Hunter Shain
@shainlab.bsky.social
UCSF, Department of Dermatology. Part of HTAN. Cancer, genomics, melanoma, cutaneous squamous cell carcinoma, dermatology, somatic mutations, tumor evolution, spatial transcriptomics, single-cell
More details in our new work:
🔗 www.nature.com/articles/s41...
🔗 www.nature.com/articles/s41...
www.nature.com
December 2, 2025 at 12:32 AM
More details in our new work:
🔗 www.nature.com/articles/s41...
🔗 www.nature.com/articles/s41...
Persistence = more time to accumulate mutations.
Higher mutation rates = higher odds of eventually hitting a growth-promoting driver mutation.
That’s how these early lesions quietly set the stage for full tumor evolution.
Higher mutation rates = higher odds of eventually hitting a growth-promoting driver mutation.
That’s how these early lesions quietly set the stage for full tumor evolution.
December 2, 2025 at 12:32 AM
Persistence = more time to accumulate mutations.
Higher mutation rates = higher odds of eventually hitting a growth-promoting driver mutation.
That’s how these early lesions quietly set the stage for full tumor evolution.
Higher mutation rates = higher odds of eventually hitting a growth-promoting driver mutation.
That’s how these early lesions quietly set the stage for full tumor evolution.
My hypothesis: these early mutations blunt the cell’s ability to undergo apoptosis or repair UV-induced DNA damage.
In a UV-rich environment, such impaired cells simply persist longer.
In a UV-rich environment, such impaired cells simply persist longer.
December 2, 2025 at 12:32 AM
My hypothesis: these early mutations blunt the cell’s ability to undergo apoptosis or repair UV-induced DNA damage.
In a UV-rich environment, such impaired cells simply persist longer.
In a UV-rich environment, such impaired cells simply persist longer.
So what are these early mutations doing?
They appear to create a mutator phenotype.
Keratinocytes with TP53 or NOTCH-pathway mutations carry ~10× more mutations than nearby cells without them.
They appear to create a mutator phenotype.
Keratinocytes with TP53 or NOTCH-pathway mutations carry ~10× more mutations than nearby cells without them.
December 2, 2025 at 12:32 AM
So what are these early mutations doing?
They appear to create a mutator phenotype.
Keratinocytes with TP53 or NOTCH-pathway mutations carry ~10× more mutations than nearby cells without them.
They appear to create a mutator phenotype.
Keratinocytes with TP53 or NOTCH-pathway mutations carry ~10× more mutations than nearby cells without them.
You might expect these early mutations to make cells grow faster.
Surprisingly… they don’t. Mutant clones are no larger than clones without pathogenic mutations.
(This echoes classic findings from Martincorena et al., Science 2015.)
Surprisingly… they don’t. Mutant clones are no larger than clones without pathogenic mutations.
(This echoes classic findings from Martincorena et al., Science 2015.)
December 2, 2025 at 12:32 AM
You might expect these early mutations to make cells grow faster.
Surprisingly… they don’t. Mutant clones are no larger than clones without pathogenic mutations.
(This echoes classic findings from Martincorena et al., Science 2015.)
Surprisingly… they don’t. Mutant clones are no larger than clones without pathogenic mutations.
(This echoes classic findings from Martincorena et al., Science 2015.)
Special thanks to @bishaltandukar.bsky.social @delahnydeivendran.bsky.social who led the study. Also thanks for funding from: the Human Tumor Atlas Network (HTAN), NCI, DOD, @melanomaresearch.bsky.social
November 27, 2025 at 4:11 PM
Special thanks to @bishaltandukar.bsky.social @delahnydeivendran.bsky.social who led the study. Also thanks for funding from: the Human Tumor Atlas Network (HTAN), NCI, DOD, @melanomaresearch.bsky.social
6/ Bottom line:
If you only ask for feedback right before the deadline, you’ll get compliments.
If you ask early and involve people deeply, you’ll get insight.
If you only ask for feedback right before the deadline, you’ll get compliments.
If you ask early and involve people deeply, you’ll get insight.
October 24, 2025 at 8:07 PM
6/ Bottom line:
If you only ask for feedback right before the deadline, you’ll get compliments.
If you ask early and involve people deeply, you’ll get insight.
If you only ask for feedback right before the deadline, you’ll get compliments.
If you ask early and involve people deeply, you’ll get insight.
5/ You can still get critical feedback on a solo grant, but:
Send it early.
Make it clear you want honesty, not reassurance.
Send it early.
Make it clear you want honesty, not reassurance.
October 24, 2025 at 8:07 PM
5/ You can still get critical feedback on a solo grant, but:
Send it early.
Make it clear you want honesty, not reassurance.
Send it early.
Make it clear you want honesty, not reassurance.
4/ If you want real feedback, write a team science proposal together.
Involve your colleague early. Give them some skin in the game — salary support, co-PI status, etc.
That’s when the harsh truths come out — and the proposal actually improves.
Involve your colleague early. Give them some skin in the game — salary support, co-PI status, etc.
That’s when the harsh truths come out — and the proposal actually improves.
October 24, 2025 at 8:07 PM
4/ If you want real feedback, write a team science proposal together.
Involve your colleague early. Give them some skin in the game — salary support, co-PI status, etc.
That’s when the harsh truths come out — and the proposal actually improves.
Involve your colleague early. Give them some skin in the game — salary support, co-PI status, etc.
That’s when the harsh truths come out — and the proposal actually improves.
3/ In hindsight, what else could my colleagues do?
It was too close to the deadline for major changes, and negative feedback that late just feels discouraging.
It was too close to the deadline for major changes, and negative feedback that late just feels discouraging.
October 24, 2025 at 8:07 PM
3/ In hindsight, what else could my colleagues do?
It was too close to the deadline for major changes, and negative feedback that late just feels discouraging.
It was too close to the deadline for major changes, and negative feedback that late just feels discouraging.
2/ Early in my career, I’d send my grant to 5 colleagues the week it was due.
They’d fix a few typos and say it looked “great!”
Then the reviewers would find issues no one else had mentioned.
They’d fix a few typos and say it looked “great!”
Then the reviewers would find issues no one else had mentioned.
October 24, 2025 at 8:07 PM
2/ Early in my career, I’d send my grant to 5 colleagues the week it was due.
They’d fix a few typos and say it looked “great!”
Then the reviewers would find issues no one else had mentioned.
They’d fix a few typos and say it looked “great!”
Then the reviewers would find issues no one else had mentioned.
But there are more! Will be busy for the next few days!
October 9, 2025 at 2:01 PM
But there are more! Will be busy for the next few days!