Brett Chrest
@chrestbrett.bsky.social
PhD student with expertise in Mitochondrial Bioenergetics & Cancer Metabolism┃KFW Lab┃Investigating SUCL Enzymes, Respiratory & Energy Limitations in AML🩸
Reposted by Brett Chrest
1/New paper from Zheng Wu, Phong Nguyen et al. @cri-utsw.bsky.social shows how cells balance the two pathways that produce purine nucleotides: de novo purine biosynthesis (DNPB) and purine salvage. The surprising mechanism involves NUDT5, a Nudix hydrolase
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT
Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...
www.science.org
November 6, 2025 at 7:01 PM
1/New paper from Zheng Wu, Phong Nguyen et al. @cri-utsw.bsky.social shows how cells balance the two pathways that produce purine nucleotides: de novo purine biosynthesis (DNPB) and purine salvage. The surprising mechanism involves NUDT5, a Nudix hydrolase
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by Brett Chrest
An Amazing Cancer Biology Department Driving Advances Across Advocate Health - Ruben Mesa
@rubenmesamd.bsky.social
oncodaily.com/blog/ruben-m...
#OncoDaily #Oncology #Cancer #Health #Medicine #MedEd #MedOnc #MedNews
@rubenmesamd.bsky.social
oncodaily.com/blog/ruben-m...
#OncoDaily #Oncology #Cancer #Health #Medicine #MedEd #MedOnc #MedNews
Ruben Mesa: An Amazing Cancer Biology Department Driving Advances Across Advocate Health - OncoDaily
Ruben Mesa: An Amazing Cancer Biology Department Driving Advances Across Advocate Health / advocate health, Atrium Health, cancer, cancer biology, OncoDaily,
oncodaily.com
September 14, 2025 at 1:30 PM
An Amazing Cancer Biology Department Driving Advances Across Advocate Health - Ruben Mesa
@rubenmesamd.bsky.social
oncodaily.com/blog/ruben-m...
#OncoDaily #Oncology #Cancer #Health #Medicine #MedEd #MedOnc #MedNews
@rubenmesamd.bsky.social
oncodaily.com/blog/ruben-m...
#OncoDaily #Oncology #Cancer #Health #Medicine #MedEd #MedOnc #MedNews
Some caution around isolated enzyme experiments, I love this example:
SUCL activity is due to succinyl-CoA production from AKGDH. Thus you can genetically down regulate AKGDH, isolate mitochondria and test maximal SUCL activity and see no difference.
pmc.ncbi.nlm.nih.gov/articles/PMC...
SUCL activity is due to succinyl-CoA production from AKGDH. Thus you can genetically down regulate AKGDH, isolate mitochondria and test maximal SUCL activity and see no difference.
pmc.ncbi.nlm.nih.gov/articles/PMC...
The negative impact of α-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation
A decline in α-ketoglutarate dehydrogenase complex (KGDHC) activity has been associated with neurodegeneration. Provision of succinyl-CoA by KGDHC is essential for generation of matrix ATP (or GTP) by...
pmc.ncbi.nlm.nih.gov
September 13, 2025 at 4:49 AM
Some caution around isolated enzyme experiments, I love this example:
SUCL activity is due to succinyl-CoA production from AKGDH. Thus you can genetically down regulate AKGDH, isolate mitochondria and test maximal SUCL activity and see no difference.
pmc.ncbi.nlm.nih.gov/articles/PMC...
SUCL activity is due to succinyl-CoA production from AKGDH. Thus you can genetically down regulate AKGDH, isolate mitochondria and test maximal SUCL activity and see no difference.
pmc.ncbi.nlm.nih.gov/articles/PMC...
Reposted by Brett Chrest
Quite an essay on the basis of cancer entitled "The End of the Genetic Paradigm of Cancer" @plosbiology.org arguing against the primacy of somatic mutations (traditional model) and cells, invoking gene regulatory networks and tissue
journals.plos.org/plosbiology/...
journals.plos.org/plosbiology/...
March 18, 2025 at 6:25 PM
Quite an essay on the basis of cancer entitled "The End of the Genetic Paradigm of Cancer" @plosbiology.org arguing against the primacy of somatic mutations (traditional model) and cells, invoking gene regulatory networks and tissue
journals.plos.org/plosbiology/...
journals.plos.org/plosbiology/...
Reposted by Brett Chrest
1/For over a decade, we’ve been studying tumor metabolism in patients with non-small cell lung cancer
This long-term commitment allowed us to connect tumor metabolic features to patient outcomes
We found that 13C glucose contribution to the TCA cycle predicts overall survival in NSCLC
This long-term commitment allowed us to connect tumor metabolic features to patient outcomes
We found that 13C glucose contribution to the TCA cycle predicts overall survival in NSCLC
Now online in Cancer Discovery: High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients - by Ling Cai, Nia Hammond, Brandon Faubert, @rjdlab.bsky.social, and colleagues doi.org/10.1158/2159...
