I’m genuinely excited about my ISSCR talk! It’s on the 8th for anyone who cares about 3D/organoid models of ALS/FTD Neurodegeneration! And you may see some of our drug screen in organoids! (Also, drop by and say hi, I am super shy and will hide in the tall grass).

I honestly don’t know what more funding to apply for. Before the year is done we’ll have six NIH applications (because that’s what counts for the department), a ton more of foundations, and are a part of a truckload of additional grant proposals. If you want to collaborate let me know!

Here is a link to today’s broadcast of the Noon Show. It was fantastic to be able to discuss our progress with YWHAG syndrome, and how our research came to be - thanks to Andrew Miner’s inspiring effort! open.spotify.com/episode/3q8Y...

I will be on the local Tuscaloosa radio station Catfish 100.1 today for the Noon Show talking about how we started working on YWHAG syndrome, an ultra-rare pediatric neurological disease. www.thenoonshow.com 1 PM CT (6/30) if you’re interested! (Apologies in advance :P)

Very excited for our new paper, now out in @cellcellpress.bsky.social! /🧵 The protein Tau forms intracellular toxic tangles in neurons in Alzheimer’s disease and Tauopathies. Tau pathology slowly spreads from cell-to-cell but the mechanisms are not clear /1 authors.elsevier.com/sd/article/S...

An emergent disease-associated motor neuron state precedes cell death in ALS www.cell.com/cell/fulltex...

Those that know me know: I hate being slow. So our lab pushed hard and fast: 1 preprint, 3 NIH grants and about 20 foundation grants submitted. An organoid atlas in the works, an organoid screen for ALS/FTD that already has hits. But without funding now I have to be slow.

I’m slowly getting more and more irked with a new number being hung over our heads as metrics for preprints.

Here’s a thought: Academia is a lower-stakes game of thrones. The kicker? It’s all the eight season.

I’ll be at the ISSCR in Montreal, and in Lisbon shortly after if you want to talk: - organoids - ALS - drug screens in organoid models of neurodegenerative diseases - nonsense. Let me know!

Zebra fish remain clear only int the larval stage?? I’ll take “What is the Casper Zebrafish strain?”

Hey, look, I’m on a podcast!! youtu.be/J49xoVrznQY?... Great interview by Dr Goyal if you have the patience to listen to me!

Found out that Supertramp’s Breakfast in America album is on Spotify. Playing, well “Breakfast in America”. Twin boys (2), in one voice, pointing at the cover art: - Huge towers!!!

Beer this early in the morning? Don’t mind if I do! (No hops were harmed. Cannot say the same for yeast.)

- Garbage? - No little one. It’s a storm. Thunder. - Fear. - It’s ok, don’t worry. There’s a song for it. To remind us that storms come and go, like a merry-go-round.

Spouse: Hey the girls miss you after all the grants, do you wanna take them to game night? Me: Sure! At game night, random lady: “excuse me, are you single?” Heard her go back and “report”: no the spouse is home with the babies. I don’t think I’m going back to game night.

One of our compounds rescues Neurodegeneration and validation shows it modulates CE splicing! Drug screening for ALS/FTD at full speed!

We’ve got hits!! On our organoid screen for ALS!!!

Apparently baby B loves Celine Dion, but only her French work. Baby A could not care less whether Celine’s heart goes on to the moon or the deep ocean.

Connectomes are cool. That is all.

“Oh there’s a social event today to celebrate all the grants submitted!” Me:

Lessons in pragmatism. Lesson 1: 9yo: I want to go to the Everest one day! 8yo (not looking up, tired of all the nonsense and whimsy): It’s really cold, sis. Lesson 2: 9yo: I wish we had dinosaurs! 8yo: Dinosaurs + people = extinct people.

And now we’re using AI to quantify changes in organoids over time!! All the modern catchphrases, cool science, amaze, amaze!! … Please fund us.

First drug screen in ALS started!!

