Pablo Tamayo

Activated ATF6α is a hepatic tumour driver restricting immunosurveillance

Xin Li, Cynthia Lebeaupin, Aikaterini Kadianaki, Clementine Druelle-Cedano et autres

Abstract Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality and there are limited therapies 1 . Although endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR transducer ATF6α remains …

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OTHR-12. Multi-omics and Functional Precision Medicine for Newly Diagnosed and Recurrent Pediatric Central Nervous System Tumors

John R Crawford, Yan Yuen Lo, Meghana S. Pagadala, Owen S. Chapman et autres

Abstract Comprehensive molecular characterization of pediatric brain tumors has led to more refined diagnoses. However, the feasibility of performing multi-omic and functional precision medicine approaches using ex-vivo drug screening in the clinical setting was previously unknown. Patients with newly diagnosed or recurrent …

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Data driven refinement of gene expression signatures for enrichment analysis

Alexander T. Wenzel, Farhoud Faraji, Kuniaki Sato, Kwat Medetgul-Ernar et autres

Abstract Gene set enrichment methods measure biological process or pathway activation in gene expression data by testing coordinate up- or down-regulation of pathway members in a ranked list of genes. These methods rely on curated, annotated gene sets whose members’ coordinate expression …

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Profiling ranked list enrichment scoring in sparse data elucidates algorithmic tradeoffs

Alexander T. Wenzel, John Jun, Pablo Tamayo, Jill P. Mesirov

Abstract Gene Set Enrichment Analysis (GSEA) is a method for quantifying pathway and process activation in groups of samples, and its single sample version (ssGSEA) scores activation using mRNA abundance in a single sample. GSEA and ssGSEA were developed for “bulk” samples …

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Deciphering the Functional Roles of Individual Cancer Alleles Across Comprehensive Cancer Genomic Studies

Jiayan Ma, Stephanie Ting, Bartholomew Tam, Timothy V. Pham et autres

Cancer genome data has been growing in both size and complexity, primarily driven by advances in next-generation sequencing technologies, such as Pan-cancer data from TCGA, ICGC, and single-cell sequencing. Yet, discerning the functional role of individual genomic lesions remains a substantial challenge …

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Gαs is dispensable for β-arrestin coupling but dictates GRK selectivity and is predominant for gene expression regulation by β2-adrenergic receptor

Valeria Burghi, Justine S. Paradis, Sendi Rafael Adame-Garcia, Xingyu Wu et autres

β-arrestins play a key role in G protein–coupled receptor (GPCR) internalization, trafficking, and signaling. Whether β-arrestins act independently of G protein–mediated signaling has not been fully elucidated. Studies using genome-editing approaches revealed that whereas G proteins are essential for mitogen-activated protein kinase …

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Targeting macrophage Syk enhances responses to immune checkpoint blockade and radiotherapy in high-risk neuroblastoma

Deepak Rohila, In Hwan Park, Timothy V. Pham, Riley N. Jones et autres

Background Neuroblastoma (NB) is considered an immunologically cold tumor and is usually less responsive to immune checkpoint blockade (ICB). Tumor-associated macrophages (TAMs) are highly infiltrated in NB tumors and promote immune escape and resistance to ICB. Hence therapeutic strategies targeting immunosuppressive TAMs …

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Association of adaptive immunity/inflammatory genes with survival in prostate cancer.

Austin B. Hopper, Harris Benjamin Krause, Andrew Elliott, Alex Patrick Farrell et autres

5022 Background: Advances in immunotherapy have had little impact in prostate cancer (PCA). We have previously examined the immune microenvironment in both localized and metastatic PCA and found that primary PCA shows local inflammation/adaptive immunity whereas metastatic disease shows a shift towards …

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Abstract 3246: Targeting Syk reprograms tumor-associated macrophages and enhances responses to immune checkpoint blockade and radiation therapy in high-risk neuroblastoma

Deepak Rohila, In Hwan Park, Timothy V. Pham, Riley N. Jones et autres

Abstract Neuroblastoma (NB) is the most common extracranial solid malignancy in children. As leading regulators of inflammation and tumor progression, tumor associated macrophages (TAMs) have gained major interest as immunotherapeutic targets in NB. Hence targeting or “re-educating” tumorigenic macrophages towards an immunostimulatory …

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Abstract 4281: Data driven refinement of gene signatures for enrichment analysis and cell state characterization

Alexander T. Wenzel, Pablo Tamayo, Jill P. Mesirov

Abstract The use of gene expression data has been crucial to the functional characterization of changes in molecular pathway activity and for identifying targets for novel treatments. However, the interpretation of this data is complicated by its high dimensionality and the difficulty …

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Association of Adaptive Immunity/Inflammatory Genes with Survival in Prostate Cancer

Austin B. Hopper, Harris Benjamin Krause, Andrew Elliott, Alex Patrick Farrell et autres

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721P Molecular alterations as predictors of response to immunotherapy in hepatocellular carcinoma

Jong Wook Chang, Kathryn J. Fowler, S. Ting, Pablo Tamayo et autres

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