Alexandra Perlegos

Postdoc at Genentech in the Henri Jasper Lab | Neuroscience PhD | Previously @PennNGG studying m6A in aging Drosophila brain with Nancy Bonini. Views my own.

[Alexandra Perlegos @AlexPerlegos]

Absolutely thrilled to share our latest work in @Aging_Cell! We delve into #m6A modification in the #Drosophila brain with #aging and #neurodegenerative disease, with opposing impacts in #neurons vs #glia. Detailed summary of our findings in this thread! 🧵https://t.co/JtXSJCFpAX

[Alexandra Perlegos @AlexPerlegos]

Excited to see our hard work in print! 🪰🧠 Congratulations @chinabyrns and everyone on the team!
#BoniniLab #Drosophila #Senescence #BrainAging

https://t.co/IQQ9KKM3rQ

[nature @Nature]

Nature research paper: Senescent glia link mitochondrial dysfunction and lipid accumulation https://t.co/toUhZCtxfC

[ShorterLab @ShorterLab]

Mo’ m1A, mo’ problems: https://t.co/Fx5sclAxcJ

[Alexandra Perlegos @AlexPerlegos]

8/ Overall this work indicates m6A has critical implications for brain integrity with age and disease. Neurons and glia show distinct responses to m6A loss, elucidating its potential contribution to age-related neurodegeneration and the hindered stress response of the brain.

[Alexandra Perlegos @AlexPerlegos]

7/ Through TRAP profiling we found that Mettl3 loss increases translational efficiency of m6A transcripts in neurons but decreases translation in glia. This nuanced regulation highlights the diverse impact of m6A modification in different cell types within the brain.

[Alexandra Perlegos @AlexPerlegos]

6/ Exploring glial tauopathy models, we found Mettl3 knockdown in glia reduced pathological tau puncta and extended lifespan in this model.

[Alexandra Perlegos @AlexPerlegos]

5/ Surprisingly, Mettl3 knockdown in glial cells extended lifespan and reduced DNA damage levels with age. Underscoring two opposite avenues of m6A regulation in the brain with age, dependent on the cell-specific expression levels of the transcripts being regulated.

[Alexandra Perlegos @AlexPerlegos]

Absolutely thrilled to share our latest work in @Aging_Cell! We delve into #m6A modification in the #Drosophila brain with #aging and #neurodegenerative disease, with opposing impacts in #neurons vs #glia. Detailed summary of our findings in this thread! 🧵https://t.co/JtXSJCFpAX

[Alexandra Perlegos @AlexPerlegos]

4/ Knockdown of m6A methyltransferase, Mettl3, in neurons decreased overall lifespan, affecting nervous system integrity. DNA damage levels are increased in aged brains, and loss of Mettl3 exacerbated DNA damage levels.

[Alexandra Perlegos @AlexPerlegos]

3/ In a Drosophila Alzheimer's model, we observed a similar response, with increased m6A levels and decreased transcript levels in Aβ42 brains. There was some overlap in RNAs affected (signaling and neurogenesis pathways) with distinct pathways in disease (stress-response)

[Alexandra Perlegos @AlexPerlegos]

2/ In the aged Drosophila brain m6A levels increased in the 5'UTR of transcripts enriched for critical signaling and neurogenesis pathways. These transcripts tend to be down with age. Revealing a set of transcripts that increase m6A levels and decrease transcripts levels with age

[Alexandra Perlegos @AlexPerlegos]

9/ Looking forward to seeing the many directions this work will go as we explore additional modifiers of the TDP-43 sleep phenotype! Absolutely loved working with the @kayserlab and #Boninilab and they are looking for new postdocs and grad students to carry on the work! 🔥

[Alexandra Perlegos @AlexPerlegos]

Excited to share our findings linking TDP-43, sleep disruption, and metabolic disruption! Congratulations to the whole team! @KayserLab, @SamyBelfer, JackieDurkin, @kristenhpark, @Anyara_Rod 🧠💤 https://t.co/j9vC7s8eGc @ScienceAdvances #ALS #FTD #sleep #Drosophila

[Alexandra Perlegos @AlexPerlegos]

8/ 💡 Overall, our study unveils intricate connections between TDP-43 toxicity, sleep disruptions, and metabolic pathways. These findings open new avenues for understanding and potentially treating sleep disturbances associated with neurodegenerative diseases.