Jeffrey Townsend
@jeffreytownsend.bsky.social
Elihu Professor of Biostatistics @yalesph.bsky.social--Cancer, Infectious disease, Evolutionary biology, Fungi, sometimes running
One of these is the White House @whitehouse-47.bsky.social . The other is Dnipro, Ukraine.
What are the common factors?
What are the common factors?
October 23, 2025 at 5:42 PM
One of these is the White House @whitehouse-47.bsky.social . The other is Dnipro, Ukraine.
What are the common factors?
What are the common factors?
NO KiNGS IN NEW HAVEN
October 18, 2025 at 8:26 PM
NO KiNGS IN NEW HAVEN
NO KiNGS IN NEW HAVEN
October 18, 2025 at 7:53 PM
NO KiNGS IN NEW HAVEN
gave a talk on "Why Cancer Isn’t the Same at Every Age: Lessons for Prevention and Care" at the Joint Retreat on Aging and Cancer Research, sponsored by @yalecancer.bsky.social Program in Genomics, Genetics, and Epigenetics among others including many engaged representatives of the local community.
October 15, 2025 at 9:04 PM
gave a talk on "Why Cancer Isn’t the Same at Every Age: Lessons for Prevention and Care" at the Joint Retreat on Aging and Cancer Research, sponsored by @yalecancer.bsky.social Program in Genomics, Genetics, and Epigenetics among others including many engaged representatives of the local community.
One last point: don't use tobacco.
It causes cancer
doi.org/10.1093/molb...
(also respiratory and pulmonary diseases, cardiovascular and vascular diseases, diabetes mellitus, and reproductive and sexual impairment).
It causes cancer
doi.org/10.1093/molb...
(also respiratory and pulmonary diseases, cardiovascular and vascular diseases, diabetes mellitus, and reproductive and sexual impairment).
October 14, 2025 at 1:07 PM
One last point: don't use tobacco.
It causes cancer
doi.org/10.1093/molb...
(also respiratory and pulmonary diseases, cardiovascular and vascular diseases, diabetes mellitus, and reproductive and sexual impairment).
It causes cancer
doi.org/10.1093/molb...
(also respiratory and pulmonary diseases, cardiovascular and vascular diseases, diabetes mellitus, and reproductive and sexual impairment).
Together, these findings support an interpretation that enhanced ICI response in KRAS G12C-mutant tumors arises from tobacco-driven mutagenesis and its immunogenic consequences, rather than from variant-specific oncogenic or immunologic properties.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
Together, these findings support an interpretation that enhanced ICI response in KRAS G12C-mutant tumors arises from tobacco-driven mutagenesis and its immunogenic consequences, rather than from variant-specific oncogenic or immunologic properties.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
By integrating published clinical outcome data, we have shown that increasing exposure to tobacco predicts lower hazard ratios and higher response rates to immune-checkpoint inhibition.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
By integrating published clinical outcome data, we have shown that increasing exposure to tobacco predicts lower hazard ratios and higher response rates to immune-checkpoint inhibition.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
Our analyses point to the importance of mutagenic context: KRAS G12C is enriched for the tobacco-associated SBS4 mutational signature, which is strongly correlated with tumor mutation burden across lung adenocarcinomas.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
Our analyses point to the importance of mutagenic context: KRAS G12C is enriched for the tobacco-associated SBS4 mutational signature, which is strongly correlated with tumor mutation burden across lung adenocarcinomas.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
To clarify the effect of tobacco-associated mutagenesis, we used data from Litchfield et al. to model the impact of tobacco-driven tumor mutational burden on immune-checkpoint inhibition. Predicted response rates increase sharply at low–moderate exposure to SBS4 (tobacco).
doi.org/10.1016/j.ce...
doi.org/10.1016/j.ce...
October 14, 2025 at 1:07 PM
To clarify the effect of tobacco-associated mutagenesis, we used data from Litchfield et al. to model the impact of tobacco-driven tumor mutational burden on immune-checkpoint inhibition. Predicted response rates increase sharply at low–moderate exposure to SBS4 (tobacco).
doi.org/10.1016/j.ce...
doi.org/10.1016/j.ce...
