DMartin

@drddom

Associate Prof at UWaterloo in Biology. Study autophagy & protein lipidation (S-acylation & N-myristoylation) in ALS & Huntington disease. Expect science, food, some cdnpoli, & dog pics (opinions my own)

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DMartin@drddom· Jul 10

I think I might be ready to run a marathon....slowly. But still.

DMartin@drddom· Jun 20

What a week! 5 people from the lab graduated! Congratulations to everyone! Thank you for all you've done for the lab & good luck in the future! You're all going to crush it! Alyssa Guo, BCS Ben Hollingsworth,BSc Kalista Ho, BSc Jessica Lin, BSc Cailyn Perry, MSc @cailyncreative.bsky.social

Collage photo of students at convocation. Top photo is with Alyssa Guo. Middle left is with Ben Hollingsworth, to the right is Cailyn Perry. Bottom photo from left to right is Kalista Ho, Jessica Lin, Cailyn Perry, and me.

DMartin@drddom· Jun 9

My lab on slack.... maybe we can ask for a bigger discount?

DMartin@drddom· Jun 8

What an incredible turnout for @alscanada.bsky.social #WalkToEndALS at @uwaterloo.ca! 250-300 people came to raise funds & awareness for ALS. We hit our target & then some! Thank you to everyone who came out & @waterloosci for all your support! alscanadawalktoendals.als.ca/ontario2026/...

Group photo of the NeurdyPhagy Lab and family standing outside. A goofy looking ginger (me) is taking a selfie with everyone in the background). Everyone is wearing tshirts with the Walk to End ALS logos. Also, my beautiful chunky bulldog Ruby is staring up at me lovingly.

DMartin@drddom· Jun 7

If you do a long run and you don't share with everyone, did you really run? But also, I can't believe 3 physio sessions fixed all my issues (knock on wood). This was my first long run since July 2025 I think. Also also, at what point do you start to think a marathon is doable?

DMartin@drddom· Jun 4

Meet Ruby. The happiest dog in the world! She surgically removed the squeakers from 3 of these stuffies in 30 mins.

DMartin@drddom· Jun 2

Happy Pride Month from Proose (Pride Goose) & the NeurdyPhagy Lab. Again, be proud of who you are!

DMartin@drddom· Jun 2

Happy Pride Month all! Be proud of who you are and enjoy who you are. (Pin by @christineliu.art )

Picture of pin in the shape of a brain colored with the pride rainbow colours. The pin is attached to a bookbag. And there is light shining through a window in the background.

DMartin@drddom· May 21

OK. Trying to verify I am human has reached a new extreme. "Place the pipe to help the capybara reach the other side." Just trying to get some maintenance from @eppendorf.bsky.social Took me longer to prove I'm human than the request.

A screenshot showing an image to verify I am human. It asks the user to "Place the pipe to help the capybara reach the other side." Below that is an image of 3 cartoon characters (Otter, Capybara, rooster) on the left and a pipe looping towards a circle with a space just before the circle. On the far right are 3 pipe options to help fill the blank.

DMartin@drddom· May 20

OK. Now for the pretty version of those muscle cells imaged on the confocal c/o @jesuisyasmeena.bsky.social

DMartin@drddom· May 18

Was feeling bad about being a scientist for the usual reasons (recently rejected papers, grants, etc) & I was coming in on a holiday to feed our patient stem cells we're using to make neuromuscular junctions to study ALS. Today, the muscles twitched! Today I was reminded why I love research!

DMartin@drddom· Apr 21

Only mildly stressful having 2 papers with decisions pending at the same journal.....

DMartin@drddom· Apr 17

Beautiful day for a run alongside the Versailles Palace gardens.

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

DMartin@drddom· Apr 15

Notre Dame was to the left.

DMartin@drddom· Apr 15

How your email finds @drssfs.bsky.social and I.

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

DMartin@drddom· Apr 15

Beautiful day for a run along the Seine and through the Louvre courtyard in Paris.

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.

DMartin@drddom· Apr 13

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!

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.

DMartin@drddom· Apr 8

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

(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.

DMartin@drddom· Apr 8

We previously showed that SQSTM1 (aka p62) was S-acylated & decreased in HD. tinyurl.com/ym9ra6d7 Mutations in the SQSTM1 gene are linked to ALS, frontotemporal dementia & more disease. We wanted to know 1) are other ALS-linked proteins S-acylated 2) are they dysregulated in HD & ALS?

Sequestosome 1 (SQSTM1)/p62 is a receptor for autophagy required to deliver damaged organelles and aggregated proteins to the lysosome for degradation. SQSTM1 undergoes palmitoylation, the reversible addition of the saturated fatty acid palmitate to cysteines. Herein, we show that palmitoylation is significantly reduced in the brains of patients with Huntington disease (HD). The loss of SQSTM1 palmitoylation may be responsible for defective autophagy in HD, wherein cargo is not delivered to lysosomes, providing a novel target for HD.

