Aird lab trainees Raquel, Kelly, and Erika present their work at the International Cellular Senescence Association meeting

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The International Cellular Senescence Association meeting is underway in Athens. Raquel was chosen for a short talk, and both Kelly and Erika presented posters of their work.

Raquel giving a talk on her recently published work on how p16 loss increases nucleotide metabolism to bypass senescence.

Raquel giving a talk on her recently published work on how p16 loss increases nucleotide metabolism to bypass senescence.

Kelly presenting her work on how the methyltransferase DOT1L is critical for the SASP

Kelly presenting her work on how the methyltransferase DOT1L is critical for the SASP

Erika presenting her work on senescence in the omentum and how that potentially relates to ovarian cancer dissemination

Erika presenting her work on senescence in the omentum and how that potentially relates to ovarian cancer dissemination

Raquel's paper is published in Cell Reports!

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Congratulations to Raquel and the lab for publishing this exciting story! She found that loss of p16 increases nucleotide metabolism via mTORC1-mediated translation of the pentose phosphate pathway enzyme RPIA. Excitingly, inhibition of this pathway may be a new therapeutic strategy for the ~50% of cancer patients with low p16 expression.

You can read the paper here.

Aird Lab receives research grant from the Sandy Rollman Ovarian Cancer Foundation!

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We are excited and honored to be supported by the Sandy Rollman Ovarian Cancer Foundation! This work will investigate the role of metabolism in PARP inhibitor response and is a direct follow-up to Erika’s excellent work on wildtype IDH1 in ovarian cancer. For more information on the foundation, please visit their website: https://sandyovarian.org

Congratulations to Erika for submitting her manuscript on IDH1 in ovarian cancer

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Erika submitted her 1st first author paper! Read the preprint here.

She found IDH1 by looking at metabolites in fallopian tube cells compared to high grade serous ovarian cancer cells. Interestingly, while glycolytic metabolites were not consistently altered, TCA cycle metabolites were universally high in the cancer cells. This suggests that targeting the TCA cycle is a therapeutic strategy for high grade serous ovarian cancer. When she looked at TCA cycle enzyme expression, IDH1 stood out because it was high and associated with worse progression-free survival. Pharmacological inhibition or genetic knockdown of wildtype IDH1 inhibited proliferation by inducing senescence, a stable cell cycle arrest. She discovered that this was through an increase in repressive H3K9me2 and proliferation-promoting gene loci. Her data indicate that wildtype IDH1 can be targeted in high grade serous ovarian cancer. There are inhibitors in clinical trials that inhibit the wildtype enzyme- we will further work to see whether we can use these for ovarian cancer patients. This is another example of the interplay between metabolism and epigenetics.