Thanks. I was going to respond regardless. I think some of the comments require a response. It was clear that no one had the expertise for S-acylation. But one review should have been reworded. I think people forget that these papers are the work of students & the comments can be devastating.
Thanks. I think it would be easier if the comments were appropriate. I think most of it was addressable with either new experiments or added context. So, I guess we can try to reframe it.
One accepted with revisions. The other brutally rejected. Of course, all I can think about is the rejection.
Take it! Set the precedent! Next time you won't even think about it and it will be directly deposited and it will be a nice surprise.
Thanks! One accepted with minor revisions and the other brutally rejected. :-p
Only mildly stressful having 2 papers with decisions pending at the same journal.....
Forgot to tag my co-I! @mickcraig.bsky.social
Whether you cheered, crawled, or cried, there’s nothing quite like crossing the Boston finish line.
Here are some of those emotional moments. trib.al/lJOYfT2
Sounds cool. Link?
New FeiginLab paper is OUT! A commonly prescribed anti-anxiety drug reduces inflammatory signaling in pancreatic cancer through regulation of cancer-associated fibroblast activity!
aacrjournals.org/cancerrescom...
I thought I was going to miss breakfast. French breakfast supercedes any numerical neuroses.
Also, km. Not miles ;)
Map showing the run route around the Park de Versailles. The path almost looks like a sailboat
Picture beside a man made lake. There are dozens of white row boats docked and lined up along the shore. After that is very well manicured lawn on the proximal side of the lake after the boats. On the other bank are well manicured trees lining the entire lake. There are no people in the image and the water is almost perfectly calm.
A picture of the Palace of Versailles way off in the distance. In the forefront is a very manicured lawn. Next you see a golden fountain emerging from the water. Then there is a large path leading to Versailles lined with trees and statues of Greek Gods. The sun is rising at the top of the picture
Beautiful day for a run alongside the Versailles Palace gardens.
Notre Dame was to the left.
Picture of the River Seine. In the forefront are a bowl of chips and two glasses of wine. In the background is a bridge crossing the river and Parisian buildings
How your email finds @drssfs.bsky.social and I.
Image of the square of the Louvre, which has two glass pyramids; one big and one small. In between the two are a lone couple dressed for a wedding (it's about 8 am on a Wednesday, so I don't think they just got married).
A ginger in a ratty hat with a maple leaf that says Canada and running attire is running along the Seine river. The ginger looks tired.
An image of the Seine taking from the north side of the river. In the forefront is a blurred image of the stonewall that runs along the Seine. In the distant background is the Eiffel tower. There's also an old stone bridge in view with two pillars with golden statues on top.
Beautiful day for a run along the Seine and through the Louvre courtyard in Paris.
New paper from our lab !
Thousands of proteins are targets of a form of post translational lipid attachment known as protein S-acylation, commonly as protein palmitoylation. 23 transmembrane zDHHC enzymes catalyze protein S-acylation in humans.
1/n
www.jbc.org/article/S002...
Two gingers, a PI and a grad student, are standing in front of a screen with a thesis presentation title in the background. They are trying to open a bottle each of sparkling juice and tea in celebration. On the screen you can partially see Cailyn's artwork showing two hands reaching towards one another. One hand is surrounded by Blue Cornflowers, which represent ALS.
An overdue post! Very excited to share that Cailyn Perry @cailyncreative.bsky.social successfully defended her Masters thesis at the end of March! Cailyn's thesis was also nominated for the Dean of Science Award for best thesis! Check out the background art
Congratulations again Cailyn! Great job!
Science is good. We should fund it.
Two identical pictures of Canadian Prime Minister Mark Carney. The first has text: "Shares feel good zoom call with Canadian astronaut as public relations exercise." The second has different text: "Cut's funding for Canadian Space Agency by 32.6%"
A lot of Canucks feel pride at a Canadian astronaut on a moon mission. The Carney government is milking this opportunity to associate itself with those good feelings while cutting nearly a third of all funding for Canada's space agency.
www.canada.ca/en/treasury-...
Carney's cutting science spending, including the development of a Canadian-made lunar rover module.
Wonder if he mentioned that on the call.
Exciting news from our laboratory: UC Irvine receives $12 million to test novel stem cell therapy for Huntington’s disease | UC Irvine School of Medicine share.google/9Z3wiq1dPFk4...
ZDHHC17 Links S-Acylation, Huntington Disease, VCP-associated Multisystem Proteinopathy, and Amyotrophic Lateral Sclerosis. www.biorxiv.org/content/10.64898/2026.04...
ZDHHC17 Links S-Acylation, Huntington Disease, VCP-associated Multisystem Proteinopathy, and Amyotrophic Lateral Sclerosis. www.biorxiv.org/content/10.64898/2026.04...
ZDHHC17 Links S-Acylation, Huntington Disease, VCP-associated Multisystem Proteinopathy, and Amyotrophic Lateral Sclerosis. #NeuroDegeneration 🧪🧠
www.biorxiv.org/content/10.64898/2026.04...
Thanks! By far our biggest paper. 5 labs, 3 disease mouse models, 5 fly lines (plus all their controls), patient cells, and more!
So, in the end, we think ZDHHC17 may have an unappreciated role in ALS!
When we made ZDHHC17 knockdown flies, they died at the pupal stage, but a few partially emerged.
We wanted to know if this was related to the nervous system or motor neurons.
Total nervous system KD was lethal.
Motor neuron KD flies survived, but had a progressive motor deficits!
(A) In healthy neurons wild type HTT is S-acylated (fatty acid represented by red lines) by the protein acyltransferases ZDHHC13 and ZDHHC17 and deacylated by the acyl protein thioesterases APT1 and APT2. In addition to being a substrate of ZDHHC17, HTT also positively modulates the enzymatic activity of ZDHHC17 (indicated by the up arrow beside ‘ZDHHC17’). (B) In an HD neuron, poly-Q expanded mutant HTT (mHTT) is less S-acylated due to reduced interaction with ZDHHC13 and ZDHHC17. In addition, ZDHHC17 activity is lower due to loss of the positive modulatory effect of wild type HTT (indicated by the down arrow beside ‘ZDHHC17’). In contrast, APT1 activity is increased (indicated by the up arrow beside ‘APT1’), likely leading to enhanced deacylation of mHTT. The altered enzymatic activity of these two enzymes, ZDHHC17 and APT1, results in reduced S-acylation of mHTT and other neuronal S-acylated proteins and is associated with mHTT aggregation (green aggregates in the degenerating neuron), cytotoxicity, and ER-Golgi to plasma membrane trafficking deficits. Inhibiting deacylation using the small molecule broad deacylation enzyme inhibitor Palmostatin B (Palm B) and/or the APT1 specific inhibitor ML348 restores S-acylation of HTT and other ZDHHC17 substrates and trafficking deficits, as well as reduces mHTT aggregation and cytotoxicity. Figure created with Biorender.com.
Long story short. Maybe. Our search of S-acylating studies found that ZDHHC17 regulates VCP & TDP-43 localization, but in an S-acylation dependent & independent manner, respectively!
ZDHHC17 is also known as Huntingtin-interacting protein 14 (HIP14) & has been linked to HD.
tinyurl.com/2ytf92rj
C9Orf72 mutations are the primary cause of familial (inherited) ALS. VCP acts like SQSTM1 in autophagy (cell clearance pathway), but it leads to TDP-43 mislocalization in the brain, bones, & muscle (altogether known as multisystem proteinopathy or MSP).
So, is S-acylation a link in HD, ALS & MSP?