DMartin@drddom· Apr 8

Regardless of etiology (genetic, environmental, or unknown), protein mislocalization occurs in nearly all neurodegenerative diseases and is one of the earliest events at the protein level. This leads to a toxic gain of function in the wrong location & toxic loss of function at the native site.

TDP-43 in ALS and HD neurodegeneration. Schematic indicating the neurodegenerative process of ALS (top) and HD (bottom). The process of neurodegeneration in ALS focuses on the mislocalization and aberrant aggregation of TDP-43 resulting in the loss of motor neurons with subsequent muscle atrophy. The schematic of HD highlights the aberrant aggregation of mHTT (coaggregated with pTDP-43) and subsequent loss of striatal neurons from the brain. The depletion of neurons within pertinent regions of the brain in HD is indicated on the bottom left. Regardless of the toxicity, or lack thereof, of aggregates, aggregates are an indication of proteostasis deficiency. In our model, we do not imply toxicity but highlight that aggregation is typically a precursor to, or marker of, degeneration that is indicative of proteostasis deficiency.
https://www.jneurosci.org/content/46/10/e0263252026/tab-figures-data

DMartin@drddom· Mar 27

We're all cuddled up now.

DMartin@drddom· Mar 26

Someone is waiting impatiently for the primary human to come home. Sometimes it hurts to be the secondary human....

The most beautiful of bully dogs looks out the window longingly waiting for their favorite human...who is not the person taking the picture. Her face is resting on the windowsill in the most pathetic way.

DMartin@drddom· Mar 22

Wow. This UW student production of Little Shop of Horrors has completely exceeded my expectations. The singing is fantastic & Audrey II is everything you could hope for in a singing, flesh-eating plant! wusa.ca/event/little...

A pamphlet for the Little Shop Of Horrors is held up in front of the stage for said musical. The front of the pamphlet has a picture of flesh-eating, but comical and pitch perfect singing plant that looks like a Venus fly trap

DMartin@drddom· Mar 18

This dog can make any bad day better.

An adorable doggo is belly up on a couch..she has very short fur, chunky thighs and droopy upsidedown lips with a pink snoot. She looks like she's smiling. She's living the dream.

DMartin@drddom· Mar 11

Thrilled to share our recent review in @sfnjournals.bsky.social ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin. Here we discuss links between HD & ALS. Review & cover art come from the multitalented MSc student @cailyncreative.bsky.social tinyurl.com/57y6hjrd

Screenshot from the JNeursci Webpage showing the cover art.

This artwork portrays a fictional person with amyotrophic lateral sclerosis (ALS). Framing their face is a network of neurons that highlights two motor neurons. One neuron extending from the mouth down to the hands symbolizes two of the major motor functions affected by ALS: bulbar and spinal. The second neuron forms from a single tear that represents the fear those with the disease endure. As this neuron extends to the hands, the connection is severed, symbolizing both the disconnect between the brain and muscles caused by neuron death and the determination of those affected not to be defined by their disease. The bound hands emphasize the physical constraints imposed by ALS while the distance between the hands conveys perseverance. Among the wildflowers shown is the blue cornflower, an emblematic symbol of ALS representing hope and resilience. See the review article by Cailyn Perry and Dale Martin for information on mechanistic links between ALS and Huntington's disease. Cover image: Cailyn Perry.

DMartin@drddom· Mar 5

Everyone should start their day this way, so I thought you could all live a bit vicariously through me. Coffee, cuddles, & thesis reading. The rest of the day will probably be downhill from here....

DMartin@drddom· Mar 4

Time to celebrate some wins! New paper out on Biorxiv today & submitted CIHR today! Someone I really respect & an expert in the field told me the last version was too good & important not to submit. Let's hope it at least gets discussed.

DMartin@drddom· Mar 1

Forgot about this CIHR reviewer gem. We showed S-acylation of p62/SQSTM1 was significantly down in Huntington Disease patient brains. Reviewer wasn't convinced >50% reduction was important. S-acylation directs p62 for autophagy. Disrupted autophagy leads to a build up of proteins, a hallmark of HD.

DMartin@drddom· Feb 21

That pout! Ruby doesn't like being excluded from cooking. She still got lots of carrot ends and some celeriac puree. Don't believe that pout.

DMartin@drddom· Feb 18

How do I know there's a bias when I apply for funding? Well, this statement unfortunately still lives rent free in my head. A reviewer for CFI suggested I couldn't hire postdocs at UW. By the time I received this comment, we had 2 PDFs in the lab. 1 is in industry. Other is a CIHR PDF Scholar.