Brian Doyon
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View article: Supplemental Figure 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Characterization of MC38_sgStk11 mouse model
View article: Supplemental Table 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
10 patients with STK11-deficient solid tumors enrolled in NCT05887492 provided paired biopsies during Phase 1
View article: Supplemental Table 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Peptides that had significantly changed acetylation in response to treatment with either TNG260, entinostat, or vorinostat in pan-acetyl proteomics experiment
View article: Supplemental Figure 9 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 9 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 treatment does not affect proportion of intratumoral Treg cells
View article: Supplemental Table 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 1 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Antibodies and dilutions for western blotting
View article: Supplemental Figure 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 5 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 has the potential for greater therapeutic index than approved HDAC inhibitors
View article: Data from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Data from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Patients with non–small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti–PD-1. In this study, we conducted an in vivo CRISPR screen that identified h…
View article: Supplemental Figure 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 is selective against HDAC3-9, 11
View article: Supplemental Table 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 3 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
CRISPR score results for the comparison of MC38_sgSTK11 tumors in C57BL/6 mice treated with anti-PD-1 compared to MC38_sgSTK11 tumors in athymic nude mice
View article: Supplemental Table 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
CRISPR score results for the comparison of MC38_sgSTK11 tumors to MC38_sgNTC tumors in C57BL/6 mice treated with anti-PD1
View article: Supplemental Figure 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
In-vivo immune sensitizer screen in STK11-isogenic MC38 tumors
View article: Supplemental Figure 7 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 7 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Transcriptomic landscape modulation by TNG260
View article: Supplemental Figure 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 6 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 has a favorable toxicity profile against hematopoietic lineages in vitro
View article: Supplemental Figure 8 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 8 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 increases antigen presentation in STK11-deficient cells
View article: Supplemental Table 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Table 2 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
Antibodies for flow cytometry
View article: Supplemental Figure 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy
Supplemental Figure 4 from TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i>-Mutant Tumors to Anti–PD-1 Immunotherapy Open
TNG260 creates a more active immune microenvironment
View article: Figure S1 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Figure S1 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Figure S1. MAGeCK analysis of CRISPR screens – related to Figure 1. A) Volcano plots showing MAGeCK analysis of CRISPR-Cas9 screens performed in BRCA1 wildtype cancer cell lines, A549 (left) and CAL27 (right). Genes on the le…
View article: Table S3 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Table S3 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Table S3
View article: Figure S4 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Figure S4 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Figure S4. Impact on DNA replication, cell cycle, and apoptosis with PARP inhibitor treatment in BRCA2 wildtype and mutant cells – related to Figure 5. A) Graph showing quantification of % EdU-positive ‘S’ phase cells. DLD-1 …
View article: Table S1 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Table S1 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Table S1
View article: Table S2 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Table S2 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Table S2
View article: Supplementary Data from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Supplementary Data from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Materials
View article: Data from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Data from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
PARP inhibitors (PARPi) are an approved class of anticancer therapeutics that inhibit the activities of PARP1/2 and produce synthetic lethality in BRCA1/2-mutated cancers because of the absence of a functional homologous recombinati…
View article: Figure S2 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Figure S2 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Figure S2. POLB knockout alone does not induce synthetic lethality in cancer cell lines across multiple lineages - related to Figure 2. Viability is not impacted in POLB knockout cells as evidenced by the DepMap Public (Q1 20…
View article: Figure S3 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Figure S3 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Figure S3. Viability with niraparib and olaparib in additional clones – related to Figure 2. A) Immunoblotting analysis of POLB from 2 individual clones confirming POLB knockout in BRCA1 mutant MDA-MB-436 (left) and SUM149PT …
View article: Figure S5 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
Figure S5 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors Open
Supplementary Figure S5. Body weight of the animals is not impacted by the treatment with niraparib – related to Figure 6. A) Effect on body weights of animals containing MDA-MB-436 sgIntron or sgPOLB xenografts treated with vehicle and ni…
View article: TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy
TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy Open
Patients with non–small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti–PD-1. In this study, we conducted an in vivo CRISPR screen that identified histone deacety…
View article: 444 TNG260, a CoREST-selective deacetylase inhibitor, reverses anti-PD1 resistance driven by loss of STK11
444 TNG260, a CoREST-selective deacetylase inhibitor, reverses anti-PD1 resistance driven by loss of STK11 Open
Background Histone deacetylase 1 (HDAC1) was identified from a novel in vivo CRISPR screening platform as a target gene whose inhibition reverses α-PD1 resistance driven by loss of STK11. Histone deacetylases are a well-studied clas…
View article: Consequences of Glycine Mutations in the Fibronectin-binding Sequence of Collagen
Consequences of Glycine Mutations in the Fibronectin-binding Sequence of Collagen Open
Collagen and fibronectin (Fn) are two key extracellular matrix proteins, which are known to interact and jointly shape matrix structure and function. Most proteins that interact with collagen bind only to the native triple-helical form, wh…
View article: The large intracellular loop of hZIP4 is an intrinsically disordered zinc binding domain
The large intracellular loop of hZIP4 is an intrinsically disordered zinc binding domain Open
The human (h) ZIP4 transporter is a plasma membrane protein which functions to increase the cytosolic concentration of zinc.