John T. Poirier
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View article: Cross-species analysis identifies genotype-driven vulnerabilities in lung adenocarcinoma
Cross-species analysis identifies genotype-driven vulnerabilities in lung adenocarcinoma Open
While three major genetic alteration subsets, characterized by mutations in STK11, KRAS , and EGFR , are seminal in driving tumorigenesis in LUAD, their distinct effects on tumor cells and the tumor microenvironment are not fully understoo…
View article: Deep mutational scanning reveals EGFR mutations conferring resistance to the 4th-generation EGFR tyrosine kinase inhibitor BLU-945
Deep mutational scanning reveals EGFR mutations conferring resistance to the 4th-generation EGFR tyrosine kinase inhibitor BLU-945 Open
Fourth-generation EGFR tyrosine kinase are in development to overcome common resistance mutations. We performed deep mutational scanning (DMS) of the EGFR kinase domain in the context of L858R by introducing a saturation library of ~17,000…
View article: An enhanced Eco1 retron editor enables precision genome engineering in human cells without double-strand breaks
An enhanced Eco1 retron editor enables precision genome engineering in human cells without double-strand breaks Open
Retrons are a retroelement class found in diverse prokaryotes that can be adapted to augment CRISPR–Cas9 genome engineering technology to efficiently rewrite short stretches of genetic information in bacteria and yeast. However, efficiency…
View article: A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist
A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist Open
Interferons (IFNs) play a crucial role in the regulation and evolution of host–virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence Se…
View article: An enhanced Eco1 retron editor enables precision genome engineering in human cells without double-strand breaks
An enhanced Eco1 retron editor enables precision genome engineering in human cells without double-strand breaks Open
Retrons are a retroelement class found in diverse prokaryotes that can be adapted to augment CRISPR-Cas9 genome engineering technology to efficiently rewrite short stretches of genetic information in bacteria and yeast. However, efficiency…
View article: ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1-mutant lung cancer
ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1-mutant lung cancer Open
Inactivating mutations in LKB1/STK11 are present in roughly 20% of nonsmall cell lung cancers (NSCLC) and portend poor response to anti-PD-1 immunotherapy. Unexpectedly, we found that LKB1 deficiency correlated with elevated tumor mutation…
View article: Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in <i>KEAP1</i> mutant lung cancer
Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in <i>KEAP1</i> mutant lung cancer Open
Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed …
View article: 228P SMARCA4 inactivation drives aggressiveness in STK11/KEAP1 co-mutant lung adenocarcinomas through the induction of TGFβ signaling
228P SMARCA4 inactivation drives aggressiveness in STK11/KEAP1 co-mutant lung adenocarcinomas through the induction of TGFβ signaling Open
Even if the development of targeted therapies in lung adenocarcinomas (LUADs) has improved outcomes in patient subsets, intra-driver genetic heterogeneity underlies the diversity of patient responses to such therapies, dramatically impacti…
View article: A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist
A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist Open
Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SA…
View article: First-in-human imaging with [<sup>89</sup>Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumors of the lung and prostate
First-in-human imaging with [<sup>89</sup>Zr]Zr-DFO-SC16.56 anti-DLL3 antibody in patients with high-grade neuroendocrine tumors of the lung and prostate Open
SUMMARY Background Delta-like ligand 3 (DLL3) is aberrantly expressed on the cell surface in many neuroendocrine cancers including small cell lung cancer (SCLC) and neuroendocrine prostate cancer (NEPC). Several therapeutic agents targetin…
View article: Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma
Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma Open
Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive …
View article: KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance
KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance Open
View article: Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in<i>KEAP1</i>mutant lung cancer
Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in<i>KEAP1</i>mutant lung cancer Open
Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We have previously shown that KEAP1 muta…
View article: Clinical Benefit From Immunotherapy in Patients With SCLC Is Associated With Tumor Capacity for Antigen Presentation
