WEAVER LAB

UT SOUTHWESTERN MEDICAL CENTER

DEPARTMENT of PHARMACOLOGY

PROTEOLYTIC MECHANISMS in CELL SIGNALING

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Evidence across diverse phyla of metazoans depicts a new landscape for proteolytic factors, such as caspases, as not only effectors but key regulators of many cellular processes. In particular, genetic masking has hitherto limited our ability to observe many so-called "non-canonical" caspase functions that our work has recently brought to light. Now is an exciting time to be part of this rapidly emerging field.

The over-arching theme of the Weaver Lab is to deeply understand how proteolytic factors mediate diverse physiological functions.  Along those lines, we have identified CED-3 caspase working to support a variety of cellular functions ranging from limiting symmetric divisions of a stem-like cell type during cell fate decisions to opposing p38 MAPK stress signaling and downstream gene expression program to promote development. We find that caspases often work with other regulatory pathways to achieve their non-canonical functions.

Current lines of inquiry include: (1) how a given caspase is able to distinguish cell death from cell vigor substrates, (2) how proteolytic factors sculpt gene expression dynamics and (3) what upstream inputs license one proteolytic function over another. Unmasking these mechanisms is critical to understanding diverse disease processes including cancers and degenerative diseases.

To tackle these and other challenging questions, we employ a cross-disciplinary approach including genetics, proteomics, metabolomics and biophysical analyses. The Weaver lab utilizes C. elegans, mammalian cell culture, and biochemical models. Equipped with powerful tools, we are setting out to understand how proteolytic factors execute a potentially vast array of functions.