EPAS1/HIF2α A530V (gain-of-function variant, oxygen-insensitive)
#VascularMalformation

👉Human N=9 (16-63 y/o)
Retinal capillary hemangioma
Ocular/Spinal venous malformation
Intracranial venous/cavernous malformation

+Evidence of Epas1 A529V🐭

@insight.jci.org 2021
insight.jci.org/articles/vie...

Congrats to the newest PhD from the @siegenthalerlab.bsky.social, Dr. Sophia Kim! Beautiful thesis document & presentation! 🧠🦠🔬🎉

Sophia's thesis work on arachnoid barrier breakdown in meningitis is on bioRxiv - check it out!
www.biorxiv.org/content/10.6...

Newly identified barrier cells seal off choroid plexus from CSF, rest of brain A long-overlooked layer of fibroblasts exists inside the choroid plexus of mice and humans, adding complexity to the area’s compartmentalization.

Fibroblasts play an important role in the compartmentalization of the choroid plexus, according to new work in mice.

By @claudia-lopez.bsky.social

#neuroskyence

www.thetransmitter.org/choroid-plex...

Some of my PhD work is now published in @mucosalimmunol.bsky.social!

Osteoclast-mediated skull bone channel remodeling influences meningeal immune infiltration upon challenge
www.science.org/doi/10.1126/... @sciimmunology.bsky.social
spotlight of @cp-immunity.bsky.social
linkinghub.elsevier.com/retrieve/pii...

Microglia-glioblastoma crosstalk mediates glioblastoma invasion at the far infiltration zone @cp-immunity.bsky.social
www.cell.com/immunity/ful...

Age-related NF-κB activation in fibroblasts remodels the lung resident immune system and promotes the emergence of pro-inflammatory Gzmk+ T cells @cp-immunity.bsky.social
www.cell.com/immunity/ful...

Distinct origins and niches determine the cellular responsiveness of CNS macrophages after repopulation - Nature Immunology Prinz and colleagues examine the distinct functions and repopulation properties of leptomeningeal and perivascular macrophages that mediate immune responses at brain boundaries.

New insights on brain macrophage repopulation by the Prinz group:

Distinct origins and niches determine the cellular responsiveness of CNS macrophages after repopulation | @natimmunol.nature.com

www.nature.com/articles/s41...

Next Generation Leaders The Next Generation Leaders program at the Allen Institute aims to support emerging and diverse early-career researchers in bioscience who will contribute to cultivating new ideas to make a broad, tra...

Immunology at the Allen Institute is looking for next generation leaders, particularly those working in neuroimmunology and creating AI models in human disease. Please apply if you are interested in collaborating with other scientists at the Allen Institute alleninstitute.org/about/people...

Sex-specific APOE4-dependent innate immunity regulates meningeal lymphatics, brain lipids, neuroinflammation, and cognition Delivanoglou et al. show that expression of APOE4, a risk factor for Alzheimer’s disease, leads to sexually dimorphic lymphatic and inflammatory responses in mice and humans alike. Suppressing APOE4-i...

Sex-specific APOE4-dependent innate immunity regulates meningeal lymphatics, brain lipids, neuroinflammation, and cognition: Neuron www.cell.com/neuron/fullt...

🚨 Our study is online @cp-neuron.bsky.social!
A fun read for all you neuroimmunology aficionados!
This study proposes that targeting innate immunity/lymphatics in female & male E4 carriers might lead to different cognitive outcomes, highlighting the need for immunotherapies tailored to each sex. 👇

@tcpotts.bsky.social paper is live. Happy to share #FishNAP, a new, non-invasive way to measure #BBB permeability in 96-well format with #zebrafish www.biorxiv.org/content/10.6...

Congrats Julie!!

🚨 Our search for a postdoctoral researcher is still on!
Contact me if you feel passionate about investigating neuroimmune mechanisms in neurodegenerative disorders.
Candidates should have proven experience with rodent models of neurodegenerative disorders.

