UT Southwestern Medical Center
WEAVER LAB
UT SOUTHWESTERN MEDICAL CENTER
DEPARTMENT of PHARMACOLOGY
PROTEOLYTIC MECHANISMS in CELL SIGNALING and REGENERATIVE BIOLOGY
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.
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.
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.
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.
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.
PEOPLE
DR. BENJAMIN WEAVER
Principal Investigator
DR. YI MIAO WEAVER
Sr. Research Scientist
DR. WANG YUAN
Post-Doctoral Researcher
DR. HAI WEI
Post-Doctoral Researcher
RIA MUKHERJI
Graduate Student
Ph.D. Candidate
LUKE NUNAMAKER
Research Tech II
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?
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?
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)
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
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
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!
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
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? ;-)
May 2024 Francisco defends his PhD!!!
Congratulations Dr. Calva Moreno!!
We all knew you could do it!
Party food!!
More party food!!
Physiology Retreat 2022
Dallas Arboretum
Hai joins the lab, NEW YEARS 2020!!!
Sorry Wang and Francisco...We forgot to take pictures of your celebrations. Oops
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!
LAB GOLF PARTY 2023
Celebrating Hai's paper!!
What? That is a smile. Maybe just stunned his paper got accepted and got the cover!! ;-)
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
