New research from Memorial Sloan Kettering Cancer Center (MSK) finds skin stem cells retain long-lasting memory of inflammation; shows how a large cancer DNA study could transform personalized oncology; reveals how the protein BAF helps cancer cells hide from the immune system; and investigates how early DNA markings shape cell fate.
Throughout life, skin stem cells continuously regenerate the skin and heal damage.
A new study from the labs of computational biologist Dana Pe’er, PhD , of MSK and stem cell biologist Elaine Fuchs, PhD , of Rockefeller University demonstrates that these stem cells also possess a remarkable form of inflammatory memory that can last over a year.
When skin experiences inflammation, certain regions of the stem cells’ DNA become more accessible. The interdisciplinary research team — led by first authors Christopher Cowley, PhD , Sairaj Sajjath , and Luis Soto-Ugaldi — discovered that some of these accessible regions, called long-term memory domains, remain open for at least a year after the inflammation resolves, even as cells continue to divide to renew the skin. This enables the stem cells to respond faster and more effectively to future inflammation.
By recasting the problem in mathematical terms, and training an AI model to predict which DNA regions retain memory over time, the team was able to pinpoint the sequence features that encode long-term epigenetic memory — meaning heritable changes in gene activity and cell function that persist without altering the underlying DNA sequence. This approach revealed that the genome itself contains instructions that shape methylation and chromatin dynamics, allowing cells to carry information about past inflammation across many generations.
The study suggests that inflammatory memory may help skin adapt to environmental challenges, though persistent changes could also contribute to age-related tissue dysfunction, the researchers note.
This discovery could have implications for understanding how repeated inflammation affects skin aging and disease susceptibility, the researchers say, as the long-lasting epigenetic changes may influence how skin responds to subsequent injuries or environmental stresses. Read more in Science .
Cancer is known to be a disease of genetic mutations, but a new study from MSK is revealing just how complex the connection between mutations and cancer can be. By analyzing the DNA of more than 48,000 cancer patients with almost 450 distinct cancer types, researchers have produced an incredibly detailed map of cancer-causing mutations.
This research was possible because of MSK-IMPACT ® , a tumor sequencing test used to study patients’ tumors and match them with the best therapy for their particular cancer. MSK-IMPACT is also used as research tool, informing studies such as this one.
One significant finding from the study is that the same genetic mutation may behave very differently depending on which type of cancer it appears in. When the mutation occurs in a cancer type in which it’s commonly found, it’s usually a primary trigger of cancer growth: It appears early in tumor development and is found throughout all the tumor cells.
But when same mutation appears in an unexpected cancer type — something that happens about one-third of the time — it tends to arise later, be present in only a portion of tumor cells, and to play a less important role in driving tumor growth. These findings suggest the need for a more nuanced classification system that accounts for cancer type when sequencing results are used to match patients with treatments.
The analysis also revealed important clues about other aspects of cancer genetics, including the role of certain fusion genes in early-onset cancers and the link between genetic ancestry and the likelihood that someone will respond to an immunotherapy like T cell receptor (TCR) therapy .
The co-corresponding authors of the paper were geneticists Chaitanya Bandlamudi, PhD , and Michael Berger, PhD . All the data from this dataset is publicly available through MSK’s cBioPortal for Cancer Genomics . Read more in Cancer Cell .
Chromosomal instability is a common feature of cancer, causing cells to incorrectly divide their chromosomes and form micronuclei — small, defective, mini-nuclei that can signal a dangerous abnormality and trigger an immune response when they rupture.
A new study from the lab of John Maciejowski, PhD , at MSK’s Sloan Kettering Institute identifies a protein called BAF (barrier-to-autointegration factor) as a key player that helps unstable cancer cells hide from this immune detection.
The research — led by Yanyang Chen, PhD , a former graduate student in the lab and postdoctoral researcher Roshan Xavier Norman, PhD — reveals how BAF protects cancer cells by controlling an enzyme called TREX1, which breaks down the errant DNA.
When micronuclei break open, BAF covers the exposed DNA and recruits TREX1 to the site. At the same time, BAF prevents TREX1 from breaking down the DNA too aggressively.
When researchers removed BAF from cancer cells, the DNA-sensing protein cGAS gained greater access to the exposed DNA, triggering a stronger immune response. Loss of TREX1 on top of BAF removal amplified this response further, demonstrating that TREX1 continues to suppress immune activation even when BAF is absent.
The findings suggests that chromosomally unstable cancer cells depend on BAF to keep signals below the threshold that would attract an immune attack. Therefore, targeting BAF could present a potential therapeutic vulnerability by unmasking cancer cells to the immune system. Read more in Molecular Cell .
Every cell in the human body carries identical DNA, yet a neuron and a muscle cell look and behave nothing alike. This distinction arises because different cell types activate different subsets of genes. A critical mechanism governing this selective gene activation involves short DNA sequences called “enhancers” — regulatory elements that function like molecular switches, directing cells toward specific identities by controlling which genes are turned on or off.
Enhancers are embedded within a complex of DNA and proteins known as chromatin, which can be chemically modified to influence gene accessibility. A fundamental question in developmental biology has been whether these regulatory switches are programmed in advance — established early in embryonic development as a kind of genetic blueprint — or whether they only acquire their functional identity as cells progressively specialize.
To investigate this, a multicenter research team led by scientists at the Sloan Kettering Institute examined whether human embryonic stem cells (ESCs) already harbor chromatin regions primed for future activation. ESCs are uniquely suited for this type of research because of their pluripotency — their inherent capacity to develop into any cell type in the body. Employing technologies including CRISPR-based chromatin interrogation, single-cell sequencing, and chromatin profiling, the researchers demonstrated that enhancers associated with mature, specialized cells are indeed pre-marked within ESCs long before differentiation occurs.
These “pre-enhancers” bear distinct molecular signatures detectable throughout the genome. Crucially, because these regions can initiate gene expression independent of external differentiation signals, scientists can potentially exploit them to activate master regulatory genes — effectively steering ESCs toward becoming specific mature cell types on demand.
“These findings introduce a new framework for understanding how pluripotent cells pre-configure their regulatory potential,” says co-corresponding author Julian Pulecio, PhD , a senior research scientist in the Danwei Huangfu Lab . “By revealing chromatin features that predict adult-tissue enhancers, this work opens new opportunities to model gene regulation, improve in vitro cellular reprogramming strategies, and better understand how regulatory elements may become misused in diseases such as cancer.”
Read more in Cell Genomics .