Dr Ryan Duchatel

Had a wonderful afternoon playing monopoly supporting the #LittleLegsFoundation for beautiful Alegra. Thank you for all you do to support #dunlab and DIPG research. ⁦@evierjackson⁩ @mika persson

@evierjackson is an emerging research super star!

So great to see our review article on targeting CLPP out in print. Beautiful work from @evierjackson, @Mika_Persson97 and @MattDun17.

PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma: buff.ly/3TAz4Jd @MattDun17 @childrenshealth @Uni_Newcastle #Oncology #Therapeutics

@eddpasquier @julie__lafont @evierjackson @MattDun17 @Marion_Le_Grand @BaptisteMouyss1 @Kvin__M @crcm_marseille @translateitcrcm Thank you mate!

In today's Brioche Club, @julie__lafont presented the latest study from the #DunLab on targeting the PI3K/mTOR pathway in #DIPG. Beautiful work spearheaded by @duchatel_ryan and @evierjackson under the guidance of @MattDun17. We love these biology-guided drug combinations 🤩

Thank you @RobertReya for the fantastic and considered commentary on our recent @jclinicalinvest publication on PI3K/PKC in DIPG/DMG. jci.org/articles/view/…

Proud to see our paper targeting PI3K in DMG on the cover of JCI. Thank you to all those who assisted this work, in particular my amazing colleague @evierjackson and mentor @MattDun17.

#Cover: Targeting PI3K/mTOR in diffuse intrinsic pontine glioma: buff.ly/3TAz4Jd #Image presents a model whereby the connectivity of these cancers can be harnessed using integrated technologies to identify potential therapeutic strategies. #Oncology #Therapeutics

@DaniBeckman @MattDun17

Myelin and Covid I often post high-magnification photos, so sometimes it is hard (even for me in the microscope) to have an idea of the big picture of the damage that a microorganism like #SARSCoV2 can cause in the brain. The photos below are a comparison of the same region in the brain, with staining for degraded myelin only (dgMBP, 🟢), activated microglia (HLA-Dr, 🔴), and nuclei (dapi, 🔵). If the virus is able to infect neurons, like we think SARS-CoV-2 is, we often see a faster viral spread by using axonal transport. The virus basically hijacks the neuronal machinery for fast neural propagation and uses it to spread viral particles faster and to more brain regions. Viruses can destroy the axons; consequently, the myelin surrounding it shifts from healthy to degraded. It is suggested that such degenerative changes lead to cognitive decline because they cause changes in conduction velocity, disrupting neuronal circuits and contributing to neuronal loss. But besides that, we see that degraded myelin only attracts more activated microglia for the region, contributing to more neuroinflammatory responses in this region and others. But we also see that it is really hard to keep these events contained only to the olfactory cortex. I strongly believe all these neuroinflammatory responses contribute to "brain fog" and #LongCovid. These processes can start very fast but can be very slow for the brain's immune system to clean up the mess after it. #neuroscience #CovidIsntOver

Thank you @CureStartsNow @CureStartsNowAU for the Valentine’s Day treats!

@FaValdesMora, @maria_tsoli, @ProfDavidZieg, @MurrayCairns, @VitanzaNick, @timphoenixUC, @CarlKoschmann, @neuronewy, @auscancadoc, @NazarianLabs, @JaseCain. @evierjackson (11/11)

This project was truly collaborative, with a number of researchers and groups contributing from across many countries. @DKiltschewskij, @DilanaStaudt, @Bryce_Thomas23, @Zacger, @DrLizzieManning, @DeVerrills, @DavidSkerrettB, @BrettNixon13, @DrSusanHua, @charles_debock (10/11)

The combination of paxalisib and the PKC inhibitor Enzastaurin synergistically extended the survival of a number of aggressive pre-clinical DIPG/DMG models. (5/11)

To identify rational combination strategies to enhance PI3K inhibition we integrated RNA-seq and quantitative phosphoproteomic profiling, and identified the activation of Protein Kinase C (PKC) in DIPG/DMG cells when treated with Paxalisib. (4/11)

Proud to highlight the recent publication of our #DunLab project (@MattDun17) in @jclinicalinvest identifying PI3K as a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma (DIPG/DMG). Thread... (1/11) jci.org/articles/view/…

Clinically, resistance to PI3K inhibitors is mediated by insulin feedback caused by hyperglycemic side effects following PI3K inhibition. Paxalisib in combination with the anti-glycemic drug metformin reduced these side effects and improved efficacy in pre-clinical models. (3/11)

CRISPR-Cas9 screening identified PIK3CA and MTOR as genetic dependencies in all 38 DIPG/DMG models studied and sensitivity to the blood brain barrier penetrant, PI3K inhibitor paxalisib, independent of mutational states @KaziaTx (2/11)