Kate O'Donnell
@kateodonnell-lab.bsky.social
Scientist in the Department of Molecular Biology at UT Southwestern Medical Center. We investigate mechanisms of tumorigenesis.
https://labs.utsouthwestern.edu/odonnell-lab
https://labs.utsouthwestern.edu/odonnell-lab
And check out exciting new work from the Oliver lab
@tgoliver.bsky.social showing that KLF4 promotes a KRT13+hillock-like state in squamous lung cancer👇:
www.biorxiv.org/content/10.1...
@tgoliver.bsky.social showing that KLF4 promotes a KRT13+hillock-like state in squamous lung cancer👇:
www.biorxiv.org/content/10.1...
KLF4 promotes a KRT13+ hillock-like state in squamous lung cancer
Lung squamous cell carcinoma (LUSC) is basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumor-propagating cell states in squamous tumors, the broad...
www.biorxiv.org
November 11, 2025 at 6:36 PM
And check out exciting new work from the Oliver lab
@tgoliver.bsky.social showing that KLF4 promotes a KRT13+hillock-like state in squamous lung cancer👇:
www.biorxiv.org/content/10.1...
@tgoliver.bsky.social showing that KLF4 promotes a KRT13+hillock-like state in squamous lung cancer👇:
www.biorxiv.org/content/10.1...
Finally, we are grateful for our funding sources:
DoD, ALA, CPRIT, NCI, Welch Foundation, and V Foundation.
DoD, ALA, CPRIT, NCI, Welch Foundation, and V Foundation.
November 11, 2025 at 6:21 PM
Finally, we are grateful for our funding sources:
DoD, ALA, CPRIT, NCI, Welch Foundation, and V Foundation.
DoD, ALA, CPRIT, NCI, Welch Foundation, and V Foundation.
This work was led by my student Hari Shankar Sunil (who defended his thesis last week and is now officially Dr. Sunil). Special THANKS to all our AMAZING collaborators: Trudy Oliver @tgoliver.bsky.social, Jinming Gao, Tae Hyun Hwang, Ralph DeBerardinis @rjdlab.bsky.social, John Minna, et al.
November 11, 2025 at 6:21 PM
This work was led by my student Hari Shankar Sunil (who defended his thesis last week and is now officially Dr. Sunil). Special THANKS to all our AMAZING collaborators: Trudy Oliver @tgoliver.bsky.social, Jinming Gao, Tae Hyun Hwang, Ralph DeBerardinis @rjdlab.bsky.social, John Minna, et al.
Collectively, our results demonstrate that TMPRSS11B promotes an acidified and immunosuppressive microenvironment. This work also nominates this enzyme as a promising therapeutic target in squamous lung cancer.
November 11, 2025 at 6:21 PM
Collectively, our results demonstrate that TMPRSS11B promotes an acidified and immunosuppressive microenvironment. This work also nominates this enzyme as a promising therapeutic target in squamous lung cancer.
Utilizing ultra-pH-sensitive nanoparticle imaging and in vivo metabolite analysis, we identify regions of acidification, elevated lactate, and enrichment of immunosuppressive macrophages in LUSC tumors.
November 11, 2025 at 6:21 PM
Utilizing ultra-pH-sensitive nanoparticle imaging and in vivo metabolite analysis, we identify regions of acidification, elevated lactate, and enrichment of immunosuppressive macrophages in LUSC tumors.
RNA FISH and spatial transcriptomics in the Rosa26-Sox2-Ires-GfpLSL/LSL; Nkx2-1fl/fl; Lkb1fl/fl (SNL) model reveal an enrichment of Tmprss11b expression in lung squamous tumors (LUSCs), specifically in Krt13+ hillock-like cells.
November 11, 2025 at 6:21 PM
RNA FISH and spatial transcriptomics in the Rosa26-Sox2-Ires-GfpLSL/LSL; Nkx2-1fl/fl; Lkb1fl/fl (SNL) model reveal an enrichment of Tmprss11b expression in lung squamous tumors (LUSCs), specifically in Krt13+ hillock-like cells.
In our new study, we show that TMPRSS11B depletion reduces tumor burden and triggers an infiltration of immune cells in immunocompetent mice.
November 11, 2025 at 6:21 PM
In our new study, we show that TMPRSS11B depletion reduces tumor burden and triggers an infiltration of immune cells in immunocompetent mice.
