Our aim is to understand the regulation of hematopoietic stem cell (HSC) self-renewal (division with no loss in stem cell potential) and lineage commitment. Applications include HSC expansion for transplantation or gene therapy, the selective production of granulocytic and megakaryocytic progenitor and postprogenitor cells to eliminate the nadirs in neutrophil and platelet counts after bone marrow transplants, and the production of culture-derived platelets for transfusions. Two broad thrusts include:

1. Controlled differentiation of HSCs into megakaryocytic cells and granulocytic cells. To do this we are (1) evaluating the effects of oxygen tension, pH, and other culture parameters on progenitor cell expansion and differentiation; (2) using RNA interference (RNAi) to modulate commitment and differentiation; and (3) using DNA microarrays to evaluate the associated changes in gene expression. This project is a collaboration with Prof. E. T. Papoutsakis at the University of Delaware.

2. Niche-mimetic culture surfaces for HSC expansion. HSC self-renewal occurs throughout life in the body, but is very difficult to achieve in culture. The stem cell "niche" in the bone marrow includes HSC association with stromal (accessory) cells and the extracellular matrix (ECM). We are enhancing the prospects for HSC renewal in culture by developing lipid-based and polymer-based surfaces for the presentation of multiple cell adhesion molecule (CAM) ligands and bound growth factors in order to mimic the HSC niche. This project is a collaboration with Prof. P. B. Messersmith in Biomedical Engineering, and combines aspects of materials science (surface preparation and characterization) and stem cell biology (evaluation of HSC responses).

R. C. Gunawan, J. A. King, B. P. Lee, P. B. Messersmith, and W.M. Miller (2007). "Surface Presentation of Bioactive Ligands in a Nonadhesive Background using DOPA-Tethered Biotinylated Poly(Ethylene Glycol)." Langmuir , 23 : 10635-10643.

J. A. King, and W.M. Miller (2007). "Bioreactor Development for Stem Cell Expansion and Controlled Differentiation." Curr. Opin. Chem. Biol. ,   11 : 394-398.

L. T. Huang, C.J. Paredes, E.T. Papoutsakis, and W.M. Miller (2007). "Gene-Expression Analysis Illuminates the Transcriptional Programs Underlying the Functional Activity of Ex-Vivo-Expanded Granulocytes." Physiological Genomics , 31 : 114-125.

D.E. Pascoe, D. Arnott, E.T. Papoutsakis, W.M. Miller, and D.C. Andersen (2007). "Proteome Analysis of Antibody-Producing CHO Cell Lines with Different Metabolic Profiles." Biotechnol. Bioeng. , 98 : 391-410.

P.G. Fuhrken, C. Chen, W.M. Miller, and E.T. Papoutsakis (2007). "Comparative, Genome-Scale Transcriptional Analysis of CHRF-288-11 and Primary Human Megakaryocytic Cell Cultures Provides Novel Insights into Lineage-Specific Differentiation." Exp. Hematol. , 35 : 476-489.

L.M. Giammona, P.G. Fuhrken, E.T. Papoutsakis, and W.M. Miller (2006). "Nicotinamide (Vitamin B3) Increases the Polyploidization and Proplatelet Formation of Cultured Primary Human Megakaryocytes." Br. J. Haematol. , 135 : 554-566.

L.R. Abston and W.M. Miller (2005). "Effects of NHE1 Expression Level on CHO Cell Responses to Environmental Stress." Biotechnol. Prog ., 21 : 562-567.  

View all publications by publications by William M. Miller listed in the National Library of Medicine (PubMed).