The long-term goal of the NOBEL is to develop, optimize and apply innovative technologies to our primary area of focus, which is skeletal muscle. Skeletal muscle is the primary organ system that defines our complex movements and to a degree our life and joy (“joy’s soul lies in the doing” – W. Shakespeare).
MUSCLE STEM CELLS & MUSCLE REGENERATION
Skeletal muscle is a complex tissue that is composed of a constellation of cell types, consumes significant amounts of metabolic energy, grows and adapts its structure based on its environment and uniquely repairs and regenerates when damaged via a pool of stem cells called satellite cells. The NOBEL uses various types of in-vivo and in-vitro models in combination with genomic assays to study the molecular mechanisms of muscle regeneration, after trauma and during aging. We are particularly interested in the role of epigenetic and transcriptional regulation (chromatin, DNAme, RNA, miRNA, lncRNA) of muscle stem cells. Some of our work in this area was profiled by Vivien Marx in Nature Methods.
MINIATURE DEVICES FOR MANIPULATING CELLS
Since the critical sizes of the molecular machines that drive and organize cellular programs are at the scale of micro- and nanofabricated devices (0.3-20,000 nm), these tools offer excellent platforms to study and perturb cellular processes with high precision and throughput. The NOBEL develops tools to illuminate how cells measure and adapt to complex alterations in their constantly changing local micro-environment and is specifically focusing on studying different types of temporal processes such as mechanical changes and cellular communication networks.
CELL FATE PLASTICITY
Manipulation of cell fate is a powerful tool to 1) derive, study and utilize patient-specific stem cells for regenerative medicine and disease modeling and 2) study the delicate interplay between chromatin state and gene expression networks. The NOBEL uses a combination of micro and nanodevices, reporter cell lines, time-lapse microscopy and integrative genomic assays to understand how the flow of information into and out of the epigenome is dynamically initiated, maintained and augmented during the reprogramming process. We have a particular interest in studying how mechanical perturbations influence chromatin-state transitions during reprogramming, how cells reprogram one another and confer transitions into disease and using in-vivo reprogramming technologies for fibrosis reversal.