Thank you Guillaume!!

Thx for reading thus far, check out the full story now!
nature.com/articles/s4156…
Shout out to the Young Lab and our amazing collaborators Roger Foo, Yuchen Long, Jin Zhu, and Matt Ackers-Johnson. Teamwork makes the dream work 😻 @NUSMedicine @NUS_DBS

We found that ECM ligands and mechanics distinctly regulate fibroblast behavior. And ligands outweigh mechanics in dictating fibroblast activation and rejuvenation. We also predicted ECM- vs biophysical-therapy efficacy with DECIPHER. It’s applicable to other tissue/disease.

DECIPHER: DECellularized In situ Polyacrylamide Hydrogel—Ecm hybRid, enabling independent stiffness tunability while maintaining native ECM composition, architecture, and tissue viscoelasticity, perfect for seeding cells afterwards.

And thankfully, she was super supportive!!🥹 We met the next day and planned everything that needed optimization and everything that might go wrong along the way. A few months later, luckily, it worked very well, and we got many exciting findings from our new system: DECIPHER😆🈶

I couldn’t sleep at all for the rest of the night—but for a different reason. I planned out in my head every experiment needed to test and optimize the idea to see if it works. And I prepared my pitch to Jennifer that I want to change my thesis almost entirely 🥺.

And our lab @jennyoung.bsky.social happens to know enough about polyacrylamide from Engler’s work that we might be able to decouple substrate stiffness in the meantime by controlling the hydrogel recipe ⁉️

This is a fundamentally different decellularization technique from how it’s been done for decades.
We used an interpenetrating polyacrylamide network to stabilize ECM before in situ decellularization. This keeps ECM in their native form (no pulverization or digestion).

I learned it as a polyacrylamide-assisted tissue clearing platform, which removes lipid bilayers to enable whole-organ imaging 🔬. But as my mind ran wild in bed, I wondered—what if we took it a step further and removed cells entirely, instead of just the membranes? 🧐

Structural and molecular interrogation of intact biological systems - Nature High-resolution imaging has traditionally required thin sectioning, a process that disrupts long-range connectivity in the case of brains: here, intact mouse brains and human brain samples have been m...

One night I couldn’t sleep, pondering about my thesis and about this dilemma that me and this field is facing. And a paper that had nothing to do with this somehow came to my mind: CLARITY, developed by the Deisseroth lab at Stanford.
www.nature.com/articles/nat...

Interesting to think about! But we couldn’t find existing biomaterial systems that can answer such questions — classical reconstituted decellularized ECM loses mechanics, while hydrogels lacks mature ECM ligands…🥲

We set out to answer a longstanding question regarding extracellular matrix: is the ECM influencing cells more via ligand biochemistry or mechanobiology?
🧪⚖️💪🏻

Hybrid hydrogel–extracellular matrix scaffolds identify biochemical and mechanical signatures of cardiac ageing - Nature Materials A hybrid extracellular matrix–hydrogel with tunable mechanical stiffness and biochemical composition of young or aged cardiac tissue is used to identify the specific contributions of extracellular mat...

It’s been a long time coming but…
so happy my Ph.D. work (part of) is now published on nature materials 🥳
I remember it all too well about this project, the serendipity and the exciting findings…🧵 @jennyoung.bsky.social @mbisg.bsky.social @BME_NUS @NUS
www.nature.com/articles/s41...

DECIPHER: DECellularized In situ Polyacrylamide Hydrogel—Ecm hybRid, enabling independent stiffness tunability while maintaining native ECM composition, architecture, and tissue viscoelasticity, perfect for seeding cells afterwards.

And thankfully, she was super supportive!!🥹 We met the next day and planned everything that needed optimization and everything that might go wrong along the way. A few months later, luckily, it worked very well, and we got many exciting findings from our new system: DECIPHER😆🈶

I couldn’t sleep at all for the rest of the night—but for a different reason. I planned out in my head every experiment needed to test and optimize the idea to see if it works. And I prepared my pitch to Jennifer that I want to change my thesis almost entirely 🥺.

And our lab @jennyoung.bsky.social happens to know enough about polyacrylamide from Engler’s work that we might be able to decouple substrate stiffness in the meantime by controlling the hydrogel recipe ⁉️

This is a fundamentally different decellularization technique from how it’s been done for decades.
We used an interpenetrating polyacrylamide network to stabilize ECM before in situ decellularization. This keeps ECM in their native form (no pulverization or digestion).

I learned it as a polyacrylamide-assisted tissue clearing platform, which removes lipid bilayers to enable whole-organ imaging 🔬. But as my mind ran wild in bed, I wondered—what if we took it a step further and removed cells entirely, instead of just the membranes? 🧐

Structural and molecular interrogation of intact biological systems - Nature High-resolution imaging has traditionally required thin sectioning, a process that disrupts long-range connectivity in the case of brains: here, intact mouse brains and human brain samples have been m...

One night I couldn’t sleep, pondering about my thesis and about this dilemma that me and this field is facing. And a paper that had nothing to do with this somehow came to my mind: CLARITY, developed by the Deisseroth lab at Stanford.
www.nature.com/articles/nat...

Interesting to think about! But we couldn’t find existing biomaterial systems that can answer such questions — classical reconstituted decellularized ECM loses mechanics, while hydrogels lacks mature ECM ligands…🥲

We set out to answer a longstanding question regarding extracellular matrix: is the ECM influencing cells more via ligand biochemistry or mechanobiology?
🧪⚖️💪🏻

This is figure 1, which shows the role of DNA damage in aging and cancer.

A Review in Nature Aging explores the intersection between cancer and aging, illustrating shared causal mechanisms. https://go.nature.com/4iwNPXK 🔒

In Memoriam: Wolfenson, Giannone, and Schwartz recall the life and many contributions of Michael Sheetz, who passed away on January 30, 2025. rupress.org/jcb/article/...

Proud of this collab! At first, we wondered—why would PIEZO2-positive neurons innervate soft tissue like fat? Turns out, mechanosensation plays a role in unexpected places. Studying PIEZOs keeps revealing surprises in biology and disease! 1/2