Margaret A. Goodell

Hematopoietic stem cells: basic biology and gene therapy

• Hematopoietic Stem Cell Biology:
  
  We are interested in the basic biology of hematopoietic stem cells. It has been known for decades that hematopoietic stem cells reside in the bone marrow in a quiescent state and replenish the supply of differentiated cells of the peripheral blood throughout the lifetime of an animal. No other adult cell type retains the capacity for such immense proliferation and differentiation. However, little is known about the cells or factors that regulate their primitive state or control their activation. We study the behavior of these stem cells in vivo and in vitro using mouse stem cells as a model, as well as pursue the mechanisms which controls their behavior on a molecular level.
  
  
• Human Hematopoietic Stem Cells and Gene Therapy:
  
  We also study human hematopoietic stem cells. Human bone marrow stem cells are conventionally defined by their expression of the antigen CD34. We discovered that a population of putative stem cells exists in adult human bone marrow that may lack this marker. We are studying these cells in normal and leukemic bone marrow to determine their normal role in human hematopoiesis. We are also interested in using these cells as vehicles for gene therapy, and thus are determining the most effective methods to deliver genes to this primitive population.
  
  
• Stem Cell Plasticity:
  
  Over the past three years, work from a number of laboratories including our own has led to the idea that stem cells derived from adult tissues, particularly the hematopoietic system, may be able to differentiate outside their tissue of origin thereby contributing to regeneration of distal tissues. We study this phenomenon by focusing on a hematopoietically active stem cell population obtained from murine skeletal muscle, and also by examining the potential of bone marrow-derived stem cells to differentiate into cardiomyoctes and endothelial cells. Ongoing research seeks to understand the precise identity of the cells involved in the regeneration process and the mechanisms which regulate their differentiation.

Selected Publications

McKinney-Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F, Goodell MA (2002) Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proceedings of National Academy of Sciences U.S.A. 99:1341-1346.

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, Capetanaki Y, Jackson KA, Goodell MA (2003) Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nature Medicine 9:1520-1527.

Camargo FD, Chambers SM, Goodell MA (2004) Stem cell plasticity: from transdifferentiation to macrophage fusion. Cell Proliferation 37:55-65.

Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, Goodell MA (2007) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biology 5:e201.

Chambers SM, Boles NC, Lin KY, Tierney MP, Bowman TV, Bradfute SB, Chen AJ, Merchant AA, Sirin O, Weksberg DC, Merchant MG, Fisk CJ, Shaw CA, Goodell MA (2007) Hematopoietic fingerprints: an expression database of stem cells and their progeny. Cell Stem Cell 1:578-591.

Feng CG, Weksberg DC, Taylor GA, Sher A, Goodell MA (2008) The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation. Cell Stem Cell 2:83-89.

Weksberg DC, Chambers SM, Boles NC, Goodell MA (2008) CD150^– side population cells represent a functionally distinct population of long-term hematopoietic stem cells. Blood 111:2444-2451.

Contact Information

Margaret A. Goodell, Ph.D.

Center for Cell and Gene Therapy

Baylor College of Medicine

One Baylor Plaza N1030

Houston, Texas 77030, U.S.A.

Lab Website

Tel: (713) 798-1265

Fax: (713) 798-1230

E-mail: goodell@bcm.edu