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Brett Garabedian

@brettgarabedian

PhD w Jim Paulson at Scripps Research | Building immune therapies aimed at cancer’s sweet spot 🍭 #glycotime | Dabbling in protein degraders #TPD 🎯

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Latest posts by Brett Garabedian @brettgarabedian

28.02.2026 19:50 πŸ‘ 1 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

β€œWe present two platforms, single-cell outlining and transcriptome sequencing (scGOATseq) and GlycoScope…ScGOAT-seq quantifies lectin-accessible glycan states with gene expression, while GlycoScope enables multiplexed in situ co-detection of glycans and proteins in tissues.β€œ #Glycotime

26.02.2026 08:35 πŸ‘ 1 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
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The protease Cathepsin K can debulk the cancer glycocalyx The cancer glycocalyx is characterized by the overexpression of large glycoconjugates, including mucins, proteoglycans, and polysialic acid, which collectively increase glycocalyx thickness and stiffn...

β€œcathepsin K…uniquely degrades cell-surface mucins, proteoglycans, and polysialylated glycoproteins, and…reduces total glycocalyx thickness…a promising starting point for the development of a glycocalyx-debulking enzyme for cancer therapeutics.” #glycotime @carolynbertozzi.bskyverified.social πŸ‘

21.02.2026 15:43 πŸ‘ 6 πŸ” 1 πŸ’¬ 0 πŸ“Œ 0

We used to synchronize arabidopsis germination in the 4C/-20, maybe this will help here

15.02.2026 10:38 πŸ‘ 0 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

thx for the boost! πŸš€

10.02.2026 19:23 πŸ‘ 0 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

Sheddase Targeting Chimeras (SHEDTACs) catalyze membrane target proteolysis https://www.biorxiv.org/content/10.64898/2026.02.06.703938v1

09.02.2026 22:16 πŸ‘ 1 πŸ” 1 πŸ’¬ 0 πŸ“Œ 0

#TargetedProteinDegradation #InducedProximity #MolecularGlue #TPD #eTPD #PROTAC #LYTAC #MoDEA #KineTAC #PROTAB #AbTAC #EpiTAC #REULR #GlueTAC #TICTAC #AUTAC #ATTEC #AUTOTAC #TrogoTAC #RIPR #RIPTAC #AgnoTAC #FragTAC #SHEDTAC

09.02.2026 23:40 πŸ‘ 0 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

This is precisely the direction we are pushing at my company, Ablytx Inc.

If you would like to learn more about what we are building at the company, or ways to become involved, please reach out and say hello!

bg@ablytx.com

Thank you for your time and feedback

09.02.2026 23:40 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

At a high level, SHEDTACs add a third axis to the eTPD toolbox, distinct from proteasomal and lysosomal strategies, and create room to explore new protease-target pairings across disease areas.

09.02.2026 23:39 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

Β· Functionally, enforced LAG3 shedding afforded enhanced TCR signaling beyond checkpoint blockade.
Β· This approach was extended to the non-canonical ADAM10 substrate, PD-1, suggesting induced shedding may be possible even for β€œunnatural” protease-target pairings.

...

09.02.2026 23:39 πŸ‘ 1 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

Β· Using a focused SHEDTAC library, LAG3 shedding was robust across multiple epitope combinations on both LAG3 and ADAM10.
Β· Shedding was rapid and unaffected by perturbations of proteasomal or lysosomal pathways.

...

09.02.2026 23:39 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

As a proof of concept, this study demonstrates induced shedding of the immune checkpoint LAG3 by the sheddase ADAM10 on primary T cells.

some key takeaways...

09.02.2026 23:38 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

While eTPD has enabled new ways to access difficult targets, modern TPD approaches depend on endocytosis and intracellular trafficking. This work illustrates an alternative, more direct route - enforced proteolysis at the plasma membrane.

09.02.2026 23:38 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

SHEDTACs are bispecific antibodies that bring endogenous membrane proteases (sheddases) into proximity with cell-surface targets to catalyze receptor proteolysis (shedding).

09.02.2026 23:37 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

Dear friends and colleagues,

I am excited to share a preprint describing my take on extracellular targeted protein degradation (eTPD) - a proximity modality termed Sheddase-Targeting Chimeras (SHEDTACs).

www.biorxiv.org/content/10.6... πŸ‘€

09.02.2026 23:37 πŸ‘ 14 πŸ” 4 πŸ’¬ 1 πŸ“Œ 1

At a high level, SHEDTACs add a third axis to the eTPD toolbox, distinct from proteasomal and lysosomal strategies, and create room to explore new protease-target pairings across disease areas.

