Terry R Suk
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terryrsuk.bsky.social
Terry R Suk
@terryrsuk.bsky.social
Postdoc in the Gate Lab at Northwestern University Abrams Research Center for Neurogenomics | uOttawa and WesternU alumni
Additionally, we are grateful for the immense support from
#ALSCanada, @braincanada.bsky.social, #NSERC, #CIHR, and the many facilities @uottawamed.bsky.social and everyone else involved!
March 28, 2025 at 2:53 PM
This work could not have been done without everyone in the @maximewc.bsky.social lab, all of our colleagues and collaborators, the constructive feedback from the reviewers, and the many discussions at various meetings throughout the years!
March 28, 2025 at 2:53 PM
Finally we find that SUMOylation is correlated with aging and ALS/FTD in the human brain 🧠 This work has unlocked so many new questions that we are excited to explore!
March 28, 2025 at 2:53 PM
Surprisingly we found that blocking TDP-43 SUMOylation at K408 in mice 🐭 causes significant #sexdifferences including cognitive and social impairment in female mice whereas male mice show evidence of motor neuron dysfunction in the spinal cord
March 28, 2025 at 2:53 PM
As #aging is one of the strongest risk factors for neurodegenerative diseases, we hypothesized that the stress of aging depends on effective TDP-43 SUMOylation to protect neurons in the nervous system
March 28, 2025 at 2:53 PM
In neuron cultures 🧫 we find that without SUMOylation at K408, neurons are not able to recover efficiently from cellular stress leading to the accumulation of nuclear TDP-43 recovery bodies
March 28, 2025 at 2:53 PM
Using #CRISPR 🧬we generated a new knock in #mousemodel 🐁 to block SUMOylation at endogenous K408 allowing us to study what happens to TDP-43 when it can no longer be SUMOylated at this site.
March 28, 2025 at 2:53 PM
SUMO2/3 is targeted to lysine K408 on TDP-43’s C-terminal domain, directly neighbouring serine residues characteristically phosphorylated in disease. Interestingly this post-translationally modified region is particularly well conserved in vertebrate species.
March 28, 2025 at 2:53 PM
Indeed, we discovered that TDP-43 is dynamically SUMOylated by SUMO2/3 in the nucleus specifically under stress conditions to aid in protein clearance during recovery from stress.
March 28, 2025 at 2:53 PM
We were interested in trying to understand the mechanisms by which cellular stress regulates #TDP43 and how these pathways may contribute to sporadic forms of neurodegeneration including #ALS and #FTD. We hypothesized that #SUMOylation may play a role.

🔬Here’s what we found:
March 28, 2025 at 2:53 PM