Alan Ashworth
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View article: Identification of a two-gene biomarker correlated with sensitivity to combined PARP7 inhibition and AHR activation in cancer cells
Identification of a two-gene biomarker correlated with sensitivity to combined PARP7 inhibition and AHR activation in cancer cells Open
PARP7 inhibitors (PARP7i) and AHR agonists (AHRa) can synergistically suppress growth of some cancer cell lines, but not others. Here, we derived a two-gene transcriptional score to predict the synergistic response and characterized the mo…
View article: Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy in vivo
Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy in vivo Open
The COVID-19 pandemic made plain the need for effective antivirals acting on novel antiviral targets, among which viral macrodomains have attracted considerable attention. We recently described AVI-4206 (1), a potent and selective inhibito…
View article: Macrodomain ADP-ribose binding but not ADP-ribosylhydrolase activity is critical for chikungunya virus infection of <i>Aedes</i> mosquitoes
Macrodomain ADP-ribose binding but not ADP-ribosylhydrolase activity is critical for chikungunya virus infection of <i>Aedes</i> mosquitoes Open
Viral macrodomains are promising antiviral targets that counteract host ADP-ribosylation-mediated antiviral responses in mammals. However, their role in dual-host viruses within the mosquito vector is largely unknown. Here, we investigated…
View article: The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2
The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2 Open
SARS-CoV-2 continues to pose a threat to public health. Current therapeutics remain limited to direct acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-rib…
View article: AcrIF11 is a potent CRISPR-specific ADP-ribosyltransferase encoded by phage and plasmid
AcrIF11 is a potent CRISPR-specific ADP-ribosyltransferase encoded by phage and plasmid Open
Phage-encoded anti-CRISPR (Acr) proteins inhibit CRISPR-Cas systems, allowing phage replication and lysogeny maintenance. Most of the Acrs characterized to date are stable stoichiometric inhibitors. While enzymatic Acrs have been character…
View article: Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning
Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning Open
The macrodomain of severe acute respiratory syndrome coronavirus 2 nonstructural protein 3 is required for viral pathogenesis and is an emerging antiviral target. We previously performed an x-ray crystallography–based fragment screen and f…
View article: Identification and Characterization of PLUTO-201, a Novel Long Non-Coding RNA Associated with Poor Outcomes in Prostate Cancer
Identification and Characterization of PLUTO-201, a Novel Long Non-Coding RNA Associated with Poor Outcomes in Prostate Cancer Open
Despite extensive investigation, the factors promoting aggressive prostate cancer are poorly understood. By performing a comprehensive analysis of whole-genome transcriptome data to identify differential expression across 1,567 patients wi…
View article: Supplementary Figure S2 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170)
Supplementary Figure S2 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170) Open
Supplementary Figure S2 shows an example of no loss of H3K36me3 by IHC (A) and loss of H3K36me3 by IHC (B). Images are at 40x power. Of note, the portal did not allow for uploading of a TIFF file alone as a "supplemental data" file, so the…
View article: Supplementary Table S4 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170)
Supplementary Table S4 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170) Open
Supplementary Table S4 is a table showing the representativeness of study participants.
View article: Supplementary Figure S3 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170)
Supplementary Figure S3 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170) Open
Supplementary Figure S3 shows all 8 patients with H3K36me3 IHC analysis. (A) Cohort A: Other Solid Tumor. (B) Cohort B: ccRCC. Images are at 40x power. Of note, the portal did not allow for uploading of a TIFF file alone as a "supplemental…
View article: Supplementary Protocol S1 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170)
Supplementary Protocol S1 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in <i>SETD2</i><i>-</i>Altered Advanced Solid Tumor Malignancies (NCI 10170) Open
Supplementary Protocol S1 shows the entire clinical trial protocol to supplement the Materials and Methods section.
View article: Supplementary Figure 7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 7 is a graphical abstract of how AR regulates MHCI expression in prostate tumor cells.
View article: Supplementary Figure 1 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 1 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 1 shows sgRNA validation and MHCI protein expression on tumor cell lines.
View article: Supplementary Tables 1-7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Tables 1-7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Table S1: List of top 20 significant (p< 0.05) genes from a whole-genome CRISPRi FACS-based screen which increased or decreased MHC Class I expression upon knockdown. Genes that were indicated as common essential by DepMap were removed fro…
View article: Supplementary Figure 5 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 5 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 5 provides in vivo validation of enhanced T cell responses and enhanced tumor control after AR knockdown.
View article: Supplementary Figure 3 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 3 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 3 shows validation of AR binding in MHC regulatory genes of interest +/- AR inhibition with enzalutamide.
View article: Supplementary Figure 6 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 6 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 6 shows clinical data analysis of neoadjuvant androgen axis inhibition in primary prostate cancer as well as expression analysis of AR, MHCI, and IFNG activity in mHSPC clinical samples.
View article: Supplementary Figure 4 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 4 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 4 shows a co-culture of tumor-antigen specific T cell mediated killing of tumor cells +/- AR inhibition or MHCI inhibition.
View article: Supplementary Figure 2 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 2 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 2 demonstrates MHC expression following pharmacologic inhibition of AR and/or ligand withdrawal.
View article: Supplementary Figure 1 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 1 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 1 shows sgRNA validation and MHCI protein expression on tumor cell lines.
View article: Supplementary Figure 3 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 3 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 3 shows validation of AR binding in MHC regulatory genes of interest +/- AR inhibition with enzalutamide.
View article: Supplementary Figure 7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 7 is a graphical abstract of how AR regulates MHCI expression in prostate tumor cells.
View article: Supplementary Figure 4 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 4 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 4 shows a co-culture of tumor-antigen specific T cell mediated killing of tumor cells +/- AR inhibition or MHCI inhibition.
View article: Supplementary Figure 2 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 2 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 2 demonstrates MHC expression following pharmacologic inhibition of AR and/or ligand withdrawal.
View article: Supplementary Figure 5 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 5 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 5 provides in vivo validation of enhanced T cell responses and enhanced tumor control after AR knockdown.
View article: Supplementary Tables 1-7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Tables 1-7 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Table S1: List of top 20 significant (p< 0.05) genes from a whole-genome CRISPRi FACS-based screen which increased or decreased MHC Class I expression upon knockdown. Genes that were indicated as common essential by DepMap were removed fro…
View article: Supplementary Figure 6 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Supplementary Figure 6 from Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer Open
Supplementary Figure 6 shows clinical data analysis of neoadjuvant androgen axis inhibition in primary prostate cancer as well as expression analysis of AR, MHCI, and IFNG activity in mHSPC clinical samples.