Sean A. Misek
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View article: O-mannosylation and protein maturation check-points represent therapeutic opportunities in BRAF fusion protein oncogenesis
O-mannosylation and protein maturation check-points represent therapeutic opportunities in BRAF fusion protein oncogenesis Open
Fusions between protein-coding genes are common oncogenic drivers across cancers, typically pairing a proto-oncogene with partner that does not independently drive cancer. In all therapeutically actionable fusions, the proto-oncogene is th…
View article: Comprehensive structure-function analysis reveals gain- and loss-of-function mechanisms impacting oncogenic KRAS activity
Comprehensive structure-function analysis reveals gain- and loss-of-function mechanisms impacting oncogenic KRAS activity Open
To dissect variant-function relationships in the KRAS oncoprotein, we performed deep mutational scanning (DMS) screens for both wild-type and KRAS G12D mutant alleles. We defined the spectrum of oncogenic potential for nearly all possible …
View article: LGG-29. BEYOND MAPK SIGNALING - GENOME-SCALE CRISPR/CAS9 SCREENS REVEAL NEW TARGETS FOR TREATMENT OF KIAA1549::BRAF-DRIVEN PEDIATRIC LOW-GRADE GLIOMA
LGG-29. BEYOND MAPK SIGNALING - GENOME-SCALE CRISPR/CAS9 SCREENS REVEAL NEW TARGETS FOR TREATMENT OF KIAA1549::BRAF-DRIVEN PEDIATRIC LOW-GRADE GLIOMA Open
Since the KIAA1549::BRAF fusion was discovered as the most common driver of pediatric low-grade glioma (pLGG), it has been hypothesized that the fusion induces oncogenicity through BRAF activation as a result of KIAA1549 replacing the BRAF…
View article: LGG-26. A ROLE FOR BRAF FUSION PARTNERS IN ONCOGENIC SIGNALING
LGG-26. A ROLE FOR BRAF FUSION PARTNERS IN ONCOGENIC SIGNALING Open
t was originally hypothesized that loss of BRAF N-terminal negative regulatory domains, which are deleted in the KIAA1549:BRAF rearrangement, results in constitutive activation of the BRAF kinase. This model suggests that BRAF fusion partn…
View article: Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries
Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries Open
Reducing disparities is vital for equitable access to precision treatments in cancer. Socioenvironmental factors are a major driver of disparities, but differences in genetic variation likely also contribute. The impact of genetic ancestry…
View article: Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade
Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade Open
Metastatic cutaneous melanoma is a fatal skin cancer. Resistance to targeted and immune therapies limits the benefits of current treatments. Identifying and adding anti-resistance agents to current treatment protocols can potentially impro…
View article: DDDR-11. IDENTIFYING NEW VULNERABILITIES TO TARGET PEDIATRIC LOW-GRADE GLIOMA
DDDR-11. IDENTIFYING NEW VULNERABILITIES TO TARGET PEDIATRIC LOW-GRADE GLIOMA Open
Pediatric low-grade gliomas (pLGGs) are the most common solid tumors in children and are associated with devastating lifelong morbidities and mortality. Recent genomic profiling efforts have revealed that these tumors are largely driven by…
View article: Defining the landscape of cancer vulnerabilities that are engendered by germline genetic variation
Defining the landscape of cancer vulnerabilities that are engendered by germline genetic variation Open
View article: Supplemental Figure 2 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma
Supplemental Figure 2 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma Open
To show that MRTF-A localization was dependent on F-actin dynamics, we stimulated SK-Mel-19 cells with 20% FBS to induce stress fiber formation which induced MRTF-A nuclear localization. We also treated SK-Mel-147 cells with latrunculin B …
View article: Data from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma
Data from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma Open
Melanoma is the most dangerous form of skin cancer with the majority of deaths arising from metastatic disease. Evidence implicates Rho-activated gene transcription in melanoma metastasis mediated by the nuclear localization of the transcr…
View article: Misek et al Supplementary Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion
Misek et al Supplementary Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion Open
The effect of CEP-1347 on glioblastoma cell line viability.
View article: Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion
Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion Open
A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that …
View article: Misek et al Supplementary Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion
Misek et al Supplementary Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion Open
The effect of CEP-1347 on glioblastoma cell line viability.
