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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. Our long-term objective is to illuminate the conserved programs regulating these 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, cell fate, or tuning of stress responsiveness such as in the contexts of cancers, degenerative diseases, and immune disorders. These maladies 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.

PEOPLE

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DR. BENJAMIN WEAVER


Principal Investigator

  

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DR. YI MIAO WEAVER


Sr. Research Scientist

 

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DR. WANG YUAN

Post-Doctoral Researcher


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DR. HAI WEI

Post-Doctoral Researcher

 

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FRANCISCO CALVA MORENO

MSTP Graduate Student

Ph.D. Candidate

Center for Regenerative Science and Medicine Fellowship

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TATIANA
FERREIRA

Graduate School of Biomedical Sciences

 

Rotation Student

Ph.D. Program

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Lab Alumnus
Prerith Arunkumar

2023

STARS Summer Student

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Lab Alumnus
George Jose

 

2023

Green Fellow

Spring Semester

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Lab Alumnus
Irvin Garza

2022

Fall Rotation Student

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Lab Alumnus
Ryan Otto

 

2019

Summer Rotation Student

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WE ARE STILL
RECRUITING!

 

Always happy to hear from folks!

Graduate student applicants: Apply through the umbrella

Ph.D. Program and send Ben an email of interest.

Post-Doc and Technician Applicants: send Ben your letter of interest.

RESEARCH

Current Priorities and Training Environment

The Weaver lab is multidisciplinary and employs state of the art methods in CRISPR mutagenesis, genetics, biochemistry, proteomics, transcriptomics, metabolomics, and advanced imaging to analyze dynamic cellular processes and how they are integrated across distinct cell types within animals. Using C. elegans, mammalian cell culture, and in vitro models, our unified goal is to understand how proteolytic factors regulate critical cell signaling decisions. Trainees will learn cutting-edge methodologies in diverse disciplines. We are actively working on several exciting fronts. Now is an exceptional time to use advanced technologies to examine fundamental biological problems.

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CELL SIGNALING

As an emerging regulatory paradigm, our unpublished findings suggest an array of genes work with caspases to support the viability of cells. Using proteomic, genetic, and cell biology approaches, we are probing how proteolytic factors integrate diverse inputs to mediate cellular outputs. Several grand challenges to solve include: (1) Will these pathways act discretely to regulate independent sets of genes or act broadly coordinating many processes? (2) What developmental and environmental signals activate or inhibit these proteolytic functions? (3) How are these proteolytic functions compartmentalized within a cell to prevent activating cell death? and (4) How does alteration of these pathways contribute to diverse disease processes? Solving these fundamental cellular processes will be broadly illuminating.

STRESS & AGING

Throughout metazoans, p38 MAPKs are critical to initiate stress responses. We recently showed that CED-3 caspase antagonizes a p38 MAPK-dependent pathogen response to promote development.
We are using advanced CRISPR methods combined with omics-based approaches and advanced imaging to understand how this pathway is dynamically regulated throughout animal lifespan. What tissues are important for p38 MAPK regulation within an animal? Beyond innate immunity, does p38 MAPK regulate other targets?

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CELL FATE

We previously demonstrated that a non-canonical caspase function 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.

DIFFERENTIAL REGULATION

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

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SUBSTRATE RECOGNITION

We recently showed that 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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SELECTED PUBLICATIONS

2024

Proteolytic Activation of Fatty Acid Synthase Signals Pan-Stress Resolution

Wei H, Weaver YM, Yang C, Zhang Y, Hu G, Karner CM, Sieber M, DeBerardinis RJ, Weaver BP

Nature Metabolism Ahead of print 2024

Featured in News & Views: Cutting through the Stress

Luis Jasper and Meng Wang Nature Metabolism 2024

2023

Modulating p38 MAPK Signaling by Proteostasis Mechanisms Supports Tissue Integrity during Growth and Aging

Yuan W, Weaver YM, Earnest S, Taylor CA, Cobb MH, Weaver BP

Nature Communications 14, 4543

​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 

Developmental Cell 53(3):  358-369

*Corresponding Author

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

Olya Yarychkivska and Shai Shaham Developmental 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 in Genetics. 34(1):21-29   

*Corresponding Author


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

Developmental Cell 41(6):665-673

*Corresponding Author   

Featured in Partners in Crime

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

2016

Time to move the fat.

Weaver BP*, Sewell AK, Han M

Genes & Development 30(13):1481-1482   

*Corresponding Author

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

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LAB NEWS

January 2024

Congratulations Hai!

Hai's first-author paper now published in Nature Metabolism!  More to come soon!

December 2023

Congratulations Hai!

Hai was honored to receive the...

Alfred & Mabel Gilman Memorial Postdoctoral Excellence in Science Award.

October 2023

Welcome Tatiana!

Joining for a rotation, let's hope Tatiana finds C. elegans as fun as the rest of us do!!

July 2023

Congratulations Wang!

Wang's first-author paper now published at Nature Communications!

June 2023

Welcome Prerith Arunkumar!

Joining us as a rising Senior, Prerith has chosen to embark on his science journey with us as a STARS student this summer.

May 2023

Excellent Meeting!

Ben gave a talk on the lab's exciting recent findings of FASN in stress responses at the Mechanisms of Metabolic Signaling meeting at Cold Spring Harbor.

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 spring 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!

​​

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!

May 2020

Congratulations lab!

Our newest paper out in Dev Cell!  Good start!

​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. 

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 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, and starchy noodles!  Wang's philosophy:  best part is that you can add anything, this dish knows no limits!

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NON-CANONICAL BARBECUE by BEN

Savory homemade marinades with thyme, cumin and bay leaf combined with hickory and cherry smoke for a decadent 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.

Oops

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LAB BOWLING PARTY

Celebrating Francisco passing qualifying exam!!

AGING MEETING 2022

Great colleagues, great science, great weather in Madison...You just can't beat it!

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LAB GOLF PARTY 2023
Celebrating Hai's paper!!

CONTACT

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

 

benjamin.weaver [at] utsouthwestern.edu

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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