UT SOUTHWESTERN MEDICAL CENTER
DEPARTMENT of PHARMACOLOGY
-Understanding Roles of Caspases in Cell Vigor-
Evidence across diverse phyla of metazoans depicts a new landscape for caspases in cellular processes. Genetic masking has hitherto limited our ability to observe many so-called "non-canonical" caspase functions. Right now is an exciting time to be part of this rapidly emerging field. The over-arching theme of the Weaver lab is to understand: (1) how caspases with both cell death and cell vigor functions are differentially regulated and (2) how a given caspase is able to distinguish cell death from cell vigor substrates. To tackle these challenging questions, we employ a cross-disciplinary approach including genetics, proteomics and biophysical analyses. The Weaver lab utilizes C. elegans, mammalian cell culture, and in vitro models. Equipped with a diverse array of tools, we are setting out to understand how caspases execute a potentially vast array of functions.
DR. BENJAMIN WEAVER
DR. YI MIAO WEAVER
Sr. Research Scientist
DR. WANG YUAN
DR. HAI WEI
MSTP Graduate Student
Graduate Rotation Student
Non-Canonical Caspase Functions
GENE EXPRESSION DYNAMICS
We recently showed a key role for CED-3 caspase in destabilizing the LIN-28 pluripotency factor. This proteolytic inactivation of a key stem-promoting factor allows cell fate specification of seam cells, an epidermal stem-like cell type. Other labs have shown analogous roles for caspases in mammalian stem cells. We want to know how broadly caspases act in gene expression dynamics. We are using a big data approach including genomics, proteomics, and translatomics to address this question.
Across nematodes, flies, and mammals, classic cell death caspases have been found with critical non-apoptotic functions. Thus, non-apoptotic functions of cell death caspases are not peculiar to any metazoan branch but rather the rule for caspases. We want to know how a given caspase with both cell death and cell vigor functions is differentially regulated. We are using genetic and biochemical methods to address this question.
We recently showed that the CED-3 caspase required a UBR-type E3 ubiquitin ligase to efficiently cleave LIN-28 in vivo. We further showed that the caspase and E3 ligase may form a complex. We want to know how a caspase with cell death and cell vigor activities differentially recognizes substrates. We are using biochemical and biophysical methods to address this question.
Tag team: Roles of miRNAs and Proteolytic Regulators in Ensuring Robust Gene Expression Dynamics.
Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development.
Time to move the fat.
CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression dynamics for robust development in C. elegans.
While working in the Han lab at CU Boulder, we discovered that CED-3 caspase works in parallel to the miRISC pathway to help limit supernumerary cell divisions of an epidermal stem-like cell type in C. elegans. We also found that this caspase required a UBR-type E3 ubiquitin ligase from the Arg/N-end rule to efficiently proteolytically cleave the non-apoptotic target LIN-28 in vivo. This non-canonical caspase function was unmasked by genetic methods and elaborated by biochemical studies.
The Weaver lab was established in 2018 in the Department of Pharmacology at UT Southwestern Medical Center. Our central goal is to identify the unifying principles underlying the regulation of non-apoptotic, cell vigor functions of caspases. We consider ourselves adventurous biologists. We are not tied to any one scientific discipline and therefore use whatever method is best to address a given biological question. If you're interested in joining a dynamic and energetic lab, please contact us.
This website reflects only the views of the author and is not a publication of UT Southwestern, which bears no responsibility for its content.
UT Southwestern Medical Center
6001 Forest Park Rd
Dallas, TX 75390
benjamin.weaver [at] utsouthwestern.edu