Publications by authors named "Katelyn J Noronha"
Poly (ADP-ribose) glycohydrolase (PARG) inhibitors are currently under clinical development for the treatment of DNA repair-deficient cancers; however, their precise mechanism of action is still unclear. Here, we report that PARG inhibition leads to excessive PARylated poly (ADP-ribose) polymerase 1 (PARP1) reducing the ability of PARP1 to properly localize to sites of DNA damage. Strikingly, the mis-localized PARP1 accumulates as aggregates throughout the nucleus.
View Article and Find Full Text PDFHereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten-eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation.
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- The treatment of primary central nervous system tumors like glioblastomas (GBM) is hindered by the blood-brain barrier and complicated mutations, resulting in low survival rates; recent findings show that common mutations in gliomas affect NAD+ production through the NAPRT gene.* -
- NAPRT silencing creates a weakness in these tumors, enabling the use of inhibitors targeting another enzyme in the NAD+ pathway (NAMPT), but existing NAMPT inhibitors face significant side effects limiting their effectiveness.* -
- A novel method using nanoparticle-encapsulated NAMPT inhibitors delivered directly into the brain has shown promising results, reducing side effects while significantly delaying tumor growth and improving survival in mouse models of GBM.*
Retinal dopamine is a critical modulator of high acuity, light-adapted vision and photoreceptor coupling in the retina. Dopaminergic amacrine cells (DACs) serve as the sole source of retinal dopamine, and dopamine release in the retina follows a circadian rhythm and is modulated by light exposure. However, the retinal circuits through which light influences the development and function of DACs are still unknown.
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