DeBerardinis Lab at UT Southwestern Medical Center

Incredible chance to learn about genetics, from the fundamentals to the latest science. I attended this course when I was a PhD student in the 90s and have lectured in it for the last dozen or so.
And science aside, there's nowhere better to be in late July than Bar Harbor, ME. See you there.

#RareDiseaseDay2026: “think of zebras (rare diseases) when you hear hoofbeats.” On Feb 28, we wear stripes to recognize patients with rare diseases and support rare disease research in CRI and the McDermott Center at UT Southwestern. Thanks to the Rare Disease CoE for all you do for these patients.

12 panels total. No supplemental data. There are dot blots and a northern blot. It says "data not shown" at one point.
That was a different era.

Human enteric defensins. Gene structure and developmental expression - PubMed Paneth cells, secretory epithelial cells of the small intestinal crypts, are proposed to contribute to local host defense. Both mouse and human Paneth cells express a collection of antimicrobial proteins, including members of a family of antimicrobial peptides named defensins. In this study, data fr …

My first co-authored paper appeared 30 years ago today.
pubmed.ncbi.nlm.nih.gov/8626737/

Great time in Boston, as always! Thanks for the invitation!

CMTRA 2026 Annual Meeting | Cancer Molecular The Please use Join us for the CMTRA 2026 Annual Meeting at the spectacular Snowbird Mountain Resort in the Wasatch Mountains of Salt Lake City, Utah. Engage in insightful discussions, network with indust...

www.cancermoleculartherapeutics.org/event-detail...

That’s a wrap on the past 12 months, with even more #relentlessdiscovery to come in 2026. cri.utsw.edu/discoveries/

@seanjmorrison.bsky.social
@rjdlab.bsky.social
@haozhulab.bsky.social

🧪 #stemcells #regeneration #CancerResearch #metabolism #NYE2025 #NYE2026

Loss of vitamin C synthesis protects animals from schistosomiasis - Children's Medical Center Research Institute (CRI) | Dallas Texas Agathocleous Lab, collaborators discover vitamin C deficiency can benefit animals by depriving vitamin from parasitic worms DALLAS – Dec. 23, 2025 – Scientists at Children’s Medical Center Research In...

ONLINE NOW in @pnas.org: Agathocleous Lab, collaborators discover why humans, some animals may need intermittent vitamin C deficiency: to survive parasite infections. 🧪 Read more ⬇️ cri.utsw.edu/loss-of-vita... #relentlessdiscovery

My understanding is that he’s a specialist. Foggy only. Like a left handed reliever

This is why I write a little bit of magical thinking into all abstracts.

Just a nice lab happy hour before the holidays

Summer Undergraduate Research Experience (REU) | Cech Fellows | HHMI The Cech Fellows Program is a paid, nine-week summer research experience empowering the next generation of scientific leaders.

An excellent opportunity for summer undergraduate research - the Cech Fellows Program! Applications due in 10 days:
www.hhmi.org/programs/cec...

I have been saying this. It’s an abomination. The only thing that comes close is the Quizno’s spongmonkeys.

In Memoriam: Bert W. O'Malley, M.D. In Memoriam: Bert W. O'Malley, M.D....

A true legend.
www.bcm.edu/about-us/lea...

Regulated decay of microRNAs plays a critical role in controlling body size in mammals! Check out our new paper in @genesdev.bsky.social and see thread previously posted with our pre-print 👇 for more info. Congrats to Collette LaVigne, Jaeil Han, and all authors!
genesdev.cshlp.org/cgi/content/...

Here's the beautiful paper from @chembiohub.bsky.social reporting NUDT5's role in purine synthesis. I cannot emphasize enough how gracious and open these authors were when we all realized we were working on the same mechanism.

19/Work from the Yang group: www.jci.org/articles/vie...

Uridine-sensitized screening identifies genes and metabolic regulators of nucleotide synthesis Nucleotides are essential for nucleic acid synthesis, signaling, and metabolism, and can be synthesized de novo or through salvage. Rapidly proliferating cells require large amounts of nucleotides, ma...

18/Work from the Jourdain group: www.biorxiv.org/content/10.1...

A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...

17/NUDT5 is having a moment – see excellent work from other labs reporting roles for NUDT5 in purine metabolism. These include papers by Kilian Huber and Stefan Kubicek, also out today (see link), and work by Alexis Jourdain and Jun Yang (see next posts)
www.science.org/doi/10.1126/...

16/TL/DR: The DNPB pathway has been known since the 1950s, and thiopurines have been used almost as long. NUDT5 regulates the activity of this pathway, and sensitivity to drugs that block it.

15/A fascinating open question is exactly what induces the association between NUDT5 and PPAT, and whether/how this triggers disassembly of the purinosome.

14/When purines are abundant, the purinosome disassembles, but this requires NUDT5-PPAT binding. So NUDT5 controls both the biochemistry and cell biology of DNPB initiation.

13/Also interesting: DNPB involves a cytosolic complex called the purinosome, which colocalizes the DNPB enzymes together to channel metabolites along the pathway. NUDT5 regulates the purisonome through the same residues that bind PPAT.

12/Interestingly, NUDT5’s ability to suppress DNPB explains how it confers 6TG sensitivity. 6TG induces the same DNA damage in wild-type and NUDT5-deficient cells, but only the latter cells survive. Blocking residual DNPB kills NUDT5-deficient cells treated with 6TG.

11/The NUDT5-PPAT complex seems to hold PPAT into an inactive oligomer (likely a tetramer) that suppresses DNPB. In vitro, NUDT5 reduces PPAT enzymatic activity, much better than purine nucleotides alone. But this requires that NUDT5 associate with PPAT.

10/Mutating a single NUDT5 residue from the interface with PPAT eliminated NUDT5’s ability to bind PPAT and confer sensitivity to 6TG, both in cultured cells and xenografted tumors.

9/Zheng found that NUDT5’s catalytic activity is dispensable for its ability to confer sensitivity to 6TG. Rather, he found through interactome databases and computational analysis of coevolutionary signals that NUDT5 physically associates with PPAT.

8/NUDT5’s involvement was surprising. R5P provides the pentose for purines, but Zheng had shown that mitochondrial suppression massively increases R5P abundance by activating the pentose phosphate pathway. He thought NUDT5 might have a different role.

7/The screen identified HPRT1, the salvage enzyme that converts 6TG into toxic thiopurine nucleotides. That made sense. It also identified NUDT5, a hydrolase that cleaves ADP-ribose to produce ribose-5-phosphate (R5P).

6/Thiopurines are salvaged to produce thiopurine nucleotides, which inhibit DNPB and incorporate into DNA, resulting in DNA damage and cell death. So a screen for suppressors of 6TG toxicity could identify genes required to activate salvage or suppress DNPB.