View article: Supplemental Figure 2 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma
Supplemental Figure 2 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma Open
To show that MRTF-A localization was dependent on F-actin dynamics, we stimulated SK-Mel-19 cells with 20% FBS to induce stress fiber formation which induced MRTF-A nuclear localization. We also treated SK-Mel-147 cells with latrunculin B …
View article: Supplemental Figure 1 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma
Supplemental Figure 1 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma Open
The Cancer Genome Atlas (TCGA) cutaneous melanoma dataset was stratified into quartiles based upon expression of indicated genes. Kaplan-Meier plots were generated from the highest (grey) and lowest (black) expressing quartiles. Survival c…
View article: Data from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma
Data from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma Open
Melanoma is the most dangerous form of skin cancer with the majority of deaths arising from metastatic disease. Evidence implicates Rho-activated gene transcription in melanoma metastasis mediated by the nuclear localization of the transcr…
View article: Supplemental Figure 1 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma
Supplemental Figure 1 from Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma Open
The Cancer Genome Atlas (TCGA) cutaneous melanoma dataset was stratified into quartiles based upon expression of indicated genes. Kaplan-Meier plots were generated from the highest (grey) and lowest (black) expressing quartiles. Survival c…
View article: Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion
Data from EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion Open
A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that …
View article: Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries
Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries Open
Reducing disparities is critical to promote equity of access to precision treatments for all patients with cancer. While socioenvironmental factors are a major driver behind such disparities, biological differences also are likely to contr…
View article: LGG-59. Identifying hidden drivers of low-grade glioma tumor growth
LGG-59. Identifying hidden drivers of low-grade glioma tumor growth Open
Genomic drivers of pediatric low-grade gliomas (pLGGs) converge on alterations that activate the MAPK pathway. However, expression of individual driver oncogenes fails to induce tumor formation with high penetrance and, paradoxically, expr…
View article: BRAF Inhibitor Resistance Confers Increased Sensitivity to Mitotic Inhibitors
BRAF Inhibitor Resistance Confers Increased Sensitivity to Mitotic Inhibitors Open
Single agent and combination therapy with BRAF V600E/K and MEK inhibitors have remarkable efficacy against melanoma tumors with activating BRAF mutations, but in most cases BRAF inhibitor (BRAFi) resistance eventually develops. One resista…
View article: Ibrutinib Blocks YAP1 Activation and Reverses BRAF Inhibitor Resistance in Melanoma Cells
Ibrutinib Blocks YAP1 Activation and Reverses BRAF Inhibitor Resistance in Melanoma Cells Open
View article: Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib in NRAS-Mutant Melanoma Cell Lines
Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib in NRAS-Mutant Melanoma Cell Lines Open
The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (≈50% BRAFV600 mutations and ≈30% NRAS mutations). While drugs targeting the MAPK p…
View article: Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells
Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells Open
View article: Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines
Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines Open
The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (∼50% BRAF V600 mutations and ∼30% NRAS mutations). While targeted therapies have y…
View article: E2F1 Drives Breast Cancer Metastasis by Regulating the Target Gene FGF13 and Altering Cell Migration
E2F1 Drives Breast Cancer Metastasis by Regulating the Target Gene FGF13 and Altering Cell Migration Open
In prior work we demonstrated that loss of E2F transcription factors inhibits metastasis. Here we address the mechanisms for this phenotype and identify the E2F regulated genes that coordinate tumor cell metastasis. Transcriptomic profilin…
View article: The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice
The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice Open
The stromal reaction in pancreatic cancer creates a physical barrier that blocks therapeutic intervention and creates an immunosuppressive tumor microenvironment. The Rho/myocardin-related transcription factor (MRTF) pathway is implicated …
View article: The complex of CCG-257081 bound to pirin
The complex of CCG-257081 bound to pirin Open
A series of compounds (including CCG-1423 and CCG-203971) discovered through an MRTF/SRF-dependent luciferase screen has shown remarkable efficacy in a variety of in vitro and in vivo models, including significant reduction o…
View article: Identification of Pirin as a Molecular Target of the CCG-1423/CCG- 203971 Series of Anti-Fibrotic and Anti-Metastatic Compounds
Identification of Pirin as a Molecular Target of the CCG-1423/CCG- 203971 Series of Anti-Fibrotic and Anti-Metastatic Compounds Open
A series of compounds (including CCG-1423 and CCG-203971) discovered through an MRTF/SRF dependent luciferase screen has shown remarkable efficacy in a variety of in vitro and in vivo models, including melanoma metastasis and bleomycin-ind…
View article: Routine Cell Culture v1
Routine Cell Culture v1 Open