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WEAVER LAB

UT SOUTHWESTERN MEDICAL CENTER

DEPARTMENT of PHARMACOLOGY

PROTEOLYTIC MECHANISMS in CELL SIGNALING and REGENERATIVE BIOLOGY

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About the Lab:

Regenerative biology holds tremendous promise for overcoming many pathological conditions. We work at the cross-roads of development, aging and stress responses. A major focus of our studies is to understand the nature of gene-environment interactions.

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Major Questions:

How do cells transition between different states?  What factors are required to switch into and out of stress responses or shift from a stem state to a descendant cell fate in development?  How do developmental and stress response pathways impact each other? There remains little understanding of the mechanisms governing these important cellular decisions. 

Impacts to Health:

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. ​

HIGHLIGHTS

Oct 2024
Looking ahead...
Now hiring and more papers coming soon!

Stay tuned for more updates!!

Positions available: Lysosome, Autophagy, Inflammation, Stem Cell, Neuroscience, Stress Responses, Cell Biology, Molecular Biology, and Genetics. Great time to join!!  Reach out to Ben.

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Nature Communications
October 2024
Differential Regulation of Caspases in Stress

Combining promoter mutational analyses, proteomics, genetic screens, and cell biology approaches, we revealed a  factor distinguishing caspase stress responses from cell death. We found that the highly conserved XPD factor is required in C. elegans and human cells to induce expression of stress-responsive caspases without inducing cell death. Our findings demonstrate that the XPD-caspase circuit limits non-genotoxic stress responses to support genotoxic stress responses.

PNAS
October 2024
Exiting Stem Fate

Combining proteomics, transcriptomics, genetic screens, and cell biology approaches, we revealed UBR-5 E3 ligase degrades poly-(A)-binding protein PABP-2. Loss of UBR-5 function globally increases markers of stemness in descendant cells. The balance of UBR-5 and PABP-2 controls exit of stem fate and motility during aging.

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We got the cover of Nature Metabolism!!

January 2024 Issue

See story below on decoding resolution after stress

What an amazing way to kick off the new year!

Special thanks to our collaborators: Ralph, Matt, Courtney and Yuan--thank you all!!

Nature  Metabolism
January 2024
Decoding Resolution after Stress

Combining metabolomics, transcriptomics, genetic screens and cell biology approaches, we revealed CED-3 caspase proteolytically activates the C-terminal fragment of fatty acid synthase (FASN-CTF) to signal stress resolution. This unexpected FASN signaling function is independent of fatty acid synthesis. Activation of the FASN-CTF fragment shuts down innate immunity and UPR gene expression, resolves lipid droplets and switches metabolic programs.

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Nature Communications
July 2023
Maintaining Neurons during Aging

Excellent collaboration with Melanie!

Combining biochemistry with cell biology and mass-spec analyses, we revealed a non-apoptotic caspase function targets p38 MAPK to control signaling output supporting lysosome homeostasis and neuronal integrity during aging when germline is left intact. This paper also revealed that phosphoratio not just absolute of phospho levels modulate net signaling.

Developmental Cell
May 2020
Antagonizing Stress with Development

Combining ribosome profiling with genetic and biochemical analyses, we revealed CED-3 caspase limits pathogen stress response during development by blocking p38 MAPK innate immunity gene expression. This circuit balances development rate with stress responsiveness.

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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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RIA MUKHERJI

Graduate Student

Ph.D. Candidate

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LUKE NUNAMAKER

Research Tech II

 

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Lab Alumni

Francisco Calva Moreno
(MSTP student, defended PhD 2024, returned to Med School)

Tatiana Ferreira (Rotation student 2023)
Prerith Arunkumar (STARS Summer student 2023)
George Jose (Green Fellow 2023)
Irvin Garza (Rotation student 2022)
Ryan Otto (Rotation student 2019)


WE ARE STILL RECRUITING!
Graduate rotations available
Post-doc candidates, email Ben your letter of interests.

RESEARCH

Current Priorities and Training Environment

The Weaver lab is multidisciplinary and combines state of the art methods including genetics, proteomics, transcriptomics, metabolomics, advanced imaging and biophysical analyses. We use C. elegans, mammalian cell culture, and in vitro models. Equipped with powerful tools, we are setting out to understand how proteolytic mechanisms regulate cell state transitions and how these activities are integrated across tissues within animals. Trainees will learn cutting-edge methodologies. We are actively working on several exciting fronts. Now is an exceptional time to join the lab. Take a look at some of the questions we are working actively to address...

STRESS RESPONSES & CELL DYNAMICS

Health relevance: Chronic stress and inflammation are both the drivers and outcomes of many disease processes yet we understand very little as to why these responses remain elevated in some instances and not others.

Basic unknowns:How do cells balance stress responses with developmental needs? How are infections, injuries, and molecular damage detected? How is resolution of stressor sensed? What keeps these responses in check to prevent chronic stress responses?

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STEMNESS & CELL FATE

Health relevance: Diseases ranging from cancer to neurodegeneration have characteristic ages of onset or occurrence in specific tissues suggesting disruption of major regulatory programs ensuring proper cell fate decisions relative to environmental challenge.