Ok, so question: we’ve got an amazingly cool thing. But it’s not going to fly without scRNAseq, and we just can’t do any more. It’s ALS based - any ideas of how to get this funded? I do not want to rely on NIH for this one. We haven’t gotten any federal funding yet.

Another LOI rejected. Moving on. (It was cool data though. Soon to be a preprint/manuscript, stay tuned).

Me, doing work far beyond my old PhD thesis. PRC2:

Scoop: NSF has been quietly blocking new funds and grants to four top universities: Duke, Harvard, Princeton, and Yale. Dozens of proposals from PIs at these universities—and their collaborators—have been stuck at the Office of Award Management awaiting finalization for months.

First R01 written! Is it perfect? No. But…

I am constantly in awe of nature. We think we understand some tiny bits of it, and suddenly, there’s a set of consistent, reproducible results that flips your entire worldview upside down. I’m going to go and have a lie down for a bit. Amaze, amaze.

Be me, see a silly joke on the internets. Create a playlist. 2 songs: - Running up that hill - Rolling down that hill. Snicker in anticipation of an impossible challenge: - Girls, whose playlist is this? 9yo: hmm.. 8y (casually): sisyphus.

Will be in Europe in July! Let me know if you’d like to talk about science, organoids, ALS, etc!

“But Joao why share this?” Because if I’m scooped and you guys solve an ultra rare disease and/or ALS I will cheer from the sidelines and buy you a drink. And make it an expensive one. With the little hats.

So there’s no point in advocating open science if you don’t put your money where your mouth is. We’re submitting our first two R01s. - A: mechanisms of cytoskeletal calcium modulation (based on our YWHAG preprint). - B: a stress mechanism on C9 ALS using our organoid atlas.

Submitting two R01s this cycle. Dunno why.

8yo: No, but she couldn’t have seen it because they only found her at 9PM and it’s a contradiction! Me: Yes! And what do say to that?

“Ok, we’re going to go to have a mango smoothie!” Twins (2yo): Mangoes!!! We get there. Twin A is asleep. Me, to twin B: hey twin A is asleep. Twin B: No. Twin A, mangoes. Needs mangoes. Wake up twin A, mangoes!!

Girls vs boys. 2yo girl (ages ago), starting pensive into the distance. - What are you thinking about, little one? - Sunflowers… 2yo boy (just now ), starting pensive into the distance. - What are you thinking about, little one? - Mangoes…

OMG this escalated quickly: "You said “small organoids,” and my internal visual system apparently interpreted that as: “Tiny vulnerable spherical entities navigating an increasingly hostile technological landscape.” Which, to be fair, is also a reasonable description of postdocs." #wow

Hey ChatGPT design a quick cartoon of our wor…. What is this insane cuteness?? Why are they smiling? And adorable? Is that one wearing a lab coat?? Are those two high-fiving???

On my list today: - get out of the house (hey, it’s a big one). - get to work (take nothing for granted). - give an update on our organoid work for ALS FAC/HOP on a cure. Not on the list. - find a phenotype in our AD organoids???

“What is your brother?” (Hoping for a name) “Pretty!!” (In identical twins, is it Narcissism?)

I’ll be at ISSCR in Montreal presenting our work in organoid models of ALS! Let me know if you want to chat!

“Where was the hottest temperature recorded in the US?” - “Death Valley, California.” “What?? How do you know where that is?” - No reason.

We just got some amazing data and I couldn’t stop analyzing and I promise I’ll stop doing science when I stop feeling this curious about everything.

I have no words. Actually I do. Just not today. www.reuters.com/legal/govern...

You know that one kid that raises their hand and says “finished!” before the whole class has even started their work? … … If you can’t see them, you may be them. (I’m not proud of myself here)

Que será Será I guess

Look, you really shouldn’t paint the walls. Baby A: … I need you to understand this, you’re a good boy, and you’re smart, but we paint on paper, ok. Baby A: … I need you to tell me, with words, that you understand. Baby A: You’re my soda pop. … sure.

Wow. What a week. Tuesday? What do you mean, Tuesday?