analysis of Effect on Differentiation in Vitro
Analysis of Transcriptional Regulation Function and Interactions with Other Proteins in Vitro and in Vivo (cultured cells, embryoid bodies)

DNA Array Analysis of Gene Expression Patterns in Stem and Progenitor Cells

For more information, please visit the Baron Laboratory website.

Isern J, Fraser ST, He Z, Baron MH. The fetal liver is a niche for maturation of primitive erythroid cells. Proc Natl Acad Sci USA 2008; 105: 6662-6667.

Baron MH. The wanderings of hematopoietic stem cells. Blood 2008; 111: 3307-3308.

Durand C, Robin C, Bollerot K, Baron MH, Ottersbach K, Dzierzak E. Embryonic stromal clones reveal developmental regulators of definitive hematopoietic stem cells. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 20838-20843.

Haremaki T, Fraser ST, Kuo YM, Baron MH, Weinstein DC. Vertebrate Ctr1 coordinates morphogenesis and progenitor cell fate and regulates embryonic stem cell differentiation.. Proc. Natl. Acad. Sci. U.S.A 2007; 104: 12029-12034.

Fraser ST, Isern J, Baron MH. Maturation and enucleation of primitive erythroblasts is accompanied by changes in cell surface antigen expression patterns during mouse embryogenesis. Blood 2007; 109: 343-352.

Kwon G, Fraser ST, Eakin G, Mangano M, Isern J, Hadjantonakis AK, Baron MH. Tg(Afp-GFP) Expression Marks Primitive and Definitive Endoderm Lineages during Mouse Development. Developmental Dynamics 2006; 235: 2549-2558.

Willey S, Ayuso-Sacido A, Zhang H, Fraser ST, Adlam MA, Sahr K, Kyba M, Daley GQ, Keller G, Baron MH. Acceleration of Mesoderm Development and Expansion of Hematopoietic Progenitors in Differentiating ES Cells by the Mouse Mix-Like Homeodomain Transcription Factor. Blood 2006; 107: 3122-3130.

Baron MH. Early Patterning of the Mouse Embryo: Implications for Hematopoietic Commitment and Differentiation. Experimental Hematology 2005; 33: 1015-1020.

Fraser ST, Hadjantonakis K, Willey S, Sahr KE, Kelly OG, Jones EV, Dickinson ME, Baron MH. Using a Histone Yellow Fluorescent Protein Fusion for Tagging and Tracking Endothelial Cells in ES Cells and Mice. Genesis 2005; 42: 162-171.

Fraser ST, Baron MH. The Specification of Early Hematopoiesis in the Mammal. Current Opinion in Hematology 2005; 12: 217-221.