Muir Lab

Lymph node environment drives FSP1 targetability in metastasizing melanoma - Nature Targeting FSP1 in lymph nodes has considerable potential for blocking melanoma progression.

Melanoma cells that spread to lymph nodes depend on FSP1 to survive, revealing a new metabolic vulnerability. New study in Nature by @mariopalma.bsky.social @ubellackerlab.bsky.social and colleagues shows that blocking FSP1 triggers ferroptosis and suppresses tumor growth in lymph node metastases.

FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis - Nature Cell Biology Lange et al. identify a lipid droplet quality control pathway in which FSP1 safeguards stored neutral lipids from lipid peroxidation, thereby preventing the induction of ferroptosis.

Excited to share our study out in @natcellbio.nature.com! Led by @mikelangelipid.bsky.social, we identify the first #LipidDroplet lipid quality control pathway: LD-localized FSP1 protects stored lipids from oxidative damage and prevents LD-initiated #ferroptosis.
www.nature.com/articles/s41...

Our work detailing the metabolic roles of serum for cancer cell proliferation is now out at JBC, @asbmbjournals.bsky.social!

Congrats to Oliver and Eric and many thanks to the editor and reviewers for a thoughtful and efficient review process.

See here:
www.sciencedirect.com/science/arti...

Repost! Please apply by October 15th for full consideration.

Just out in @science.org: Together with the lab of @wilhelmpalm.bsky.social, we used sequential in-vitro/in-vivo CRISPR screens to decipher metabolic adaptations in tumors. We find that acidosis is a dominant factor that shapes energy metabolism and stress resilience. www.science.org/doi/10.1126/...

A microneedle device for rapid dermal interstitial fluid sampling A device collects enough skin interstitial fluid for omics studies in just five minutes.

A microneedle device for rapid dermal interstitial fluid sampling @stanforduniversity.bsky.social 🇺🇲 www.science.org/doi/10.1126/...

Thanks Natalie! @cssheehan.bsky.social responsible for all monthy python jokes :)

Looking forward to your feedback as we continue to work this problem!

Super great to work with James LaBelle’s lab on this project! And thanks to everyone involved in the study: Kay Macleod, @cjhphd.bsky.social, Alica Beutel,
@leahziolkowski.bsky.social, Mumina Sadullozoda, @patrickjonker.bsky.social, Darby Agovino, Grace Croley, @guillaumecognet.bsky.social.

(3) Fortress model is insufficient to explain drug resistance in pancreatic. Tolerance (tis but a scratch) also critical to drug resistance. Will need effort on overcoming tolerance in addition to improving drug delivery to improve treatment outcomes.

(2) Simple changes to culture models, like growing cells in the right nutrients, keeps cells in in vivo relevant states that we care about, like being drug resistant. Important for getting models that are predictive for things like drug discovery and for precision medicine.

Implications: (1) Using standard culture models to do things like drug screens, will make apoptosis inducers look great, even though they will have limited efficacy in vivo. Could be fruitful to look at other treatment modalities that kill cells non-apoptotically.

How does the TME/TIFM cause drug resistance? Apoptotic priming gets turn wayyyyy down. So, cells just don’t die from chemo or targeted therapies despite on target action. Call this the “tis but a scratch model” of drug resistance.

Interestingly, we recently made a new cell culture model (TIFM) where PDAC cells are grown in the nutrients they would see IRL (elifesciences.org/articles/81289). TIFM-derived PDAC cell lines maintain the therapy resistant state! So, have a tractable model to study this state now.

Why haven’t we seen this before? Well, if you keep the cancer cells in culture, after a few weeks, the cells become drug sensitive again! So, the tumor imprints a drug-resistant state that cell culture can’t maintain. Critical for chemo and targeted therapy resistance.

So, how else do tumors become drug resistant? @cssheehan.bsky.social cial found even if you take pancreatic cancer cells out of the tumor and look at drug response ex vivo, the cells are drug resistant. Clearly, something else going on beyond the fortress model.

