Rich Possemato

Functionally dominant hotspot mutations of mitochondrial ribosomal RNA genes in cancer Nature Genetics - Analysis of 14,106 tumor genomes highlights recurrent mutations in mitochondrial ribosomal RNA encoded within the mitochondrial genome. Mutations occur at hotspot positions and...

Excited to share our latest work in collaboration with the @edreznik.bsky.social lab @mskcancercenter.bsky.social, where we describe functionally dominant mitochondrial DNA mutations in patient tumors. So, what is functional dominance in mitochondrial genetics, I hear you ask?

rdcu.be/eN1jm

Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis Khan et al. apply machine learning to identify substrates of UNC93A, SLC45A4, and SLC25A45. Biochemical assays and in vivo metabolite tracing establish SLC25A45 as a key mediator of mitochondrial impo...

Excited to share our work on discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine biosynthesis. @cp-cellmetabolism.bsky.social www.cell.com/cell-metabol...

GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling During nutrient deprivation, activation of the protein kinase GCN2 regulates cell survival and metabolic homeostasis. In addition to amino acid stress, GCN2 is activated by a variety of cellular stres...

Beautiful reconstitution of amino acid stress-dependent ISR activation by my @harvardcellbio.bsky.social colleagues presenting a unifying mechanism for GCN2 activation, which requires ribosome collisions and is enhanced by cognate uncharged tRNA in the A site! www.science.org/doi/10.1126/...

Basal cell of origin resolves neuroendocrine–tuft lineage plasticity in cancer Nature - Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining...

Super pleased to announce our latest suggesting the cell of origin for #SCLC is most likely the basal cell @nature.com, not the accepted neuroendocrine cell. Implications for the earliest events in cancer, & providing new models of tuft-like cancer.
rdcu.be/eGUtj

Rewiring of cortical glucose metabolism fuels human brain cancer growth - Nature The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources s...

New discovery from our team defining how human brain cancers rewire the metabolism of the normal brain published this week @nature.com and led by stellar postdoc Drew Scott (comentored by @lyssiotislab.bsky.social and currently on job market with a K99/R00). www.nature.com/articles/s41...

PEX39 facilitates the peroxisomal import of PTS2-containing proteins - Nature Cell Biology Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the im...

Our work on new paradigm in peroxisome biogenesis and PEX39 (1st human peroxisomal biogenesis protein (peroxin/PEX) found in > 20 yr) is out in @natcellbio.nature.com! Equal collab w/Tony Rodrigues (Jorge Azevedo lab), @dwendscheck.bsky.social (Bettina Warscheid lab)

www.nature.com/articles/s41...

Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry - Nature APC/C activity is transiently inhibited to generate a pulse of glycolysis that is required for mammalian cell cycle entry.

www.nature.com/articles/s41...

Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry

Conservation and divergence of metabolic phenotypes between patient tumours and matched xenografts - Nature Metabolism Rao and Cai et al. perform a detailed metabolic comparison between primary tumours from patients and their matching xenografts, which identify conserved as well as divergent metabolic patterns.

1/Patient-derived xenografts (PDXs) are used in preclinical testing of cancer therapies, including metabolic therapies. We determined which metabolic properties are retained, and which are lost, when melanomas from patients are implanted and passaged as PDXs in mice.
www.nature.com/articles/s42...

Director Vought: We write to ask you to fully implement the Fiscal Year (FY) 2025 Full-Year Continuing Appropriations and Extensions Act, including funds appropriated for the National Institutes of Health (NIH). The continuing resolution supp011s NIH initiatives across a range of critical research areas­cancer, cardiovascular disease, rare pediatric disorders, and more. These vital efforts are not only necessary to Make America Healthy Again, but also have a direct impact on American families, biomedical innovation, our economy, and competing with Communist China. We are concerned by the slow disbursement rate of FY25 NIH funds, as it risks undermining critical research and the thousands of American jobs it supports. Suspension of these appropriated funds - whether formally withheld or functionally delayed - could threaten Americans' ability to access better treatments and limit our nation's leadership in biomedical science. It also risks inadve11ently severing ongoing NIH-funded research prior to actionable results. We share your commitment to ensuring NIH funds are used responsibly and not diverted to ideological or unaccountable programs. We are confident Secretary Kennedy and Director Bhattacharya are well positioned to uphold gold standard research by ensuring that NIH awards are grounded in transparency, scientific merit, and a clear alignment with national interests. Our shared goal is to restore public trust in the NIH precisely because its work is focused on results, accountability, and real-world impact. Withholding or suspending these funds would jeopardize that trust and hinder progress on critical health challenges facing our nation. Ultimately, this is about finding cures and seeing them through to fruition. We respectfully request that you ensure the timely release of all FY25 NIH appropriations in accordance with congressional intent. Doing so will ensure continued momentum in curing disease, supp011ing American innovation, and delivering result…

Sincerely, Katie Boyd Britt John Boozman Shelly Moore Capito Bill Cassidy Susan Collins Lindsey O. Graham David H. McCormick Mitch McConnel Jerry Moran Lisa Murkowski Thom Tillis Todd Young Dan Sullivan Tim Scott

From @aaas.org check-in with Sudip Parikh: a letter by 14 Republican senators urge the Office of Management and Budget to release NIH funding. If this includes your state (AL, ME, WV, SC, KY, KS, AR, PA, NC, IN, AK), Sudip recommends contacting & thanking them for being American science leaders.