We initially identified TMPRSS11B in a Sleeping Beauty transposon mutagenesis screen (PMID:30463017). Our prior work showed that TMPRSS11B promotes the transformation of human bronchial epithelial cells and enhances lactate export from human lung squamous cell carcinoma cells.
November 11, 2025 at 6:21 PM
We initially identified TMPRSS11B in a Sleeping Beauty transposon mutagenesis screen (PMID:30463017). Our prior work showed that TMPRSS11B promotes the transformation of human bronchial epithelial cells and enhances lactate export from human lung squamous cell carcinoma cells.
Congratulations Trudy and Abbie, et al! Beautiful work!
September 23, 2025 at 3:56 PM
Congratulations Trudy and Abbie, et al! Beautiful work!
Congratulations Niladri!!
August 29, 2025 at 9:27 PM
Congratulations Niladri!!
Congratulations!!!
August 14, 2025 at 4:16 AM
Congratulations!!!
Congratulations Debbie! Exciting news!
July 18, 2025 at 2:10 PM
Congratulations Debbie! Exciting news!
It was a pleasure to speak to our SURF students - thank you for the invite Dr. Diaz!
July 17, 2025 at 9:48 PM
It was a pleasure to speak to our SURF students - thank you for the invite Dr. Diaz!
A special thanks to ALL our collaborators for their important contributions to this work and to NIH/NCI, CPRIT, V Foundation, Welch Foundation, and DoD for their support, and I’m excited that our submission was selected for the cover (credit: Jose Cabrera)!
July 17, 2025 at 8:57 PM
A special thanks to ALL our collaborators for their important contributions to this work and to NIH/NCI, CPRIT, V Foundation, Welch Foundation, and DoD for their support, and I’m excited that our submission was selected for the cover (credit: Jose Cabrera)!
Collectively, our studies uncover a novel mechanism by which two immune checkpoint proteins are coordinately regulated and suggest a new therapeutic strategy for lung cancer patients.
July 17, 2025 at 8:57 PM
Collectively, our studies uncover a novel mechanism by which two immune checkpoint proteins are coordinately regulated and suggest a new therapeutic strategy for lung cancer patients.
Finally, we showed that ISR activation accelerates tumorigenesis and inhibits T cell function, effects that can be overcome by combining PD-1 and TIGIT blockade with the ISR inhibitor ISRIB.
July 17, 2025 at 8:57 PM
Finally, we showed that ISR activation accelerates tumorigenesis and inhibits T cell function, effects that can be overcome by combining PD-1 and TIGIT blockade with the ISR inhibitor ISRIB.
Our analysis of primary human lung tumors identified a significant correlation between PD-L1 and CD155 expression. This is particularly interesting because other groups have shown that CD155 expression is associated with resistance to anti-PD-1 therapy in lung cancer.
July 17, 2025 at 8:57 PM
Our analysis of primary human lung tumors identified a significant correlation between PD-L1 and CD155 expression. This is particularly interesting because other groups have shown that CD155 expression is associated with resistance to anti-PD-1 therapy in lung cancer.
Here we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. We show that CD155 and PD-L1 are coordinately induced by the ISR, enhancing translation of both immune checkpoints through bypass of inhibitory uORFs in their 5' UTRs.
July 17, 2025 at 8:57 PM
Here we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. We show that CD155 and PD-L1 are coordinately induced by the ISR, enhancing translation of both immune checkpoints through bypass of inhibitory uORFs in their 5' UTRs.
The ISR is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. We previously showed that ISR activation potently induces Programmed Death Ligand 1 (PD-L1), leading to suppression of anti-tumor immunity (Suresh et al, Nature Cancer, 2020).
July 17, 2025 at 8:57 PM
The ISR is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. We previously showed that ISR activation potently induces Programmed Death Ligand 1 (PD-L1), leading to suppression of anti-tumor immunity (Suresh et al, Nature Cancer, 2020).
The Integrated Stress Response (ISR) Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer url: aacrjournals.org/cancerres/ar...
The Integrated Stress Response Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer
The integrated stress response represents a targetable axis to improve the efficacy of immunotherapy in lung cancer by inhibiting the coordinated translational regulation of the PD-L1/PD-1 and CD155/T...
aacrjournals.org
July 17, 2025 at 8:57 PM
The Integrated Stress Response (ISR) Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer url: aacrjournals.org/cancerres/ar...