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Dissecting Single-cell Regulatory States in Tissues and Tumors by Stochastic Profiling
3:30 pm
Location: BME 3.204
Speaker: Kevin Janes, PhD
Associate Professor of Biomedical Engineering
University of Virginia
Host: Dr. Amy Brock
Abstract:
Regulated changes in gene expression underlie many biological processes, but globally profiling cell-to-cell variations in transcriptional regulation is problematic when measuring single cells. We have developed an approach, called stochastic profiling, that applies probability theory to transcriptome-wide measurements of small pools of microdissected cells to identify single-cell regulatory heterogeneities (Nat Methods 7:311-7 [2010]). In the first part of the talk, I will discuss a two-state regulatory circuit that was identified by stochastic profiling (Nat Cell Biol 16:345-56 [2014]). The circuit involves TGFb-family signaling and the junD transcription factor, which are asynchronously activated in 3D breast epithelial cultures to coordinate normal morphogenesis. The circuit also appears to be re-initiated during the early stages of basal-like breast cancer, contributing to the mosaicked expression patterns observed clinically by histology. In the second part, I will talk about a candidate trigger of state switching that is critical for enforcing lobule-like morphogenesis. Interestingly, this TGFb-family ligand is lost by nongenetic mechanisms in single cells and may drive the premalignant-to-invasive transition in triple-negative breast cancer. By quantifying transcriptional programs from human cells microdissected in situ, stochastic profiling identifies regulatory states important for tumorigenesis that would elude methods geared toward single-cell atlases.
Short Bio:
Kevin Janes received his B.S. and B.A. degrees in Biomedical Engineering and Spanish at Johns Hopkins University in 1999. He was a Fulbright Scholar at La Universidad de Santiago de Compostela in Spain before attaining his Ph.D. in Bioengineering at M.I.T. in 2005 under the joint supervision of Douglas Lauffenburger and Michael Yaffe. Dr. Janes completed a postdoctoral fellowship at Harvard Medical School in the Department of Cell Biology with Joan Brugge and began his faculty position at the University of Virginia in 2008. During that time, Dr. Janes was recognized as a Pew Scholar, a Packard Fellow, a Kavli Fellow, and a recipient of the NIH Director's New Innovator Award. He is currently an Associate Professor in the Department of Biomedical Engineering at the University of Virginia, the Vice-Chair of the Tumor Biochemistry and Endocrinology study section at the American Cancer Society, and a member of the Board of Reviewing Editors for Science Signaling.