Margaret A. Goodell, Ph.D.
Director, STaR Center
Associate Professor, Baylor College of Medicine
Center for Cell & Gene Therapy
One Baylor Plaza, Room N1030
Houston, TX 77030
713-798-1265
Lab: 713-798-1271
Fax: 713-798-1230
E-mail: goodell@bcm.edu
Education
B.S., Imperial College of Science and Technology, London, England, 1986
Ph.D., University of Cambridge, England, 1991
Postdoc, Whitehead Institute, Massachusetts Institute of Technology, 1996
Postdoc, Harvard Medical School, Boston, MA, 1997
Research Interest
Hematopoietic Stem Cells
Normal Hematopoietic Stem Cell Biology
A major focus of Dr. Goodell's laboratory is the molecular regulation of hematopoietic stem cells (HSC). Her laboratory has sought to identify the genes that are responsible for maintaining the quiescent state of HSC, as well as their self renewal. A single injection of the chemotherapeutic agent 5-Fluoruracil (5FU) kills rapidly dividing progenitors in the bone marrow, and activates HSC, causing some to differentiate, regenerating the hematopoietic system, and others to self-renew. Using microarrays to examine gene expression changes over a time-course of activation, the laboratory has identified cohorts of genes that appear to be involved in activating self-renewal of the HSC. The laboratory is now examining the role of specific genes in the self-renewal and activation cycle. A long-term goal of these studies is to elucidate the genes required for HSC self-renewal, with the goal of determining conditions that would allow HSC to be expanded in vitro without differentiation, a long-sought goal of hematological research that could have enormous impact on the practice of bone marrow transplantation. A second major goal is to broadly understand growth regulation of normal stem cells, with the expectation that insights into regulation of normal stem cells would also apply to regulation of quiescence and activation of putative tumor stem cells.
Hematopoietic stem cells in aging
Stem cells replenish the cells of aging tissues, and can thus act as a barrier against some of the affects of age. However, hematopoietic stem cells from older mice have been shown to have diminished function, suggesting that they themselves may age. The Goodell laboratory is examining the molecular changes in hematopoietic stem cells that may account for these functional changes, by profiling gene expression in purified stem cells over a time-course of aged mice. Many broad changes are observed, including some seen in other aging systems. Current efforts will are directed to identifying genes that are regulate the aging process, as opposed to those that are simple markers of aging.
Generation of hematopoietic cells from human embryonic stem cells
Human ES (hES) cells can expand indefinitely and differentiate to all known somatic cells types, including blood. Human bone marrow stem cells made from hES could be used for bone marrow transplantation to make patients histocompatible to additional therapeutic cell types made from hES. Hematopoietic components differentiate from hES, albeit only inefficiently. The laboratory is investigating genes that may regulate hematopoietic differentiation from hES, with a view to either selecting differentiating hematopoietic cells, or enhancing hematopoietic differentiation by forced expression of specific hematopoietic regulators.
Selected Publications
Jackson KA, Mi T, Goodell MA (1999) Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proceedings of National Academy of Sciences U.S.A. 96:14482-14486.
Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA (2002) Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Developmental Biology 245:42-56.
Camargo FD, Green R, Capetenaki Y, Jackson KA, Goodell MA (2003) Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nature Medicine 9:1520-1527.
Venezia, T. A., A. A. Merchant, C. A. Ramos, N. L. Whitehouse, A. S. Young, C. A. Shaw and M. A. Goodell (2004). Molecular signatures of proliferation and quiescence in hematopoietic stem cells. PLoS Biol 2: e301.