Brain-engrafted monocyte-derived macrophages from blood and skull-bone marrow exhibit distinct properties. @cp-neuron.bsky.social www.cell.com/neuron/fullt...

Integrative CSF profiling identifies disease-specific immune responses in leptomeningeal disease
@cp-cellrepmed.bsky.social
www.cell.com/cell-reports...

Its definitely a cool story and has come a long way since the CSHL meeting. Decided against GRC in the end, would have loved to go, but with new students and postdocs starting wanted to make sure I was on hand for them. Major FOMO but hopefully will be back in a couple of years with an entourage 😁

Congrats Julie and Sophia! Looks great and the TNF data are particularly interesting! 🤩

graphical schematic of the meninges on top depicting the three layers [dura, arachnoid and pia] and other immune and vascular cell types. Inset shows Claudin-11 junction proteins connecting two sides of arachnoid barrier cells bottom schematic is the same but in inflammation with bacteria, junctions breakdown, depiction of cytokine release by vascular, meningeal and immune cells - at side of graphic is summary of defects we observe in infection: 'increased barrier permeability' 'mislocalization of Cldn11+ tight junction' 'BAM activation' and "increased inflammatory response'

🚨 New preprint from our lab led by Sophia Kim w/ @kellydoran.bsky.social group @cuanschutz.bsky.social -- using neonatal 🐭 model of bacterial meningitis ➡️ arachnoid barrier is leaky, Cldn11 junctions are disrupted & cytokines are part of the problem. Lots of 🤩🧠🦠🔬 & compelling data, check it out! 1/5

Amyloidosis of bridging veins is a pathologic feature of #Alzheimers disease, from @leonsmyth.bsky.social, Rupal Mehta, @jonykipnis.bsky.social et al. rupress.org/jem/article/...

📘 In our #Lymphatics collection: rupress.org/jem/collecti...

Autoimmune neuroinflammation leads to neuronal death via MIF nuclease-mediated parthanatos Nature Neuroscience - Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective...

How does inflammation kill neurons, and what can we do about it? Check out our latest paper where we consider this question: rdcu.be/e4nfP.

The Da Mesquita lab at Mayo Clinic (www.mayo.edu/research/lab...) is looking for a postdoctoral researcher to work on projects investigating the role(s) of the meningeal lymphatic vasculature in models of neurodegenerative diseases. Please spread the word and contact me in case you are interested! 😃

Base barrier cells provide compartmentalization of choroid plexus, brain and CSF - Nature Neuroscience Verhaege et al. identify a conserved fibroblast barrier population at the base of the choroid plexus that compartmentalizes brain–CSF interfaces and is disrupted by inflammation, revealing a new site ...

Base barrier cells provide compartmentalization of choroid plexus, brain and CSF | Nature Neuroscience

www.nature.com/articles/s41...

Review @natrevdrugdiscov.nature.com
Therapeutic targeting of neuroimmune mechanisms in neurodegeneration
www.nature.com/articles/s41...

First proof-of-concept for engineered T cells as a potential treatment for Alzheimer's disease
pnas.org/doi/10.1073/...

Yeah the morphology surely governing a lot of this, and perhaps the more limited set of junctional proteins that they express. Would be super cool to know more about the function!

Very interesting, the junction structure looks different too - lots of buttons… 🤔

ZO1 in the pia? 😮

Scientific Editor, Cell Cell has an opening for a full-time scientific editor. If you are a passionate, mission-driven team player who loves thinking broadly about science and wants to have a positive impact, we invite you t...

Cell is hiring!

Do you have a background in #neuroscience or #immunology? Better still, #neuroimmunology? Cell has an opening for a full-time scientific editor. Role will be based out of any one of our offices in Medford, MA, UK, Spain, Netherlands, China tinyurl.com/4ma236xn @cp-cell.bsky.social