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
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.)
What drives the earliest steps of skin cancer development?
In keratinocyte cancers, the first selected mutations almost always hit TP53 and NOTCH genes—plus occasional hits in chromatin remodeling genes or the Hippo pathway.
In keratinocyte cancers, the first selected mutations almost always hit TP53 and NOTCH genes—plus occasional hits in chromatin remodeling genes or the Hippo pathway.
December 2, 2025 at 12:32 AM
What drives the earliest steps of skin cancer development?
In keratinocyte cancers, the first selected mutations almost always hit TP53 and NOTCH genes—plus occasional hits in chromatin remodeling genes or the Hippo pathway.
In keratinocyte cancers, the first selected mutations almost always hit TP53 and NOTCH genes—plus occasional hits in chromatin remodeling genes or the Hippo pathway.
I remain stunned by this finding -- melanocytes have 5x more mutations than keratinocytes, despite the fact that the cells are next to each other in the basal layer of the epidermis, [theoretically] experiencing the same doses of UV radiation.
November 29, 2025 at 5:22 PM
I remain stunned by this finding -- melanocytes have 5x more mutations than keratinocytes, despite the fact that the cells are next to each other in the basal layer of the epidermis, [theoretically] experiencing the same doses of UV radiation.
Nancy Pelosi is retiring after decades of service. I still remember when I received my first R01, and she sent me a congratulatory letter!
November 6, 2025 at 3:49 PM
Nancy Pelosi is retiring after decades of service. I still remember when I received my first R01, and she sent me a congratulatory letter!
What a satisfying mate!
September 30, 2025 at 2:40 PM
What a satisfying mate!
STmut is now working on Visium HD data! Infer copy number from spatial transcriptomics data at unparalleled accuracy and resolution
September 21, 2025 at 3:21 PM
STmut is now working on Visium HD data! Infer copy number from spatial transcriptomics data at unparalleled accuracy and resolution
Does anyone else have dogs that ruin their sleep score? I was all good till 7am, but then an intermittent Mastiff with a HrV of 300 took over
September 20, 2025 at 4:53 AM
Does anyone else have dogs that ruin their sleep score? I was all good till 7am, but then an intermittent Mastiff with a HrV of 300 took over
After clearly saving changes to an NIH RPPR form, the system inevitably gives this warning.
September 18, 2025 at 3:36 PM
After clearly saving changes to an NIH RPPR form, the system inevitably gives this warning.
Politicized research comes and goes, but it always leave behind a legacy of permanent paperwork.
September 4, 2025 at 8:07 PM
Politicized research comes and goes, but it always leave behind a legacy of permanent paperwork.
Shutting down the NIH guide for grants was a bad idea. Sure, the grant postings were redundant with grants.gov, but grants.gov posts ALL grant opportunities across the government. My inbox is now flooded with irrelevant calls from the Department of Labor
August 22, 2025 at 2:20 PM
Shutting down the NIH guide for grants was a bad idea. Sure, the grant postings were redundant with grants.gov, but grants.gov posts ALL grant opportunities across the government. My inbox is now flooded with irrelevant calls from the Department of Labor
The Nature brand is strong. Just came across yet another variant, though I don't think this one is affiliated with Springer
June 23, 2025 at 2:21 PM
The Nature brand is strong. Just came across yet another variant, though I don't think this one is affiliated with Springer
Congressman DeSaulnier and I just solved all of America's problems. Stay tuned for the biggest most beautifulest Bill!
May 29, 2025 at 11:05 PM
Congressman DeSaulnier and I just solved all of America's problems. Stay tuned for the biggest most beautifulest Bill!
25K people at my institution have taken and rated Security Awareness training at my institution. How is it rated 4.16/5? This is 30 minutes of my life (at 1.5X speed) that I will never get back.
May 1, 2025 at 6:49 PM
25K people at my institution have taken and rated Security Awareness training at my institution. How is it rated 4.16/5? This is 30 minutes of my life (at 1.5X speed) that I will never get back.
In summary, we believe that UV radiation will, over decades, damage interfollicular melanocytes, killing off some cells. These cells are replenished from stem cells in the hair bulge. It is a clever adaptation to rejuvenate damaged skin. [10]
February 13, 2025 at 10:50 PM
In summary, we believe that UV radiation will, over decades, damage interfollicular melanocytes, killing off some cells. These cells are replenished from stem cells in the hair bulge. It is a clever adaptation to rejuvenate damaged skin. [10]
Indeed, melanocytes that express LowMut gene expression profiles were enriched in the hair bulge. They could also be found in the interfollicular epidermis, where they were somewhat more abundant near the opening of the hair shaft. [9]
February 13, 2025 at 10:50 PM
Indeed, melanocytes that express LowMut gene expression profiles were enriched in the hair bulge. They could also be found in the interfollicular epidermis, where they were somewhat more abundant near the opening of the hair shaft. [9]
Third, we explored morphologic features, indicating that low mutation burden melanocytes are smaller with fewer dendrites. Others have noted that melanocyte stem cells in the hair bulge share similar morphologic features [7]
February 13, 2025 at 10:50 PM
Third, we explored morphologic features, indicating that low mutation burden melanocytes are smaller with fewer dendrites. Others have noted that melanocyte stem cells in the hair bulge share similar morphologic features [7]
Second, we explored gene expression profiles, indicating that low mutation burden melanocytes occupy a more stem-like state [6]
February 13, 2025 at 10:50 PM
Second, we explored gene expression profiles, indicating that low mutation burden melanocytes occupy a more stem-like state [6]
First, we explored mutational signatures, indicating that low mutation burden melanocytes evade the worst of UV-radiation-induced mutagenesis. [5]
February 13, 2025 at 10:50 PM
First, we explored mutational signatures, indicating that low mutation burden melanocytes evade the worst of UV-radiation-induced mutagenesis. [5]
Most melanocytes in heavily sun exposed skin have high mutation burdens, but we were stunned to see that there is a subpopulation of melanocytes with virtually no mutational damage. [3]
February 13, 2025 at 10:50 PM
Most melanocytes in heavily sun exposed skin have high mutation burdens, but we were stunned to see that there is a subpopulation of melanocytes with virtually no mutational damage. [3]
We have now genotyped ~300 skin cells from over 50 different donors (available in cbioportal and dbgap). Their mutation burdens vary from person to person, site to site within each person, and cell to cell within each site. In this manuscript, we explore the latter source of variability. [2]
February 13, 2025 at 10:50 PM
We have now genotyped ~300 skin cells from over 50 different donors (available in cbioportal and dbgap). Their mutation burdens vary from person to person, site to site within each person, and cell to cell within each site. In this manuscript, we explore the latter source of variability. [2]
How much does a graduate student actually make at UCSF? I am pointed to a byzantine table, in which I am told their efforts fluctuate, depending on classwork. So a 1st year would be somewhere between 32K and 65K? There are further complexities surrounding the entry point.
December 13, 2024 at 7:32 PM
How much does a graduate student actually make at UCSF? I am pointed to a byzantine table, in which I am told their efforts fluctuate, depending on classwork. So a 1st year would be somewhere between 32K and 65K? There are further complexities surrounding the entry point.
But I got one last walk on them!
December 7, 2024 at 6:22 AM
But I got one last walk on them!
Setting these reservations aside, I am a scientist who can be persuaded by evidence. I will try out this place out for awhile, side by side with X, and see how it goes
November 17, 2024 at 11:40 PM
Setting these reservations aside, I am a scientist who can be persuaded by evidence. I will try out this place out for awhile, side by side with X, and see how it goes