Jeff Carroll, PhD
@jcarroll42.bsky.social
Neuroscientist; Assoc.Prof. at University of Washington; Huntington’s Disease researcher; Army veteran. https://sites.uw.edu/jeffcarr/
Changing transcripts could be good or bad, but if we look at HD people's favorite genes, we see a very striking pattern of rescue when we target intron-1 with an ASO that we don't see if we target downstream:
July 31, 2025 at 6:00 PM
Changing transcripts could be good or bad, but if we look at HD people's favorite genes, we see a very striking pattern of rescue when we target intron-1 with an ASO that we don't see if we target downstream:
Surprisingly, this is the first mouse HTT ASO experiment to show robust transcriptional rescue. If we look at just the mutant mice by bulk RNASeq, a more distal HTT ASO (left) changes exactly two transcripts - one of which is HTT itself. But targeting intron-1 leads to a huge change of transcripts:
July 31, 2025 at 5:59 PM
Surprisingly, this is the first mouse HTT ASO experiment to show robust transcriptional rescue. If we look at just the mutant mice by bulk RNASeq, a more distal HTT ASO (left) changes exactly two transcripts - one of which is HTT itself. But targeting intron-1 leads to a huge change of transcripts:
The ASO targeting intron-1 basically eliminates aggregates while the more downstream one does nothing:
July 31, 2025 at 5:58 PM
The ASO targeting intron-1 basically eliminates aggregates while the more downstream one does nothing:
So, if you search google scholar enough it will just flag you as a bot and then there's absolutely no recourse, nor a human that you can prove you're not a bot. Reminding me we shouldn't be outsourcing such a key academic service to a for profit company that normalized not talking to its customers.
May 21, 2025 at 3:21 PM
So, if you search google scholar enough it will just flag you as a bot and then there's absolutely no recourse, nor a human that you can prove you're not a bot. Reminding me we shouldn't be outsourcing such a key academic service to a for profit company that normalized not talking to its customers.
Exciting update from PTC Therapeutics ! The results from the 24mo PIVOT-HD study look great! Curious if the FDA considers accelerated approval with some kind of ph4 requirement for more post-approval data. Stoked to see *reductions* in NfL over 2 years in HD!
ir.ptcbio.com/static-files...
ir.ptcbio.com/static-files...
May 5, 2025 at 3:43 PM
Exciting update from PTC Therapeutics ! The results from the 24mo PIVOT-HD study look great! Curious if the FDA considers accelerated approval with some kind of ph4 requirement for more post-approval data. Stoked to see *reductions* in NfL over 2 years in HD!
ir.ptcbio.com/static-files...
ir.ptcbio.com/static-files...
Can't believe we're implicitly forcing every person funded by NIH to sign some kind of loyalty pledge to the whims of the worlds dumbest man.
April 24, 2025 at 4:13 PM
Can't believe we're implicitly forcing every person funded by NIH to sign some kind of loyalty pledge to the whims of the worlds dumbest man.
Spent 5 hours and $1100 dollars at the vet convinced this moron had eaten something terrible, only to find out he has a pinched nerve in his spine. Oops.
April 20, 2025 at 12:46 AM
Spent 5 hours and $1100 dollars at the vet convinced this moron had eaten something terrible, only to find out he has a pinched nerve in his spine. Oops.
... In the cerebellum, we found remarkable amounts of transcriptional dysregulation - not surprising since ATN1 is some kind of transcriptional regulatory protein. Human ASO treatment provided really nice protection there as well ...
March 20, 2025 at 2:07 PM
... In the cerebellum, we found remarkable amounts of transcriptional dysregulation - not surprising since ATN1 is some kind of transcriptional regulatory protein. Human ASO treatment provided really nice protection there as well ...
... Very similar deal with pathology - no signs of neurodegeneration (in common with other RED mouse models) but robust aggregate accumulation that's basically totally reversed with ASO treatment...
March 20, 2025 at 2:06 PM
... Very similar deal with pathology - no signs of neurodegeneration (in common with other RED mouse models) but robust aggregate accumulation that's basically totally reversed with ASO treatment...
... Every behavioral phenotype we looked at was just almost perfectly rescued by knocking down mutant, but not wildtype, ATN1. Really remarkable rescue - never seen anything so robust with an ASO treatment ...