But fortress model can't explain recent findings that tumors are still resistant even if you work to get the drugs in there (pubmed.ncbi.nlm.nih.gov/32030361/) and new mass spec imaging data (pubmed.ncbi.nlm.nih.gov/35005896/) that shows drugs getting into tumors.

Know that pancreatic cancer cells are not inherently drug resistant but that tumors are. What about tumors makes them drug resistant? Longstanding hypothesis is that fibrosis limits drug delivery to tumors making them resistant. We call this the “fortress model”.

Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer Cytotoxic chemotherapy remains the standard-of-care treatment for patients with pancreatic ductal adenocarcinoma (PDAC). However, chemotherapy only has modest effects at improving patient survival due...

Super excited to share our new preprint from @cssheehan.bsky.social on how the tumor microenvironment causes drug resistance in pancreatic cancer: www.biorxiv.org/content/10.1...

An alternative route for β-hydroxybutyrate metabolism supports cytosolic acetyl-CoA synthesis in cancer cells - Nature Metabolism Kaluba, Rogers et al. show that in cancer cells that can metabolize ketones, they may reroute them to produce cytosolic acetyl-CoA and support tumour growth.

An alternative route for β-hydroxybutyrate metabolism supports cytosolic acetyl-CoA synthesis in cancer cells www.nature.com/articles/s42...

I am thrilled to share that I have received an ERC Starting Grant for our project SpaceMet!
I am grateful for the ERC’s commitment to ambitious early-stage research and to KU Leuven for their support!
Stay tuned, new postdoc positions coming soon!I @erc.europa.eu @kuleuvenuniversity.bsky.social

Hot off the presses! Was an honor to team up with Scott Dixon @stanforduniversity.bsky.social on this Nature Cancer review. We reflect on hurdles that have slowed translation of ferroptosis-directed therapies and share ideas on what it will take to bring these therapies to the clinic. rdcu.be/eBbqV

Super cool and excited to read!

Riboflavin metabolism shapes FSP1-driven ferroptosis resistance Membrane protection against oxidative insults is achieved by the concerted action of glutathione peroxidase 4 (GPX4) and endogenous lipophilic antioxidants such as ubiquinone and vitamin E. Deficienci...

🚨Preprint alert 🚨

We identify riboflavin (vitamin B₂) as a key modulator of ferroptosis sensitivity via stabilizing FSP1 & recycling lipid-soluble antioxidants.

www.biorxiv.org/content/10.1....

pls check @olzmannlab.bsky.social

www.biorxiv.org/content/10.1...

#ferroptosis #FSP1 #antioxidants

Join me in Boston October 6th for a 1-day conference on #mappingbiology to transform #cancertherapeutics. Register by September 25th to benefit from the complimentary (free) admission! Topics, speakers, and talk opportunities here: abcam.me/mappingbiolo...
@abcamofficial.bsky.social

Open Rank, Tenure Track Position – Metabolic Physiology - Salt Lake City, Utah job with University of Utah | 674355 The Department of Nutrition and Integrated Physiology (NUIP) at the University of Utah seeks a Tenure Track faculty member at the rank of Assistant...

We have an Open Rank tenure-track faculty position in the Department of Nutrition & Integrative Physiology! Looking for a new colleague interested in making the University of Utah their new home to build a metabolic research program. Please share! @uofunuip.bsky.social

Fantastic meeting 🤩🤩
thank you @olzmannlab.bsky.social and Scott Dixon for the organisation and for all the colleagues and trainees that showed up and made ut such a great event!
#ferroptosis #faseb #Ros

Super cool! Congratulations!

The EAAT1 aspartate/glutamate transporter is dispensable for acute myeloid leukemia cell growth and response to therapy https://www.biorxiv.org/content/10.1101/2025.07.13.664609v1

2025 Midwest Metabolism Meeting Join us for 2025 Midwest Metabolism Meeting at Van Andel Institute Stay informed about exciting upcoming events and activities.

1/ If you are in the Midwest and ❤️ metabolism, take note!

This year’s Midwest Metabolism meeting will be held jointly with the Translational Research in Mitochondrial Metabolism in Aging and Disease (TRiMAD) conference.

www.vai.org/event/2025-m...