Joseph Castellano

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

[Joseph Castellano @JM_Castell]

Our study is out! TIMP2, prev tied to blood-borne revitalization of aged brain, regulates hippocampal plasticity via extracell. matrix. Great teamwork f/ 1st-auth @AnaOF, +@Brittany_Hemmer, @Philippi_Sarah, Alex Perales, + more!
https://t.co/RQwUfUoyA3

https://t.co/et3mQoIxPg

[CCAD @The_CCAD]

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 ➡️ https://t.co/fopUj1ftbC

[CCAD @The_CCAD]

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 ➡️ https://t.co/fopUj1ftbC

[Friedman Brain Institute @SinaiBrain]

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 👉 https://t.co/2p8ydIk6ce

[Erik Musiek @ErikMusiek]

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!
https://t.co/AYnP0sCbGj

[Erik Musiek @ErikMusiek]

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. https://t.co/q0ggsUBRco

[Joseph Castellano @JM_Castell]

@ErikMusiek @Jjiyeon_lee @NatureAging Congrats, Erik - exciting work!

[Joseph Castellano @JM_Castell]

@BrainBody_Lab @NIH @ScottRussoPhD @EricJNestler @SwirskiLab @cam_phd @PaulKennyPhD That's great news- congrats, Abha!🎉

[Joseph Castellano @JM_Castell]

@JGrutzendler Congrats on this fantastic study!

[Joseph Castellano @JM_Castell]

@jonykipnis Sorry to hear, Jony! Wishing them safety and strength.

[Joseph Castellano @JM_Castell]

@panagiog @brittany_hemmer Thanks!😀

[Joseph Castellano @JM_Castell]

Excited to share a new preprint out from the lab (https://t.co/RYFJZh3gA1) by 1st-author @brittany_hemmer , a newly minted PhD from the lab! A brief thread on what we found (1/n):

[Joseph Castellano @JM_Castell]

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).

[Joseph Castellano @JM_Castell]

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)

[Joseph Castellano @JM_Castell]

@panagiog @BrittanyHemmer Thanks, Georgia!

[Joseph Castellano @JM_Castell]

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)

[Joseph Castellano @JM_Castell]

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)