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Hilton, L.

Publications and source records attributed to Hilton, L..

3 recordsLinked to original sources

A patient derived xenograft repository capturing clinical and molecular heterogeneity of large B-cell lymphoma

Large B-cell lymphomas (LBCLs) are a clinically and molecularly diverse group of malignancies with a rapidly evolving therapeutic landscape that has introduced new areas of clinical need such as post-CD19 chimeric antigen receptor T (CART19) progression. Patient derived xenograft (PDX) models are an important tool for mechanistic studies and preclinical evaluation of new therapies and can be generated from a variety of clinical contexts that capture tumor-intrinsic resistance mechanisms. We therefore undertook a comprehensive effort to generate PDX models that encompass the molecular landscape of LBCLs and include important clinical scenarios for new drug development. Here we describe the first 48 models within this publicly available repository, capturing the transcriptional and genetic subsets of LBCL. These models also include 23 generated from post-CART progression biopsies which reproduce patterns of progression driven by CD19 mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validate in vivo. STATEMENT OF SIGNIFICANCEYang et al. describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of large B-cell lymphoma. X-LYMPH includes models of chimeric antigen receptor T cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas.

cancer biology↗

Could instructor talk drive CURE effectiveness? A comparative study of instructor talk in introductory lab courses

Course-based undergraduate research experiences (CUREs) are thought to enhance students motivation to continue in college, in science, and in research. Yet, how CUREs enhance student motivation is largely undefined. Theories of instructor immediacy, self-efficacy, and task values suggest that CURE instructors may talk in ways that influence students motivational beliefs. We characterized the non-content related talk of instructors teaching 48 introductory biology lab courses, half CUREs and half non-CUREs. We identified 14 types of instructor talk that fit these theoretical perspectives: fostering students closeness with their instructor (i.e., immediacy talk), building students confidence in their scientific abilities (i.e., self-efficacy talk), and promoting students sense of worth in their work (i.e., task value talk). Course type had a medium effect on talk type, with CURE instructors utilizing more immediacy, self-efficacy, and task values talk than non-CURE instructors but also showing more variation in these types of talk. Our results suggest that motivation-related instructor talk is more prevalent in CUREs than non-CUREs, but wide variation in CURE instructor talk indicates additional investigation is needed before non-content talk can be considered a mechanism for the motivational influences of CUREs. HIGHLIGHTThis study compares non-content instructor talk in CURE and non-CURE lab courses using immediacy, self-efficacy, and task value theories. CURE instructors use more talk than non-CURE instructors, but variation in CURE instructor talk leaves open the question of whether talk is a causal factor in the motivational influence of CURE instruction.

scientific communication and education↗

Multidimensional characterization of cellular ecosystems in Hodgkin lymphoma

The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that co-evolve with a complex ecosystem of immune cells in the tumor microenvironment (TME). The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogeneity and clinically relevant molecular subtypes. Here, we employed an integrative, multimodal approach to characterize CHL tumors using malignant cell sequencing, spatial transcriptomics and imaging mass cytometry. We identified four molecular subtypes (CST, CN913, STB, and CN2P), each characterized by distinct clinical features, mutational patterns, malignant cell gene expression profiles, and spatial architecture involving immune cell populations. Functional modeling of CSF2RB mutations, a characteristic feature of the CST subtype, revealed dysregulated oncogenic signaling and unique TME crosstalk. These findings highlight the significance of multi-dimensional profiling in elucidating patterns of molecular alterations that drive immune ecosystems and underlie therapeutically exploitable vulnerabilities.

cancer biology↗