Basic unknowns: How are cell fate decisions of stemness versus differentiation regulated? How do we unmask these factors with spatiotemporal resolution? Why do cancer cells live when they should die while neurodegenerative cells die when they should live? Can we alter this balance?

AGING & HEALTHSPAN

Health relevance: Aging-associated diseases strongly correspond to cellular senescence. Strikingly, the aging process seems to be stereotyped within and across animal species. Although we live longer than many other animals, we seem to go through the same stereotypical process of aging--suggesting a predictable breakdown of pattern with respect to relative biological time.

Basic unknowns: If tissues are routinely regenerated throughout life, why do they break down with time? What factors are compromised causing the loss of integrity?  What drives cellular senescence?  Can we alter this clock?

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CELL SIGNALING & METABOLISM

Health relevance: Metabolic disruptions and aberrant cell signaling are associated with the progression of cancers along with many other diseases and infections.

Basic unknowns: How do cells integrate their signaling programs within and across tissues? How are metabolic and gene expression programs coordinated?  What regulates the regulators?

SELECTED PUBLICATIONS

2024

 

Xeroderma Pigmentosum Protein XPD Controls Caspase-Mediated Stress Responses

Wei H, Weaver YM, Weaver BP

Nature Communications 15, 9344 (2024)

UBR-5 and UBE2D Mediate Timely Exit from Stem Fate via Destabilization of Poly(A)-Binding Protein PABP-2 in Cell State Transition

Calva Moreno JF, Jose G, Weaver YM, Weaver BP

Proceedings of the National Academy of Sciences 121(43) e2407561121 (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 6, 113-126 (2024)

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Featured in News & Views: Cutting through the Stress

Luis Jasper and Meng Wang Nature Metabolism 2024

Also featured on the cover!! "FASN cuts stress"  Nature Metabolism Jan 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 (2023)

​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

November 2024

Congratulations Hai!!

Hai got his dream job and is starting his own lab at the Chinese Academy of Sciences in Shanghai!  We are so proud and happy for you!

October 2024

Congratulations Hai!!

Hai's first-author paper now published in Nature Communications!

October 2024

Congratulations Francisco!!

Francisco's first-author paper now published in PNAS!

October 2024

Excellent Visit!

Ben was honored to give a seminar at Washington State University in Spokane and talk about all of the cool stuff going on in the Weaver Lab!

September 2024

Congratulations Weaver Lab!

Ben's R35 MIRA grant got renewed through NIGMS!  Excellent score got funded early!

September 2024

Welcome Luke!

Following undergraduate studies at the University of Wisconsin Madison, Luke joins the Weaver lab as Research Tech!

September 2024

Excellent Meeting!

Ben gave a talk about the lab's exciting recent findings on caspase regulation of stress responses at the 3rd International Non-lethal functions of cell death proteins meeting in Ottawa Canada. Excellent venue and amazing community of colleagues!!

 

August 2024

Welcome Ria!

Following undergraduate studies at the University of Massachusetts Amherst, Ria joins the Weaver lab for graduate studies!

August 2024

Excellent Visit!

Han lab symposium and reunion in Boulder was awesome!!

Honored to be a part of the Han lineage ;-)

July 2024

Congratulations Weaver Lab!

Ben's second grant funded by NIA!  Positions available! 

Reach out to Ben about available topics.

June 2024

Excellent Meeting!

Ben gave a talk about the lab's exciting recent findings on caspase regulation of FASN during stress resolution at the Metabolism, Aging, Pathogenesis, and Stress in C. elegans meeting in Madison Wisconsin.

June 2024

Fingers Crossed!

2 more papers in revision at the same time!

May 2024

Congratulations Dr. Calva Moreno!

Francisco successfully defended his PhD!

Heading back to Med School to complete his MD degree.

March 2024

Excellent Visit!

Ben was honored to give a seminar at the OHRI in Ottawa Canada and talk about all of the cool stuff going on in the Weaver Lab!

February 2024

Congratulations Hai!

Hai's paper made the January cover of Nature Metabolism!

January 2024

Congratulations Hai!

Hai's first-author paper now published in Nature Metabolism!

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!

August 2023

Congratulations Wang!

Wang's paper was featured at Nature Communications in the collection

"From molecules and cells to organisms"

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!

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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!

May 2020

Congratulations lab!

Our paper with Yi and Wang is 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 Early Stage Investigator 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

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Min hanging out with the Weaver lab on his May 2022 visit to UT Southwestern!!!
Kind of like worlds colliding when your post-doc mentor meets your lab.  Is "science grandpa" a thing?  ;-)

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May 2024 Francisco defends his PhD!!!
Congratulations Dr. Calva Moreno!! 
We all knew you could do it!

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Party food!! 
 

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More party food!!
 

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Physiology Retreat 2022
Dallas Arboretum

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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!!

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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!!
What? That is a smile. Maybe just stunned his paper got accepted and got the cover!!  ;-)

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Cold Spring Harbor May 2023
Mechanisms of Metabolic Signaling meeting was awesome!! Great colleagues and venue!

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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