William M. Miller
As a chemical and biological engineer, I have been conducting research in hematopoietic cell culture for more than 20 years with nearly 50 publications in this field. I also have extensive experience culturing hematopoietic cells in various types of bioreactors and in developing surfaces for the selective presentation of cell adhesion molecules. My research has focused on how the culture environment (pH, pO2, osmolality, lipids, surfaces, etc.) impacts cell growth, differentiation, and protein production and quality. Recent research has focused on the production of high-ploidy megakaryocytic cells and platelets for potential applications in cell therapy and platelet transfusions, as well as the mechanisms by which nicotinamide increases megakaryocytic cell ploidy. My group also investigates the signal transduction pathways involved in granulocytic and erythroid cell differentiation and, especially, megakaryocytic cell differentiation and polyploidization. We take inspiration from the hematopoietic stem cell niche to develop culture conditions for stem and progenitor cell expansion and controlled differentiation into diverse hematopoietic lineages. We extensively use flow cytometry for phenotypic characterization via cell surface marker expression; cell cycle analysis; assessment of viability, apoptosis, and reactive oxygen species (ROS) content; as well as signal transduction and functional activity. Earlier research in my lab investigated the effects of dietary lipids on the growth and metabolism of breast cancer cell lines and employed NMR to evaluate nucleotide sugar metabolism in small cell lung cancer cells. We have also extensively evaluated the effects of the culture environment on the production of model biotherapeutic proteins including monoclonal antibodies. Hematopoietic cells produced in culture have the potential to ameliorate chemotherapy-induced cytopenias, as well as to induce tolerance in recipients of organ transplants from the same donors. A better understanding of normal hematopoietic cell differentiation may also contribute to the treatment of abnormal differentiation in myeloid leukemias. Finally, we are also developing bioreactor systems to support the recellularization of decellularized organs with the aim of augmenting the supply of organs for liver and kidney transplantation.
Dual-Purpose Bioreactors to Monitor Noninvasive Physical and Biochemical Markers of Kidney and Liver Scaffold Recellularization. Uzarski JS, Bijonowski BM, Wang B, Ward HH, Wandinger-Ness A, Miller WM, and Wertheim JA. Tissue Engineering Part C: Methods. 2015 October 1;21(10):1032-1043.
Epithelial Cell Repopulation and Preparation of Rodent Extracellular Matrix Scaffolds for Renal Tissue Development. Uzarski JS, Su J, Xie Y, Zhang ZJ, Ward HH, Wandinger-Ness A, Miller WM, and Wertheim JA. Journal of Visualized Experiments. 2015 August 10;102:e53271.
Separation of in-vitro-derived megakaryocytes and platelets using spinning-membrane filtration. Schlinker AC, Radwanski K, Wegener C, Min K, and Miller WM. Biotechnology and Bioengineering. 2015 April;112(4):788-800.
Human megakaryocyte progenitors derived from hematopoietic stem cells of normal individuals are MHC class II-expressing professional APC that enhance Th17 and Th1/Th17 responses. Finkielsztein A, Schlinker AC, Zhang L, Miller WM, and Datta SK. Immunology Letters. 2015 January;163(1):84-95.
Dynamic transcription factor activity profiles reveal key regulatory interactions during megakaryocytic and erythroid differentiation. Duncan MT, Shin S, Wu JJ, Mays Z, Weng S, Bagheri N, Miller WM, and Shea LD. Biotechnology and Bioengineering. 2014 October;111(10):2082-2094.
Profiling Deacetylase Activities in Cell Lysates with Peptide Arrays and SAMDI Mass Spectrometry. Kuo H-Y, DeLuca TA, Miller WM, and Mrksich M. Analytical Chemistry. 2013 November 19;85(22):10635-10642.
Three-Stage Ex Vivo Expansion of High-Ploidy Megakaryocytic Cells: Toward Large-Scale Platelet Production. Panuganti S, Schlinker AC, Lindholm PF, Papoutsakis ET, and Miller WM. Tissue Engineering Part A. 2013 April;19(7-8):998-1014.
Administration of nicotinamide does not increase platelet levels in mice. Konieczna IM, Panuganti S, DeLuca TA, Papoutsakis ET, Eklund EA, and Miller WM. Blood Cells, Molecules, and Diseases. 2013 March;50(3):171-176.
Bioreactor design for perfusion-based, highly vascularized organ regeneration. Bijonowski BM, Miller WM, and Wertheim JA. Current Opinion in Chemical Engineering. 2013 February;2(1):32-40.
Energy, Water and Fish: Biodiversity Impacts of Energy-Sector Water Demand in the United States Depend on Efficiency and Policy Measures. McDonald RI, Olden JD, Opperman JJ, Miller WM, Fargione J, Revenga C, Higgins JV, and Powell J. PLoS ONE. 2012 November 21;7(11):e50219.
View all publications by William M. Miller listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.