William M. Miller Professor of Chemical and Biological Engineering

Research Interests

Human and animal cell culture applications in biotechnology, medicine, and tissue engineering

Ex vivo expansion and controlled differentiation of hematopoietic (blood) stem and progenitor cells for transplantation therapies, with a focus on megakaryocytic (Mk) cells and platelets. We are developing a multi-phase culture system to first expand hematopoietic stem and progenitor cells using chromatin-modifying agents and then differentiate these cells into Mk cells and platelets. We are developing culture surfaces that mimic aspects of the in vivo bone marrow niche to increase Mk differentiation and stimulate platelet release. We investigate mechanisms regulating hematopoietic differentiation, including epigenetics, protein acetylation, and transcription factor activity networks. 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.

Development of bioreactor systems for cell culture and tissue engineering. We are exploring the production of platelet-like particles (PLPs) within a microfluidic bioreactor that utilizes shear forces on Mk cells to generate proplatelets and PLPs. We performed computational fluid dynamics (CFD) analysis of several published platelet microbioreactor systems, and used the results to develop a new bioreactor – with well-defined flow patterns and uniform shear profiles. Furthermore, we showed that modulating shear forces and flow patterns real-time within the system had an immediate and significant impact to proplatelet and PLP generation. By identifying positive operating conditions within a physiologically relevant environment, this new bioreactor will be a useful tool for the study and analysis of proplatelet and PLP formation that will further understanding of ex vivo platelet release. We are developing and characterizing bioreactor systems for the recellularization of organ scaffolds for eventual use in liver and kidney transplantation (with Prof. Jason Wertheim in Transplant Surgery).

Selected Publications

Essential design considerations for the resazurin reduction assay to noninvasively quantify cell expansion within perfused extracellular matrix scaffolds. Uzarski JS, DiVito MD, Wertheim JA, and Miller WM. Biomaterials. 2017 June;129:163-175.

SIRT1 is a critical regulator of K562 cell growth, survival, and differentiation. Duncan MT, DeLuca TA, Kuo H-Y, Yi M, Mrksich M, and Miller WM. Experimental Cell Research. 2016 May 15;344(1):40-52.

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.

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.

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.

View all publications by William M. Miller listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.