Milan Savani
milansavani.com
Medical student at UT Southwestern. PhD from the McBrayer Lab at the Children's Research Institute @ UTSW. | nitrogen metabolism in glioma | he/him
👤 Joined on 19 November 2023
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- 19 Kas 2023, 06:27
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11/ In addition to first authors Kalil Abdullah, Kenji Miki, Charley Edgar, Shuangcheng Wu & @yixiao.bsky.social, other collaborators included @rjdlab.bsky.social, @michellemonje.bsky.social, Kim Huber, Jay Gibson, @herveyjumper.bsky.social, Simon Chamberland, @mathews-tom.bsky.social & many others.
Show Post10/ This work connects cancer metabolism & cancer neuroscience. Drawing on a rare metabolic disease, it shows how gliomas rewire creatine metabolism to produce GAA and increase neuronal activity, which drives tumor growth. These findings identify GAA as a potential targetable vulnerability of HGGs.
Show Post9/ The link to GAMT deficiency suggested another way to test the model. Dietary arginine restriction plus ornithine supplementation lowers GAA and reduces seizures in patients with GAMT deficiency. Applying this diet to glioma-bearing mice reduced tumoral GAA levels and attenuated glioma growth.
Show Post8/ Is GAA-driven neuronal hyperexcitability required for tumor growth? AGAT knockout depleted GAA without impairing glioma growth in monoculture. Yet, in mouse brain, it reduced neuronal activity and prolonged survival, indicating that GAA’s oncogenic effects depend on the neural microenvironment.
Show Post7/ The answer lies in neuronal chloride homeostasis. Neurons near HGG cells have elevated intracellular Cl-, partly due to reduced KCC2 expression, making GABAA receptor signaling depolarizing. Indeed, GAA increased neuronal firing in HGG-infiltrated brain, but not in the contralateral hemisphere.
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