09.02.2026 22:40 πŸ‘ 0 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

Β· Functionally, enforced LAG3 shedding afforded enhanced TCR signaling beyond checkpoint blockade.
Β· This approach was extended to the non-canonical ADAM10 substrate, PD-1, suggesting induced shedding may be possible even for β€œunnatural” protease-target pairings.

...

09.02.2026 22:39 πŸ‘ 1 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

Β· Using a focused SHEDTAC library, LAG3 shedding was robust across multiple epitope combinations on both LAG3 and ADAM10.
Β· Shedding was rapid and unaffected by perturbations of proteasomal or lysosomal pathways.

...

09.02.2026 22:39 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

As a proof of concept, this study demonstrates induced shedding of the immune checkpoint LAG3 by the sheddase ADAM10 on primary T cells.

some key takeaways...

09.02.2026 22:38 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0

While eTPD has enabled new ways to access difficult targets, modern TPD approaches depend on endocytosis and intracellular trafficking. This work illustrates an alternative, direct route - enforced proteolysis at the plasma membrane.

09.02.2026 22:37 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0
LinkedIn This link will take you to a page that’s not on LinkedIn

SHEDTACs are bispecific antibodies that bring endogenous membrane proteases (sheddases) into proximity with cell-surface targets to catalyze receptor proteolysis (shedding).

09.02.2026 22:37 πŸ‘ 0 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0
A word cloud from the titles of ~1100 NSF grants that were terminated. The most frequent words are STEM, ADVANCE, Student, career, and engines.

A word cloud from the titles of ~1100 NSF grants that were terminated. The most frequent words are STEM, ADVANCE, Student, career, and engines.

This a word cloud from the titles of ~1100 terminated NSF grants.

It is hard not to see these grant terminations as an attack on the training of the future United States scientific workforce.

07.02.2026 15:55 πŸ‘ 170 πŸ” 78 πŸ’¬ 10 πŸ“Œ 11
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Time-of-day immunochemotherapy in non-small cell lung cancer: a randomized phase 3 trial - Nature Medicine In this randomized phase 3 trial, patients with treatment-naive stage III–IV nonsmall cell lung cancer who received sintilimab or pembrolizumab in combination with chemotherapy early in the day (befor...

Amazing

Checkpoint blockade dependence on time of day (ToD)

β€œAfter…28.7 months, the median PFS was 11.3 months…in the early ToD group and 5.7 months…in the late ToD group”

07.02.2026 04:34 πŸ‘ 0 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

Congrats, awesome figures and super comprehensive

06.02.2026 05:00 πŸ‘ 2 πŸ” 0 πŸ’¬ 1 πŸ“Œ 0
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Writers and Readers of Sialylation in Immunoregulation in Cancer Sialic acids are the terminal monosaccharides of the glycocalyx that critically shape cell-cell interactions, and are strongly implicated in regulating immune recognition and tissue homeostasis. In ca...

On #WorldCancerDay πŸŽ—οΈ, our review on Writers and Readers of Sialylation in Immunoregulation in Cancer is out today in #JBiolChem:
πŸ”— www.jbc.org/article/S002...

Follow for future experimental glyco-work from the @siglecdude.bsky.social lab πŸ”¬πŸ§« #glycotime

05.02.2026 04:07 πŸ‘ 21 πŸ” 6 πŸ’¬ 1 πŸ“Œ 0

Desialylation potentiating immune escape #Glycotime

β€œWe demonstrate… complement components (IgG, C1q, C4, and C5) and regulators (Factor I, Factor H, and C4bp) are sialylated, and that bacterial… desialylation suppresses complement activation…, thereby enabling complement evasion.”

06.02.2026 03:42 πŸ‘ 0 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
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The time of day for cancer immunotherapy is associated with major outcomes. Early is better. Results from a randomized trial of lung cancer, backs up the importance of our circadian rhythm and immune system
www.nature.com/articles/s41...

02.02.2026 16:10 πŸ‘ 257 πŸ” 72 πŸ’¬ 10 πŸ“Œ 9

#resistandunsubscribe @profgalloway.com πŸ‘

31.01.2026 10:22 πŸ‘ 0 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0

Apple & Google removed ICE tracking apps in their app stores.

TikTok reportedly suppressed videos criticizing ICE & the shooting of Alex Pretti.

Meta blocked Facebook groups tracking ICE & links to a database of agents that the government wants to keep secret.

Big Tech is enabling Trump's regime.

29.01.2026 20:57 πŸ‘ 13481 πŸ” 6103 πŸ’¬ 559 πŸ“Œ 370

qualifying exam shenanigans

29.01.2026 15:21 πŸ‘ 1 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0