To clarify the effect of tobacco-associated mutagenesis, we used data from Samstein et al. to model the impact of tobacco-driven tumor mutation burden on immune-checkpoint inhibition outcomes. As SBS4 (tobacco exposure) increases, the predicted hazard ratio declines.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
October 14, 2025 at 1:07 PM
To clarify the effect of tobacco-associated mutagenesis, we used data from Samstein et al. to model the impact of tobacco-driven tumor mutation burden on immune-checkpoint inhibition outcomes. As SBS4 (tobacco exposure) increases, the predicted hazard ratio declines.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Because tobacco smoke exposure contributes to both KRAS G12C mutations and to increased TMB, it follows that KRAS G12C-mutant tumors exhibit significantly increased TMB compared to KRAS G12D tumors.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
Because tobacco smoke exposure contributes to both KRAS G12C mutations and to increased TMB, it follows that KRAS G12C-mutant tumors exhibit significantly increased TMB compared to KRAS G12D tumors.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
Smoking is a major contributor to increased tumor mutational burden in non-small-cell lung cancer. Tobacco smoke-related SBS4-attributed mutation fraction and TMB were significantly correlated across LUAD tumors.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
Smoking is a major contributor to increased tumor mutational burden in non-small-cell lung cancer. Tobacco smoke-related SBS4-attributed mutation fraction and TMB were significantly correlated across LUAD tumors.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
We examined the tobacco mutational signature and KRAS mutation frequency in tumors. KRAS G12C-mutant tumors showed a significantly higher proportion of mutations attributable to the SBS4 tobacco-associated mutational signature compared to KRAS G12D.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
We examined the tobacco mutational signature and KRAS mutation frequency in tumors. KRAS G12C-mutant tumors showed a significantly higher proportion of mutations attributable to the SBS4 tobacco-associated mutational signature compared to KRAS G12D.
authors.elsevier.com/a/1ls3ocYZOi...
authors.elsevier.com/a/1ls3ocYZOi...
We analyzed 9,230 lung adenocarcinoma (LUAD) tumors to assess the mutational context and oncogenic potential of KRAS G12A and G12V and G12C and G12D variants. Their cancer effect sizes were similar—large compared to variants at other sites of KRAS.
aacrjournals.org/cancerres/ar...
aacrjournals.org/cancerres/ar...
October 14, 2025 at 1:07 PM
We analyzed 9,230 lung adenocarcinoma (LUAD) tumors to assess the mutational context and oncogenic potential of KRAS G12A and G12V and G12C and G12D variants. Their cancer effect sizes were similar—large compared to variants at other sites of KRAS.
aacrjournals.org/cancerres/ar...
aacrjournals.org/cancerres/ar...
It has been unclear whether the better outcomes associated with KRAS G12C reflect
• G12C versus G12D allele-intrinsic biology or
• shared dependence on tobacco-induced mutagenesis and elevated tumor mutation burden (TMB).
authors.elsevier.com/a/1ls3ocYZOi...
• G12C versus G12D allele-intrinsic biology or
• shared dependence on tobacco-induced mutagenesis and elevated tumor mutation burden (TMB).
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
It has been unclear whether the better outcomes associated with KRAS G12C reflect
• G12C versus G12D allele-intrinsic biology or
• shared dependence on tobacco-induced mutagenesis and elevated tumor mutation burden (TMB).
authors.elsevier.com/a/1ls3ocYZOi...
• G12C versus G12D allele-intrinsic biology or
• shared dependence on tobacco-induced mutagenesis and elevated tumor mutation burden (TMB).
authors.elsevier.com/a/1ls3ocYZOi...
Just out in Lung Cancer:
KRAS G12C-associated immunotherapy benefit in NSCLC
is substantially mediated by tobacco-induced tumor mutation burden—not allele-specific effects.
authors.elsevier.com/a/1ls3ocYZOi...
KRAS G12C-associated immunotherapy benefit in NSCLC
is substantially mediated by tobacco-induced tumor mutation burden—not allele-specific effects.
authors.elsevier.com/a/1ls3ocYZOi...
October 14, 2025 at 1:07 PM
Just out in Lung Cancer:
KRAS G12C-associated immunotherapy benefit in NSCLC
is substantially mediated by tobacco-induced tumor mutation burden—not allele-specific effects.
authors.elsevier.com/a/1ls3ocYZOi...
KRAS G12C-associated immunotherapy benefit in NSCLC
is substantially mediated by tobacco-induced tumor mutation burden—not allele-specific effects.
authors.elsevier.com/a/1ls3ocYZOi...
🔍 Measuring how fast expression evolves opens a path to understanding how organisms evolve—not just what evolves.
This is just the beginning: from single genes to networks, expression clocks can help decode the tempo of evolution.
doi.org/10.1093/molb...
#MolecularEvolution #GeneExpression #MBE
This is just the beginning: from single genes to networks, expression clocks can help decode the tempo of evolution.
doi.org/10.1093/molb...
#MolecularEvolution #GeneExpression #MBE
July 22, 2025 at 2:42 PM
🔍 Measuring how fast expression evolves opens a path to understanding how organisms evolve—not just what evolves.
This is just the beginning: from single genes to networks, expression clocks can help decode the tempo of evolution.
doi.org/10.1093/molb...
