DMartin

@drddom.bsky.social

648 Followers 368 Following

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) https://neurdyphagylab.squarespace.com/

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.

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.

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.

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.

Video depicts human muscle cells. The image is in gray scale. The cells are long and spindly. As the video progresses it shows different views of the cells and the cells are slowly contracting and relaxing. It's really cool.

Map showing the run route around the Park de Versailles. The path almost looks like a sailboat

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

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).

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.

(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.

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.

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

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.

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

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

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.

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.