Clinical Benefit From Immunotherapy in Patients With SCLC Is Associated With Tumor Capacity for Antigen Presentation Open
View article: Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells
Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells Open
View article: <i>In vivo</i>metabolomics identifies CD38 as an emergent vulnerability in<i>LKB1</i>-mutant lung cancer
<i>In vivo</i>metabolomics identifies CD38 as an emergent vulnerability in<i>LKB1</i>-mutant lung cancer Open
LKB1/STK11 is a serine/threonine kinase that plays a major role in controlling cell metabolism, resulting in potential therapeutic vulnerabilities in LKB1-mutant cancers. Here, we identify the NAD + degrading ectoenzyme, CD38, as a new tar…
View article: Supplementary Fig 5 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers
Supplementary Fig 5 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers Open
Supplementary Fig 5
View article: Supplementary Fig 4 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers
Supplementary Fig 4 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers Open
Supplementary Fig 4
View article: Supplementary Tables from <i>Rlf–Mycl</i> Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer
Supplementary Tables from <i>Rlf–Mycl</i> Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer Open
Tables S1 - S3
View article: Supplementary Data from Upregulation of <i>MMP-2</i> by HMGA1 Promotes Transformation in Undifferentiated, Large-Cell Lung Cancer
Supplementary Data from Upregulation of <i>MMP-2</i> by HMGA1 Promotes Transformation in Undifferentiated, Large-Cell Lung Cancer Open
Supplementary Data from Upregulation of MMP-2 by HMGA1 Promotes Transformation in Undifferentiated, Large-Cell Lung Cancer
View article: Supplementary Figures from Multiomic Analysis of Lung Tumors Defines Pathways Activated in Neuroendocrine Transformation
Supplementary Figures from Multiomic Analysis of Lung Tumors Defines Pathways Activated in Neuroendocrine Transformation Open
Supplemental figures and figure legends.
View article: Figure S1 from Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses <i>NF2</i> Loss–Driven Tumorigenesis
Figure S1 from Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses <i>NF2</i> Loss–Driven Tumorigenesis Open
Figure S1 related to Figure 1 shows that MLN4924 reduces oligo-ubiquitylation of Lats2 and that Merlin-mutant schwannoma cells have a lower on-target sensitivity to MLN4924 than a genetically matched Merlin-positive Schwann line. Also show…
View article: Data from Lineage Reversion Drives WNT Independence in Intestinal Cancer
Data from Lineage Reversion Drives WNT Independence in Intestinal Cancer Open
The WNT pathway is a fundamental regulator of intestinal homeostasis, and hyperactivation of WNT signaling is the major oncogenic driver in colorectal cancer. To date, there are no described mechanisms that bypass WNT dependence in intesti…
View article: Supplementary Fig 6 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers
Supplementary Fig 6 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers Open
Supplementary Fig 6
View article: Table S2 from Lineage Reversion Drives WNT Independence in Intestinal Cancer
Table S2 from Lineage Reversion Drives WNT Independence in Intestinal Cancer Open
Oligonucleotides
View article: Figure S1 from Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses <i>NF2</i> Loss–Driven Tumorigenesis
Figure S1 from Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses <i>NF2</i> Loss–Driven Tumorigenesis Open
Figure S1 related to Figure 1 shows that MLN4924 reduces oligo-ubiquitylation of Lats2 and that Merlin-mutant schwannoma cells have a lower on-target sensitivity to MLN4924 than a genetically matched Merlin-positive Schwann line. Also show…
View article: Supplementary Fig 1 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers
Supplementary Fig 1 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers Open
Supplementary Fig 1
View article: Data from <i>Rlf–Mycl</i> Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer
Data from <i>Rlf–Mycl</i> Gene Fusion Drives Tumorigenesis and Metastasis in a Mouse Model of Small Cell Lung Cancer Open
Small cell lung cancer (SCLC) has limited therapeutic options and an exceptionally poor prognosis. Understanding the oncogenic drivers of SCLC may help define novel therapeutic targets. Recurrent genomic rearrangements have been identified…
View article: Supplementary Figures from Lineage Reversion Drives WNT Independence in Intestinal Cancer
Supplementary Figures from Lineage Reversion Drives WNT Independence in Intestinal Cancer Open
Supplementary Figures 1-16
View article: Supplementary Fig 4 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers
Supplementary Fig 4 from HER2-Mediated Internalization of Cytotoxic Agents in <i>ERBB2</i> Amplified or Mutant Lung Cancers Open
Supplementary Fig 4