@JM_Castell

Associate Professor & PI @SinaiBrain / @IcahnMountSinai, Neuroscientist studying blood-brain communication in aging and Alzheimer's / views expressed are my own

 New York, NY
castellanolab.org
Joined March 2017
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7Media
Happy to share the lab's new work characterizing the impact of a youth-associated protein on microglial function. Congrats to 1st author Brittany Hemmer, w/ excellent contributions f/ @philippi_sarah and all co-authors! @IcahnMountSinai @SinaiBrain Paper: nature.com/articles/s41467-0…

Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice

Nature Communications - Aging disrupts microglial function, but factors that rejuvenate these cells are poorly characterized. Here, the authors show the youth-associated protein TIMP2 revitalizes...

nature.com
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Joseph Castellano retweeted
Friedman Brain Institute@SinaiBrainAug 12
NEW STUDY! Researchers Brittany Hemmer, @JM_Castell, et al. ID TIMP2 as potential molecular link btwn youthful systemic factors & healthier brain immune function, providing new insight into how age-related changes in brain may be modified. @NatureComms 👉 nature.com/articles/s41467-0…
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Friedman Brain Institute@SinaiBrainJul 24
NEXT WEEK! On Tues, July 28, 10am, the #BrainBodySeminarSeries is excited to welcome @GladstoneInst's @andcyang. Join hosts @cam_phd & @JM_Castell when Dr. Yang presents "Tracing proteomes & immune cells across the #BloodBrainBarrier". Register Now 👉 mountsinai.zoom.us/webinar/r…
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CCAD
@The_CCADMar 21
Our next Zoom Your Career webinar is coming up! Join us 4/13 at 1PM EST for a conversation on mentorship and building healthy lab culture. Scan the QR code to register or the link ➡️ us02web.zoom.us/meeting/regi…
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Joseph Castellano retweeted
CCAD
@The_CCADMar 16
Join us on 4/13 at 1 PM ET for our next Zoom Your Career webinar! You will hear from Srikant Rangaraju, along side Derek Archer and Andrea Weinstein, with Joseph Castellano moderating the conversation. Register ➡️ us02web.zoom.us/meeting/regi…
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Friedman Brain Institute@SinaiBrainFeb 26
NOT TO MISS | A special #BrainAwarenessWeek event! On Friday, March 27, 10am, JOIN Dr. @JM_Castell when he hosts @Stanford's Dr. @wysscoray at this special #BrainBodyResearchInstitute Seminar Series Lecture. In-Person and via Zoom. Register Now 👉 mountsinai.zoom.us/webinar/r…
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Erik Musiek@ErikMusiek23 Oct 2025
Our glial circadian atlas in AD and aging mice is now out in @NatureNeuro! Congrats to @patwsheehan for incredible work and to our collaborators @johnthefryer, @CarpeRibosomam, @darshan1s, Ron Anafi, and the team. @johnthefryer and I started this in 2019! nature.com/articles/s41593-0…

A glial circadian gene expression atlas reveals cell-type and disease-specific reprogramming in...

Nature Neuroscience - Sheehan et al. have characterized the circadian translatomes of astrocytes and microglia in the mouse cortex in the context of amyloid pathology or aging, revealing cell- and...

nature.com
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Erik Musiek@ErikMusiek1 Sep 2025
I'm excited that @Jjiyeon_lee's 2nd paper from the lab is out in @NatureAging. We found that the circadian gene REV-ERBalpha regulates brain NAD+ by controlling CD38 in astrocytes. REV-ERB KO or pharmacologic inhibition mitigates tau pathology in mice. nature.com/articles/s43587-0… – at United States
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Excited to share a new preprint out from the lab (biorxiv.org/content/10.1101/…) by 1st-author @brittany_hemmer , a newly minted PhD from the lab! A brief thread on what we found (1/n):

Youth-associated protein TIMP2 alters microglial state and function in the context of aging

There is little understanding of how aging serves as the strongest risk factor for several neurogenerative diseases. Specific neural cell types, such as microglia, undergo age-related maladaptive...

biorxiv.org
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TIMP2 ⬇️ microglial activation, ⬆️ phagocytosis, and ⬇️ the proportion of microglia associated with deleterious processes, including pro-inflammatory processes and senescence—essentially reversal of several age-associated microglial phenotypes. (5/n)
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Overall, our work supports that TIMP2 (and likely other unexplored youth-associated factors) could be important for reducing microglial dysfunction in age-related disorders. Thanks for reading! (end).
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TIMP2 deficiency ⬆️microgliosis, ⬇️phagocytosis, and induces transcriptomic changes associated w/ activation + cytokine production. Hippocampal microdialysis revealed that TIMP2 loss ⬆️cellular stress and inflamm. proteins in the extracellular space. (3/n)
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Since key changes in microglia are seen regardless of which TIMP2 pool is targeted, we wondered if ⬆️the extracellular pool mitigates age-related microglial changes. Since TIMP2 gets into brain f/ blood, we gave aged mice systemic TIMP2 injections. (4/n)
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🎉Thrilled to announce that my awesome PhD student, @brittany_hemmer , successfully defended her thesis! Her thesis work is now preprinted (brief summary to follow)—proud of her hard work and perseverance!
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Special thanks to her fantastic committee, incl. her committee chair @lab_schaefer (pictured), @ScottRussoPhD , @cam_phd , and @LucasCheadle for invaluable guidance. She's seeking postdoc opps. in the Boston area (incl. NH/RI)—reach out if interested! #PhDone #ProudAdvisor
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CCAD
@The_CCAD17 Apr 2025
Join us on Monday, April 21st for our next #ZoomYourCareer webinar, "The Future of #AI in Research “Is #ChatGPT Smarter than Me?” with #CCAD alumni speakers Shea Andrews and @towfiqueRaj! Registration 🔗 us02web.zoom.us/meeting/regi… #NewVisionResearch #ProfessionalDevelopment
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