Katherine’s American Cancer Society Research Scholar Grant was recently funded! The grant will help us better understand metabolic dysregulation early in ovarian tumorigenesis and determine whether metabolic inhibitors can be used in combination with PARP inhibitors to improve ovarian cancer therapy.
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.
Erika Dahl, 4th year graduate student, received the Patrick G. Quinn award for outstanding post-candidacy doctoral student in C&M Physiology department on Friday at the Antique Auto Museum. Congrats Erika!
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.
Raquel’s paper describing a new, cell cycle-independent role for p16 loss in promoting pro-tumorigenic nucleotide metabolism has been accepted by Cell Reports. You can read the preprint on bioRxiv here.
Congratulations to Raquel!
Graduate student Kelly Leon presented her work on the epigenetic control of the senscence-associated secretory phenotype. It was a great day of clinical and basic science! Postdoc Daniel Chen presented his work on glucose regulation in ATM inhibitor-treated cells. It was a great day of clinical and basic science!
We are delighted to announce that Erika’s IDH1 metabolism and epigenetics paper has been accepted! Not only is this Erika’s first first author paper, but it is also the first research paper from the lab! Huge congratulations to Erika! We will post the link once the paper is posted.
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
Erika is now funded by an F31 from the NCI to study metabolism in cyclin E-high ovarian cancer! What a huge accomplishment!
Congratulations to Kelly Leon, 2nd year grad student, whose review on JmjC demethylases in senescence was just accepted! Update Jan 9: here is a link to the review: https://www.mdpi.com/2073-4425/10/1/33
Congratulations to Erika for winning best poster award for her work Targeting IDH1 as a Pro-senescent Therapy for High Grade Serous Ovarian Cancer!
Raquel was awarded a 2-year internal fellowship to study the role of p16-loss-mediated anti-tumor immunity!
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.
The lab’s work and team spirit were featured on the Penn State Medicine website! Check out the article: https://pennstatemedicine.org/2018/09/25/team-research-reveals-how-cells-eat-and-sleep-may-impact-several-cancer-types/