February 17, 2025 at 8:20 PM
1/For over a decade, we’ve been studying tumor metabolism in patients with non-small cell lung cancer
This long-term commitment allowed us to connect tumor metabolic features to patient outcomes
We found that 13C glucose contribution to the TCA cycle predicts overall survival in NSCLC
This long-term commitment allowed us to connect tumor metabolic features to patient outcomes
We found that 13C glucose contribution to the TCA cycle predicts overall survival in NSCLC
Reposted by Brett Chrest
A great talk from Navdeep Chandel today at the Molecular and Cellular Oncology (MCO) retreat for the Comprehensive Cancer Center today. All things #mitochondria in #cancer and other diseases. Great talks from all the other faculty as well.
@rubenmesamd.bsky.social
🐪🏙️🦀🧬
@rubenmesamd.bsky.social
🐪🏙️🦀🧬
December 13, 2024 at 8:08 PM
A great talk from Navdeep Chandel today at the Molecular and Cellular Oncology (MCO) retreat for the Comprehensive Cancer Center today. All things #mitochondria in #cancer and other diseases. Great talks from all the other faculty as well.
@rubenmesamd.bsky.social
🐪🏙️🦀🧬
@rubenmesamd.bsky.social
🐪🏙️🦀🧬
While fundamental, gene expression & signalling pathways are often oversimplified, especially, in the oncological context. Outputs are probabilistic, not deterministic. Not an off/on switch, but broadening and heterogeneity of the amplified signal.
www.youtube.com/watch?v=WiJo...
www.youtube.com/watch?v=WiJo...
December 5, 2024 at 11:23 PM
While fundamental, gene expression & signalling pathways are often oversimplified, especially, in the oncological context. Outputs are probabilistic, not deterministic. Not an off/on switch, but broadening and heterogeneity of the amplified signal.
www.youtube.com/watch?v=WiJo...
www.youtube.com/watch?v=WiJo...
DNMT3A mutations were dispensable for AML maintenance. Replacing mutants with wild-type did not impair engraftment. DNMT3A mutations are necessary for AML initiation, but dispensable for disease maintenance. Initiating oncogenes differ from maintenance.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
DNMT3AR882H Is Not Required for Disease Maintenance in Primary Human AML, but Is Associated With Increased Leukemia Stem Cell Frequency
Genetic mutations are being thoroughly mapped in human cancers, yet a fundamental question in cancer biology is whether such mutations are functionally required for cancer initiation, maintenance of e...
www.biorxiv.org
November 24, 2024 at 5:13 PM
DNMT3A mutations were dispensable for AML maintenance. Replacing mutants with wild-type did not impair engraftment. DNMT3A mutations are necessary for AML initiation, but dispensable for disease maintenance. Initiating oncogenes differ from maintenance.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Brett Chrest
Clear and comprehensive new go-to review from #NoTwitterNav (we're gonna need a new hashtag) delineating how mitochondria have distinct and context-specific roles in proliferation and fate determination www.annualreviews.org/content/jour...
www.annualreviews.org
November 14, 2024 at 7:30 PM
Clear and comprehensive new go-to review from #NoTwitterNav (we're gonna need a new hashtag) delineating how mitochondria have distinct and context-specific roles in proliferation and fate determination www.annualreviews.org/content/jour...
Diving into mSLP for part of my PhD.
Discussed here, and in other papers (even back to 2004), SUCLA2 and SUCLG2 are not interchangeable and can lack compensatory activity for one another. This fact is lost in many textbooks & graphical depictions of the TCA cycle.
Discussed here, and in other papers (even back to 2004), SUCLA2 and SUCLG2 are not interchangeable and can lack compensatory activity for one another. This fact is lost in many textbooks & graphical depictions of the TCA cycle.
Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion - Oncogene
Oncogene - Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion
www.nature.com
November 15, 2024 at 10:51 PM
Diving into mSLP for part of my PhD.
Discussed here, and in other papers (even back to 2004), SUCLA2 and SUCLG2 are not interchangeable and can lack compensatory activity for one another. This fact is lost in many textbooks & graphical depictions of the TCA cycle.
Discussed here, and in other papers (even back to 2004), SUCLA2 and SUCLG2 are not interchangeable and can lack compensatory activity for one another. This fact is lost in many textbooks & graphical depictions of the TCA cycle.
Looks like it is time for an attempt to rebuild on this platform! 🙏
November 10, 2024 at 5:19 PM
Looks like it is time for an attempt to rebuild on this platform! 🙏