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WEAVER LAB

UT SOUTHWESTERN MEDICAL CENTER

DEPARTMENT of PHARMACOLOGY


PROTEOLYTIC MECHANISMS in CELL SIGNALING

Life and death decisions are of paramount importance to all cells. Paradoxically, emerging evidence depicts a new regulatory landscape in metazoans where the same proteolytic machinery supports both outcomes of life and death. This duality suggests an unprecedented network of factors differentially regulating these activities for which we have no understanding. ​Our lab is working to unmask these ancient pathways.

The over-arching theme of the Weaver Lab is to deeply interrogate how proteolytic mechanisms mediate seemingly contradictory physiological functions. Current lines of inquiry include: (1) how caspases and other proteolytic factors distinguish distinct substrates, (2) how proteolytic factors sculpt gene expression dynamics and (3) what upstream inputs license one proteolytic activity over another. We aim to illuminate the conserved programs regulating fundamental cellular processes.

Deciphering these novel regulatory paradigms is essential to understanding a broad spectrum of disease processes. Pathological outcomes reflect critical tradeoffs of cell turnover or stress responsiveness such as in the contexts of cancers, degenerative diseases, and immune disorders. These pathologies underscore the importance of cells to sense their internal and external environments and respond accordingly. How cells and tissues integrate diverse inputs during development and aging remain wide open areas of research. Our goal is to resolve these long-standing mysteries. ​

To tackle these challenging questions, we employ a multi-disciplinary approach combining genetics, proteomics, transcriptomics, metabolomics, advanced imaging and biophysical analyses. The Weaver lab utilizes C. elegans, mammalian cell culture, and in vitro models. Equipped with powerful tools, we are setting out to understand how proteolytic mechanisms regulate basic biological processes and how these activities are integrated across tissues within animals.

Weaver Lab: Overview

PEOPLE

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DR. BENJAMIN WEAVER


Principal Investigator

  

Assistant Professor &
Virginia Murchison Linthicum Scholar in Medical Research

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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


Caspases and p38 MAPKs in development and aging

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DR. HAI WEI

Post-Doctoral Researcher

 

Caspases in stress responses

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FRANCISCO CALVA MORENO

MSTP Graduate Student

Ph.D. Candidate

Center for Regenerative Science and Medicine Fellowship

UBR E3 ligases in development and disease

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GEORGE JOSE

UT Dallas

Undergraduate Student


Green Fellow

Physical interactors of UBR E3 ligases in development

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WEAVER LAB

Bowling

2022 Lab Celebration

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WE ARE STILL RECRUITING!!


Grad Student applicants: Apply through the umbrella program and send Ben an email.

Post-Doc and Technician applicants: email Ben with your letter of interest.

Weaver Lab: Lab Members

RESEARCH

Current Priorities and Training Environment

The Weaver lab is interdisciplinary and employs state of the art CRISPR mutagenesis, genetic, biochemical, proteomic, transcriptomic, metabolomic, and imaging methods to analyze dynamic processes in development, aging and stress responses. Using C elegans, mammalian cell culture, and in vitro models, our goal is to understand how proteolytic factors regulate critical cell signaling decisions. Understanding these mechanisms is crucial to diverse disease etiologies including cancers, degenerative diseases, and developmental disorders.  Our lab has exceptional facilities for advanced microscopy, cell culture, and  molecular biology. Trainees joining the Weaver lab will learn cutting-edge methodologies in diverse disciplines.  We have an array of ongoing studies with several areas of emphasis indicated below. Trainees will have distinct projects developed with substantial mentoring.

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CELL SIGNALING

We unmasked an array of genes working with caspase to support viability. Using proteomic, genetic, and cell biological approaches, we are probing how proteolytic factors integrate cell signaling.

GENE EXPRESSION DYNAMICS

We recently showed CED-3 caspase and PMK-1 p38 MAPK balancing stress-responsive and developmental functions. We are using a big data approach including genomics, proteomics, and translatomics to understand how broadly caspases and p38 MAPKs act in gene expression dynamics.

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CELL FATE

Using genetic, biochemical, and genomic approaches we demonstrated a non-canonical caspase function working in parallel to the miRISC pathway is necessary for temporal cell fate patterning to limit symmetric cell divisions at a critical developmental window. We are expanding these studies to understand the roles of other proteolytic factors in cell fate decisions.

STRESS & AGING

Throughout metazoans, p38 MAPKs have stress response functions. We recently showed how CED-3 caspase blocks activation of a p38 MAPK-dependent pathogen response in development. We are using advanced CRISPR methods combined with omic approaches and advanced cell imaging to understand how developmental and stress-responsive states are dynamically regulated.