March 20, 2025 at 2:05 PM
... Every behavioral phenotype we looked at was just almost perfectly rescued by knocking down mutant, but not wildtype, ATN1. Really remarkable rescue - never seen anything so robust with an ASO treatment ...
Our collaborators at Ionis made us really clean ASOs targeting mouse and human ATN1 so we could see, first, if lowering mutant ATN1 is protective, and if lowering wildtype ATN1 is bad...
March 20, 2025 at 2:01 PM
Our collaborators at Ionis made us really clean ASOs targeting mouse and human ATN1 so we could see, first, if lowering mutant ATN1 is protective, and if lowering wildtype ATN1 is bad...
Very excited to see this study out in the world. We made what is (we think?) the first fully-humanized mouse model of a repeat expansion disorder, DRPLA, by replacing an entire copy of muring Atn1 with human ATN1 with 112 pure CAG repeats...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
March 20, 2025 at 2:00 PM
Very excited to see this study out in the world. We made what is (we think?) the first fully-humanized mouse model of a repeat expansion disorder, DRPLA, by replacing an entire copy of muring Atn1 with human ATN1 with 112 pure CAG repeats...
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Was going to share my angst of the day with ..... stuff. But instead here's my suggested protest music for the day:
March 19, 2025 at 4:41 PM
Was going to share my angst of the day with ..... stuff. But instead here's my suggested protest music for the day:
An amazing talk from Dr. Kejia Wu in David Bakers lab at the @uwproteindesign at this year’s HD therapeutics conference in Palm Springs about her amazing designed proteins that bind intrinsically disordered peptides, including poly glutamine, which she’s working to tune to be selective for long Q’s!
March 1, 2025 at 5:39 PM
An amazing talk from Dr. Kejia Wu in David Bakers lab at the @uwproteindesign at this year’s HD therapeutics conference in Palm Springs about her amazing designed proteins that bind intrinsically disordered peptides, including poly glutamine, which she’s working to tune to be selective for long Q’s!
This was super meaningful- CHDI foundation has had 20 HD therapeutic conferences, which are a highlight of my year, inspiring hope wise. 5 of us have been to all 20 (me and Profs. Yang, Nguyen, Aronin and Bates). The only thing better than more meetings would be not needing them!
March 1, 2025 at 5:25 PM
This was super meaningful- CHDI foundation has had 20 HD therapeutic conferences, which are a highlight of my year, inspiring hope wise. 5 of us have been to all 20 (me and Profs. Yang, Nguyen, Aronin and Bates). The only thing better than more meetings would be not needing them!
If you need some inspirational music for your "Fuck Donald Trump" push to keep doing science next week, this recent album of Woody Guthrie songs done by Dropkick Murphys is amazing. Oh, and Fuck Donald Trump!
February 9, 2025 at 12:40 AM
If you need some inspirational music for your "Fuck Donald Trump" push to keep doing science next week, this recent album of Woody Guthrie songs done by Dropkick Murphys is amazing. Oh, and Fuck Donald Trump!
Oh great these accounts are happening now. I’m a red blooded heterosexual guy, but that’s an anatomically improbable amount of cleavage, no?
December 29, 2024 at 3:01 PM
Oh great these accounts are happening now. I’m a red blooded heterosexual guy, but that’s an anatomically improbable amount of cleavage, no?
So cool for David, UW and institute for protein design! When I got to UW I sent David a cold email with a kooky idea for HD. He got back right away and offered to work with us. Amazing example a humble brilliant guy.
December 16, 2024 at 2:35 PM
So cool for David, UW and institute for protein design! When I got to UW I sent David a cold email with a kooky idea for HD. He got back right away and offered to work with us. Amazing example a humble brilliant guy.
And he was wearing a little hat!
December 6, 2024 at 7:10 PM
And he was wearing a little hat!
excuse the car in the way, but the Rainier was pretty glorious this morning with the rising sun.
December 6, 2024 at 7:04 PM
excuse the car in the way, but the Rainier was pretty glorious this morning with the rising sun.
Direct hits aren't the only way to rattle your brain, the data in the paper say that each year in the NHL is associated with a 34% increased chance of developing CTE, so whatever they're doing is killing their brains.
December 5, 2024 at 1:45 AM
Direct hits aren't the only way to rattle your brain, the data in the paper say that each year in the NHL is associated with a 34% increased chance of developing CTE, so whatever they're doing is killing their brains.
It's a Christmas miracle!
December 4, 2024 at 5:08 PM
It's a Christmas miracle!