#MolecularEvolution #GeneExpression #MBE
This is just the beginning: from single genes to networks, expression clocks can help decode the tempo of evolution.
doi.org/10.1093/molb...
#MolecularEvolution #GeneExpression #MBE
Some functions are flexible, others are locked down.
Metabolic pathways—like carbon and sulfur metabolism—evolve fast in gene expression.
But core cellular processes like splicing and proteasome function?
They evolve slowly, constrained by essential roles in development.
doi.org/10.1093/molb...
Metabolic pathways—like carbon and sulfur metabolism—evolve fast in gene expression.
But core cellular processes like splicing and proteasome function?
They evolve slowly, constrained by essential roles in development.
doi.org/10.1093/molb...
July 22, 2025 at 2:42 PM
Some functions are flexible, others are locked down.
Metabolic pathways—like carbon and sulfur metabolism—evolve fast in gene expression.
But core cellular processes like splicing and proteasome function?
They evolve slowly, constrained by essential roles in development.
doi.org/10.1093/molb...
Metabolic pathways—like carbon and sulfur metabolism—evolve fast in gene expression.
But core cellular processes like splicing and proteasome function?
They evolve slowly, constrained by essential roles in development.
doi.org/10.1093/molb...
🧪 Next: do fast-changing genes evolve more in protein sequence?
Expression change is positively correlated w/
• amino-acid divergence
• synonymous (dS) & nonsynonymous (dN) divergence
• dN/dS ratio
📈 Evolution in expression and sequence go hand-in-hand—pointing to shared selective pressures
Expression change is positively correlated w/
• amino-acid divergence
• synonymous (dS) & nonsynonymous (dN) divergence
• dN/dS ratio
📈 Evolution in expression and sequence go hand-in-hand—pointing to shared selective pressures
July 22, 2025 at 2:42 PM
🧪 Next: do fast-changing genes evolve more in protein sequence?
Expression change is positively correlated w/
• amino-acid divergence
• synonymous (dS) & nonsynonymous (dN) divergence
• dN/dS ratio
📈 Evolution in expression and sequence go hand-in-hand—pointing to shared selective pressures
Expression change is positively correlated w/
• amino-acid divergence
• synonymous (dS) & nonsynonymous (dN) divergence
• dN/dS ratio
📈 Evolution in expression and sequence go hand-in-hand—pointing to shared selective pressures
🧪 We estimated how long it takes for expression variation to accumulate between sexual development stages (b, e) and asexual spore germination stages (c, f): from ~7 Myr (fastest genes) to ~900 Myr (slowest), most between ~400–900 Myr—a vast heterogeneity in gene expression evolution.
July 22, 2025 at 2:42 PM
🧪 We estimated how long it takes for expression variation to accumulate between sexual development stages (b, e) and asexual spore germination stages (c, f): from ~7 Myr (fastest genes) to ~900 Myr (slowest), most between ~400–900 Myr—a vast heterogeneity in gene expression evolution.
🧪To study how gene expression evolves, we tracked homologous developmental stages of 9 species of Sordariomycetes, including asexual spore germination and sexual development.
Each stage is conserved morphologically—enabling comparison of gene expression shifts across species and time.
Each stage is conserved morphologically—enabling comparison of gene expression shifts across species and time.
July 22, 2025 at 2:42 PM
🧪To study how gene expression evolves, we tracked homologous developmental stages of 9 species of Sordariomycetes, including asexual spore germination and sexual development.
Each stage is conserved morphologically—enabling comparison of gene expression shifts across species and time.
Each stage is conserved morphologically—enabling comparison of gene expression shifts across species and time.
🧪 How fast does gene expression evolve?
A new molecular clock for expression evolution: this study tracked ~4,000 genes across 9 species of fungi . Some genes' expression barely changes in 900M yrs, others shift in just 7M.
doi.org/10.1093/molb...
A new molecular clock for expression evolution: this study tracked ~4,000 genes across 9 species of fungi . Some genes' expression barely changes in 900M yrs, others shift in just 7M.
doi.org/10.1093/molb...
July 22, 2025 at 2:42 PM
🧪 How fast does gene expression evolve?
A new molecular clock for expression evolution: this study tracked ~4,000 genes across 9 species of fungi . Some genes' expression barely changes in 900M yrs, others shift in just 7M.
doi.org/10.1093/molb...
A new molecular clock for expression evolution: this study tracked ~4,000 genes across 9 species of fungi . Some genes' expression barely changes in 900M yrs, others shift in just 7M.
doi.org/10.1093/molb...
No Kings New Haven
June 14, 2025 at 6:35 PM
No Kings New Haven