Andrew Holle
Assistant Professor
Mechanobiology Institute
National University of Singapore

*In-person-only event!

ABSTRACT
Cells migrating through tissues routinely encounter physical spaces smaller than themselves, requiring substantial deformation of both the cell and nucleus. Our laboratory is interested in how these mechanical experiences influence cell behavior, state, and fate across cancer, stem cell, and developmental systems. Using engineered microchannels, we have shown that adult stem cells can navigate highly confined spaces and that this process is accompanied by changes in differentiation-associated transcription factors and epigenetic state. We have also developed high-throughput porous confinement platforms that allow migrated cell populations to be isolated and subjected to downstream molecular profiling, providing a way to connect physical behavior with transcriptional and epigenomic changes at scale. More recently, we have extended these questions into development using primordial germ cells, which undergo striking nuclear deformation as they migrate through narrow interstitial spaces in vivo. Together, this work supports a broader view of confinement not simply as a barrier to migration, but as a potentially instructive mechanical signal that helps shape cellular identity and maturation.
 
BIO
Andrew Holle received a Bachelor of Science, Engineering (B.S.E) from Arizona State University, where he worked in labs of Christine Pauken and Deirdre Meldrum. He then received his Ph.D. at the University of California, San Diego, where he worked in Adam Engler’s Stem Cell Biology and Bioengineering group. There, he identified the mechanosensitive role of the focal adhesion protein vinculin in substrate stiffness-induced stem cell differentiation. Looking to explore the commonalities between stem cell and cancer mechanobiology, he then joined Prof. Joachim Spatz’s Cellular Biophysics group at the Max Planck Institute for Medical Research (Stuttgart, Germany). There, he used photolithography and microfluidics to build microchannel assays to better characterize cancer cell invasion and migration in confinement. His Confinement Mechanobiology lab at the Mechanobiology Institute and in the NUS Biomedical Engineering department focuses on the role of confinement in mechanobiology, with an emphasis on novel strategies for controlling stem cell differentiation. 

Jennifer Curtis - faculty host