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C elegans

DIFFERENTIAL REGULATION

Across nematodes, flies, and mammals, classic cell death caspases have been found with critical non-canonical functions supporting cell vigor.  We are using genetic and biochemical methods to understand how a given caspase with both cell death and cell vigor functions is differentially regulated.

SUBSTRATE RECOGNITION

We recently showed that the CED-3 caspase requires a UBR-type E3 ubiquitin ligase to efficiently cleave and degrade LIN-28 in vivo. We further showed that the caspase and E3 ligase physically interact. We are using biochemical and biophysical methods to understand how proteolytic factors recognize distinct substrates.

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Weaver Lab: Research
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SELECTED PUBLICATIONS

2022

Balancing p38 MAPK Signaling with Proteostasis Mechanisms Supports Tissue Integrity during Aging in C. elegans

Yuan W, Weaver YM, Earnest S, Taylor CA, Cobb MH, Weaver BP bioRxiv July 12, 2022


​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

Weaver Lab: Publications
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LAB NEWS

May 2023

Congratulations Ben!

Ben is honored to join the 2023 TAMEST meeting as the protege of Dr. David Mangelsdorf Professor and Chair of Pharmacology.

February 2023

Congratulations Yi! 

Yi was honored to receive the Gilman Special Opportunities in Pharmacology Award.

January 2023

Welcome George Jose! 

Joining us as an undergraduate from UT Dallas, George has received a presitigious Green Fellowship and has chosen to spend the semester with us for undergraduate research.

November 2022

Congratulations Ben!

Ben was thrilled to deliver the Alvin Sarachek Research Seminar at his alma mater in the Department of Biological Sciences of Wichita State University.

September 2022

Excellent Meeting!

Ben gave a talk about the lab's exciting recent findings on caspase regulation of p38 MAPK signaling controlling neuroprotection during aging at the 2nd international Non-Lethal Roles of Cell Death Proteins meeting in Galway Ireland.

September 2022

Congratualtions Francisco!

Francisco was awarded a prestigious graduate fellowship from the Hamon Center for Regenerative Science and Medicine!

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July 2022

Excellent Meeting!

Ben gave a talk about the lab's exciting recent findings on caspase regulation of p38 MAPK signaling controlling neuroprotection during aging at the Metabolism, Aging, Pathogenesis, and Stress in C. elegans meeting in Madison Wisconsin.

​​July 2022

Congratulations Wang! 

Wang's first author paper posted on bioRxiv

https://doi.org/10.1101/2022.07.12.499791

June 2022

Congratulations Ben!

Ben was honored to join the 2022 TAMEST meeting as the protege of Dr. Melanie Cobb, Professor of Pharmacology.

June 2022

Awesome Jobs Hai and Wang!

Hai gave a terrific talk and Wang gave an exceptional poster at the Physiology retreat!

April 2022

Awesome Job Francisco!

Francisco gave a terrific talk at the CMB graduate symposium!

April 2022

Move is Done!

Everyone pitched in and we finally moved into our newly-renovated space.  Awesome microscopy and tissue culture facilities.

​​May 2021

Congratulations Francisco!

Francisco passed his qualifying exams!

March 2021

Congratulations Wang!

Wang wins the Spring Pretty Gel Competition!

​February 2020

Welcome Dr. Hai Wei! 

After graduate school in Munich, Hai joins the lab for post-doctoral studies.

November 2019

Welcome Francisco Calva Moreno!

Following undergraduate studies in Philly, Francisco joins the lab for graduate studies.

September 2019

Excellent Meeting!

Ben gave a talk about the lab's recent exciting findings on caspase-mediated regulation of pathogen response during development at the 1st international Non-Apoptotic Roles of Cell Death Proteins meeting in Rehovot Israel.

July 2019

Congratulations Weaver Lab!

Ben's MIRA grant funded through NIGMS!

May 2019

Welcome Dr. Wang Yuan! 

After training in Iowa, Wang joins the lab for post-doctoral studies.

April 2019

Congratulations Weaver Lab!

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.

Post-Doc Years

Thank You Min and All of the Han Lab!

Ben and Yi worked in Min Han's HHMI lab at CU Boulder where we discovered a non-canonical function for CED-3 caspase and UBR-1 E3 ligase in cell fate determination. 

Weaver Lab: About

GALLERY

Weaver Lab: Photo Gallery

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 from around the globe.  Here are a few glimpses of having some fun experimenting outside the lab.

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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!

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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!

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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!

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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?

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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.

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Hai joins the lab, New Years 2020!!!

Sorry Wang and Francisco...

We forgot to take pictures of your celebrations.

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Weaver Lab: News & Resources

CONTACT

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


benjamin.weaver [at] utsouthwestern.edu

Just Started on Twitter:  @WeaverScience

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

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Weaver Lab: Contact
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