WEAVER LAB

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.

PEOPLE

DR. BENJAMIN WEAVER

Principal Investigator

DR. YI MIAO WEAVER

Sr. Research Scientist

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DR. WANG YUAN

Post-Doctoral Researcher

DR. HAI WEI

Coming Soon

FRANCISCO CALVA-MORENO

MSTP Graduate Student

RYAN OTTO

Graduate Rotation Student

RESEARCH

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.

DIFFERENTIAL REGULATION

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.

SUBSTRATE RECOGNITION

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.

SELECTED PUBLICATIONS

2018

Tag team: Roles of miRNAs and Proteolytic Regulators in Ensuring Robust Gene Expression Dynamics.

Weaver BP, Han M Trends Genet. 34(1):21-29

2017

Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development.

Weaver BP, Weaver YM, Mitani S, Han M Dev. Cell 41(6):665-673

2016

Time to move the fat.

Weaver BP, Sewell AK, Han M Genes Dev. 30(13):1481-1482

2014
CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression dynamics for robust development in C. elegans.

Weaver BP, Zabinsky R, Weaver YM, Lee ES, Xue D, Han M Elife e04265

ABOUT

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.