Laura M. Doherty

Abstract 495: Single-cell multiomic drug response profiling of PRISM-multiplexed cancer cell lines sequenced with SBX.

Houlin Yu, Guoping Wang, Stephanie J. Yaung, Heejo Choi et autres

Abstract Inter-individual variability in drug response is a key challenge in precision oncology. Despite recent breakthroughs in targeting RAS-mutant cancers, clinical responses remain heterogeneous. To systematically dissect the molecular determinants of drug sensitivity and resistance, we implemented a high-throughput single-cell multi-omic profiling …

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Abstract 2930: Unraveling determinants of drug response: PRISM viability profiling of hundreds of oncology therapeutics reveals mediators of selectivity and mechanism.

Matthew G. Rees, Mustafa Kocak, Matthew J. Emmett, Colleen T. Harrington et autres

Abstract Incomplete understanding of drug mechanism, selectivity, and polypharmacology can contribute to failed clinical trials. Drug candidates are generally characterized with limited pre-clinical tools and a narrow indication focus based on expected target biology. Using approaches such as large-scale PRISM profiling of …

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Abstract 4502: Expanding the PRISM platform: Addition of new hematologic models and a 10-day assay improve drug sensitivity mapping for epigenetic targets.

Colleen T. Harrington, Antonella Masciotti, Ursula Widocki, Laura M. Doherty et autres

Abstract Despite major advances in targeted therapies, cancer remains a leading cause of death among pediatric, adolescent, and adult populations, emphasizing the need for continued therapeutic innovation. The PRISM assay enables large-scale evaluation of oncology agents by barcoding and pooling over 900 …

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Deubiquitinating Enzymes

Xiaoxi Liu, Laura M. Doherty, Alejandra Felix, Sara J. Buhrlage

The Ubiquitin Proteosome system and its role in protein homeostasis has been a focus of research efforts since it was first discovered. A less studied aspect of the UPS are the deubiquitinating enzymes (DUBs) responsible for reversing ubiquitination. In recent years, interest …

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Virally mediated mechanisms of HLA class I loss in Merkel cell carcinoma and implications for viral epitope presentation

Derin B. Keskin, Patrick Lee, Susan Klaeger, Phuong M. Le et autres

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Reversal of viral and epigenetic HLA class I repression in Merkel cell carcinoma

Patrick C. Lee, Susan Klaeger, Phuong M. Le, Keegan D. Korthauer et autres

Cancers avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I antigen presentation. Merkel cell carcinoma (MCC) is an aggressive, HLA-I-low, neuroendocrine carcinoma of the skin often caused by the Merkel cell polyomavirus (MCPyV). Through the characterization of …

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Integrating multi-omics data reveals function and therapeutic potential of deubiquitinating enzymes

Laura M. Doherty, Caitlin E. Mills, Sarah A. Boswell, Xiaoxi Liu et autres

Deubiquitinating enzymes (DUBs), ~100 of which are found in human cells, are proteases that remove ubiquitin conjugates from proteins, thereby regulating protein turnover. They are involved in a wide range of cellular activities and are emerging therapeutic targets for cancer and other …

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Author response: Integrating multi-omics data reveals function and therapeutic potential of deubiquitinating enzymes

Laura M. Doherty, Caitlin E. Mills, Sarah A. Boswell, Xiaoxi Liu et autres

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Inhibition of the deubiquitinating enzyme USP47 as a novel targeted therapy for hematologic malignancies expressing mutant EZH2

Jing Chun Yang, Ellen Weisberg, Shuang Qi, Wei Ni et autres

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Integrating multi-omics data reveals function and therapeutic potential of deubiquitinating enzymes

Laura M. Doherty, Caitlin E. Mills, Sarah A. Boswell, Xiaoxi Liu et autres

ABSTRACT Deubiquitinating enzymes (DUBs) are proteases that remove ubiquitin conjugates from proteins, thereby regulating protein turnover. Inhibition of DUBs promises to make classically undruggable targets such as the tumor suppressor TP53 and oncogene c-Myc amenable to regulation by small molecules. However, the …

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Small molecule inhibition of deubiquitinating enzyme JOSD1 as a novel targeted therapy for leukemias with mutant JAK2

Jing Chun Yang, Ellen Weisberg, Xiaoxi Liu, Robert S. Magin et autres

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B 12 -Mediated, Long Wavelength Photopolymerization of Hydrogels

Robert Mason Hughes, Jennifer R. Shell, David S. Lawrence, Alexander M. Brugh et autres

Medical hydrogel applications have expanded rapidly over the past decade. Implantation in patients by non-invasive injection is preferred, but this requires hydrogel solidification from a low viscosity solution to occur in vivo via an applied stimuli. Transdermal photo-crosslinking of acrylated biopolymers with …