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WEAVER LAB

UT SOUTHWESTERN MEDICAL CENTER

DEPARTMENT of PHARMACOLOGY


PROTEOLYTIC MECHANISMS in Cell Fate, Signaling and Gene Expression Dynamics

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. Right 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.


To tackle these and other challenging questions, we employ a cross-disciplinary approach including genetics, proteomics 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.

 

PEOPLE

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DR. BENJAMIN WEAVER

Principal Investigator

   

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DR. YI MIAO WEAVER

Sr. Research Scientist

Structure function studies of proteolytic factors

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DR. WANG YUAN

Post-Doctoral Researcher

Roles of caspases and p38 MAPK in development

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DR. HAI WEI

Post-Doctoral Researcher

Caspases in stress responses

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FRANCISCO CALVA-MORENO

MSTP Graduate Student

UBR E3 ligases in development and disease

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YOU?


If you're interested in joining an energetic and dynamic lab, please contact us.

 

RESEARCH

Current Priorities

C elegans
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GENE EXPRESSION DYNAMICS

We recently showed CED-3 caspase and PMK-1 p38 MAPK inversely regulate the expression of over 300 genes to balance stress-responsive and developmental functions. We want to know how broadly caspases act in gene expression dynamics and how they achieve these outcomes. We are using a big data approach including genomics, proteomics, and translatomics to address these questions.

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 and degrade LIN-28 in vivo. We further showed that the caspase and E3 ligase may form a complex. We want to know how proteolytic factors differentially recognizes substrates. We are using biochemical and biophysical methods to address this question.

 

SELECTED PUBLICATIONS


2020

Non-Canonical Caspase Activity Antagonizes p38 MAPK Stress-Priming Function to Support Development

Weaver BP, Weaver YM, Omi S, Yuan W, Ewbank JE, Han M  Dev Cell 53(3):  358-369

Featured in Development or Disease: Caspases Balance Growth and Immunity in C. elegans

Olya Yarychkivska and Shai Shaham Dev Cell 53(3): 259-260

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   

Featured in Partners in Crime

Barbara Conradt Dev Cell 41(6):  573-574

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

Featured in Development: Cell Death Machinery Makes Life More Robust

Cristina Aguirre-Chen and Christopher M Hammell eLife 3:e05816

Also featured in For Caspases, An Escape from Death

Beverly A Purnell Science 347(6218): 142-143


   

 

UPDATES

May 2020

Our paper in Dev Cell shows CED-3 Caspase blocks p38 MAPK stress-priming function.

February 2020

Dr. Hai Wei joins the lab for post-doctoral studies!

November 2019

Francisco Calva-Moreno joins the lab for graduate studies!

July 2019

Ben's MIRA grant funded through NIGMS!

May 2019

Dr. Wang Yuan joins the lab for post-doctoral studies!

April 2019

Ben's Welch Foundation grant funded!

September 2018

Weaver Lab Established!

Ben and Yi get to work in the Department of Pharmacology at UT Southwestern Medical Center. Our central goals are to unravel how proteolytic factors impact diverse physiological outcomes and how these divergent functions are regulated. 

Post-Doc Years

While working in Min Han's HHMI lab at CU Boulder, we discovered that CED-3 caspase works in parallel to the miRISC pathway to 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

 

GALLERY

Worm Void
Sometimes It Works
Glow On!
Choices, Choices
Gel Biologists
Real Grinder
Stretching Out
Phenotypical
Columns of Data
Making Mutants
Small but Fast
Flying By
Got It!
Stacks and Stacks
Happy PI
Roundup
Reckon So
Plasticity

 

FUN

Food for Thought

Not too surprisingly, biochemistry was born out of early efforts to perfect the enzymology and chemistry behind the fermentation of grains, fruits and milk to generate the varieties of dough, beer, wine and cheese that we know today.  Here are a few glimpses of how we celebrate--as well as have some fun experimenting outside the lab.

TRADITIONAL PIE of CHINA by HAI

Power-packed gems filled with pork and cabbage. Seasoned with salt, soy sauce, oil, garlic, ginger, and green onion.  Hai’s pro-tip:  Make the outside bun with fermented dough.  After lightly frying, pop these little party favorites into the oven for a crispy baked finish you won’t soon forget!

BEEF RAMEN NOODLES by YI

Fusion of ramen noodles seasoned lightly with onion and parsley for a hearty combo.  Yi’s top-shelf ingredients…Tie this simple masterpiece together with Napa cabbage boiled in a soy-based broth. Add wood-smoked beef slices on top for a simple but super-delicious meal!

FAJITAS by FRANCISCO

Visually stunning arrangement of fajitas served with guacamole, beans, pico de galla and rice. 

That’s not all!  Francisco threw in a loaf of baked banana bread for a super-satisfying finish!

HOT POT by WANG

Traditional Chinese sensation that begins with a spicy soup stock and an assortment of meats, veggies, starchy noodles and you’re ready to roll!  Wang's philosophy:  best part is that you can add anything, this dish knows no limits!  What more could you ask for?

NON-CANONICAL BARBECUE by BEN

Savory homemade marinades with thyme, cumin and bay leaf combined with hickory and cherry wood smoke for a decadent, savory flavor.  How to plate?   Ben likes to serve up his BBQ with grilled asparagus and homemade potato salad.

Hai joins the lab, New Years 2020!!!

Sorry Wang and Francisco...

We forgot to take pictures of your celebrations.

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CONTACT

Interested in joining?  We would love to hear from you.

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
Pharmacology
6001 Forest Park Rd
Dallas, TX 75390
USA

benjamin.weaver [at] utsouthwestern.edu

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©2018 by Weaver Lab