Bill Rutter passed away at age 97 yesterday. He chaired our Department through the 1970s and was instrumental in the development of UCSF basic science. He hired Christine Guthrie, Keith Yamamoto, Bruce Alberts, Marc Kirschner, Pat O’Farrell, Peter Walter, Ira Herskowitz among others.

In 2019, scientists discovered Jo Cameron, a Scottish woman with a rare genetic mutation that prevents her from feeling pain, anxiety, or fear and allows her to heal without scarring. | Science Acumen In 2019, scientists discovered Jo Cameron, a Scottish woman with a rare genetic mutation that prevents her from feeling pain, anxiety, or fear and allows her to heal without scarring. This condition...

Fascinating

www.linkedin.com/posts/scienc...

Child walks again after receiving experimental treatment for rare genetic condition NYU Langone researchers have helped an 8-year-old boy regain mobility using an experimental treatment.

Child walks again after receiving experimental treatment for rare genetic condition www.statnews.com/2025/07/09/n... via @statnews.com

Riboflavin drives nucleotide biosynthesis and iron-sulfur metabolism to promote acute myeloid leukemia https://www.biorxiv.org/content/10.1101/2025.06.26.661633v1

Dallas researchers find cancer’s secret weapon to defeat death Cancers use lipids to build a shield with vitamin E. Stripping that shield could lead to new treatments.

Today in @dallasnews.com by @sodendritic.bsky.social: "Dallas researchers find cancer’s secret weapon to defeat death" ⬇️ read more www.dallasnews.com/news/2025/06...
🧪 #relentlessdiscovery @rjdlab.bsky.social

Uridine Uridine is a pyrimidine nucleoside composed of an uracil base and a ribose sugar. In cells, uridine is predominantly present in RNA (as uridine monophosphate, UMP). Uridine can be produced through de ...

Uridine: Trends in Endocrinology & Metabolism www.cell.com/trends/endoc...

a great not-to-miss piece from the @lyssiotislab.bsky.social

Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes | NEJM Zimislecel is an allogeneic stem cell–derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed. We conducted a phase 1–2 study of zimisle...

What an amazing time to be a biomedical scientist.

www.nejm.org/doi/abs/10.1...

People With Severe Diabetes Are Cured in Small Trial of New Drug

Wow!!! 👏👏👏 Amazing to see this develop over the years!

www.nytimes.com/2025/06/20/h...

Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma Mitochondrial Ca2+ signaling regulates branched-chain amino acid catabolism in an adolescent liver cancer.

Our paper on regulation of BCAA catabolism by mitochondrial calcium signaling is out!
Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma | Science Advances www.science.org/doi/10.1126/...

Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay Zhang et al. identify a regulatory mechanism for how cells adapt to nutrient scarcity through widespread −1 ribosomal frameshifts, culminating in accelerated mRNA decay. This process, dependent on codon optimality and conserved across species, establishes direct feedback coupling the translation of new proteins with the stability of the mRNA that encodes for them.

Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay

Activation of lysosomal iron triggers ferroptosis in cancer - Nature Some cancer cells exhibit high loads of reactive iron in lysosomes, and this feature is exploited by using fentomycin-1, a newly developed small molecule, to induce ferroptosis.

new out in Nature, very cool story www.nature.com/articles/s41...

excited to share our latest work now online
@natmetabolism.nature.com, led by
@kyle-flickinger.bsky.social, where we unravel a mechanistic basis for the conditional essentiality of NADK, one of the many interesting hits from our previously reported CRISPR screening with HPLM rdcu.be/ekpu6

The Sable Award lecture at METPHYS2025 was really remarkable!

Tremendous congratulations to this years exceptional member of our community Kivanc Birsoy

And now, a note on Bill Owens who, until this past week, was the executive producer of 60 Minutes.

We’ll be back next week with another edition of 60 Minutes.

How cuts at the National Institutes of Health could impact Americans' health Cuts and layoffs to the National Institutes of Health threaten medical research around the U.S., agency insiders warn.

The National Institutes of Health, the largest funder of biomedical research in the world, has fired 1,300 employees and cancelled more than $2 billion in federal research grants. https://cbsn.ws/4daiCrv

From Nobel prize winning cancer researcher Bill Kaelin
Killing the Science Golden Goose - The American Journal of Medicine www.amjmed.com/article/S000...

Strength in numbers: tumor cells cooperate to survive under metabolic stress

Out on today's issue! :)

www.nature.com/articles/s41...

Here's the final program, for METPHYS2025

Really looking forward to the third edition of the Metabolic Physiology Meeting in 3 weeks !

If you haven't already registered, the link will stay open until April 15.

Hope to see you there!

www.sablesys.com/metphys2025-...

Opinion | Actually, A.I. Is Pretty Mid (Gift Article) A.I. is just what we need in the post-fact era: less research and more predicting what we want to hear.

Unsurprisingly, @tressiemcphd.bsky.social is spot-on in this analysis: “A.I.’s most revolutionary potential is helping experts apply their expertise better and faster. But for that to work, there has to be experts.”
www.nytimes.com/2025/03/29/o...

Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

SO excited to share that a major part of the postdoctoral work in @robzonculab.bsky.social lab is now published: “Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins” www.science.org/doi/10.1126/...

Cellular and organismal function of choline metabolism - Nature Metabolism

REVIEW | Kıvanç Birsoy, Monther Abu-Remaileh and colleagues @rockefelleruniv.bsky.social, @stanford.edu

The authors provide a broad overview of choline metabolism, its cellular handling, and how it impacts physiology and pathology.

https://bit.ly/3WPCPM2