Chemical and Biomolecular Engineering Associate Professor Candidate Seminar
Bioinspired Engineering of Human Pluripotent
Stem Cell Fate Choices
Sean Palecek, PhD
Milton and Maude Shoemaker Professor
Chemical & Biological Engineering
University of Wisconsin-Madison
Tuesday, August 26, 2014 at 9:40 AM
555 Buehler Hall
Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold tremendous promise in tissue engineering and regenerative medicine applications because of their unique combination of two properties, pluripotency and an extremely high proliferative capacity. Theoretically, almost unlimited supplies of cells and tissues could be generated from a single clonal source if we can regulate PSC growth and differentiation. Hurdles facing utilization of PSCs in regenerative medicine include a lack of reliable and efficient methods to differentiate PSCs to desired developmental lineages.
Several critical factors regulate whether a PSC chooses to self-renew or differentiate. Soluble signals bind receptors and stimulate chemical pathways that lead to global changes in gene transcription and cell differentiation state. Likewise, immobilized extracellular matrix cues synergize with soluble signals to control cell signaling and differentiation. Cell-cell communication is also an important consideration in PSC culture; at low cell densities cell growth rates diminish while at high cell densities spontaneous differentiation occurs. Finally, mechanical signals have recently been shown to affect self-renewal and differentiation. Dr. Palecek will discuss examples that illustrate how each of these microenvironmental stimuli can be incorporated in culture systems to expand or differentiate PSCs along desired lineages. He has developed culture systems and engineered cell lines to control developmental pathways that regulate hPSC differentiation toward cardiomyocytes. He has identified canonical Wnt signaling as a key regulator of cardiomyocyte differentiation and designed a protocol that produces high purity cardiomyocytes in a defined, growth factor free system via appropriate temporal presentation of small molecule modulators of Wnt signaling.
Dr. Palecek will also discuss how the temporal presentation of soluble differentiation factors (e.g. retinoic acid and bone morphogenic proteins) and regulation of tyrosine kinase signaling pathways can be utilized to obtain pure populations of stratified epithelial progenitors, which can then differentiate to terminal cells such as epidermal keratinocytes. Dr. Palecek has used these cells to assemble a 3D artificial skin construct and model genetic diseases of the skin. Finally, he will present data illustrating differentiation of pluripotent stem cells to classes of functional vascular endothelial cells, including blood-brain barrier microendothelial cells. These cells are currently being used to construct in vitro models of the blood-brain barrier to predict drug passage to the brain.
Dr. Sean Palecek is the Milton and Maude Shoemaker Professor of Chemical & Biological Engineering at the University of Wisconsin – Madison. Dr. Palecek received a bachelor’s degree in chemical engineering at the University of Delaware. He performed his graduate research with Doug Lauffenburger and Rick Horwitz, earning an M.S. in chemical engineering from the University of Illinois at Urbana-Champaign and a Ph.D. in chemical engineering from MIT. Dr. Palecek performed postdoctoral research in molecular genetics and cell biology at the University of Chicago under the supervision of Steve Kron. His lab studies mechanisms of pathogenesis in fungi, signaling in cancer cells, and developmental fate choices in human pluripotent stem cells. Dr. Palecek’s recent awards include the Cozzarelli Prize of the National Academy of Sciences and the Biotechnology Progress Excellence in Research Publication Award.