Kenian Chen
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View article: A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution
A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution Open
Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscl…
View article: Actinomycin D and bortezomib disrupt protein homeostasis in Wilms tumor
Actinomycin D and bortezomib disrupt protein homeostasis in Wilms tumor Open
Wilms tumor is the most common kidney cancer in children, and diffuse anaplastic Wilms tumor is the most chemoresistant histological subtype. Here, we explore how Wilms tumor cells evade the common chemotherapeutic drug actinomycin D, whic…
View article: A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response
A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response Open
We present an integrated single-cell RNA sequencing atlas of the primary breast tumor microenvironment (TME) containing 236,363 cells from 119 biopsy samples across eight datasets. In this study, we leverage this resource for multiple anal…
View article: Coactivator condensation drives cardiovascular cell lineage specification
Coactivator condensation drives cardiovascular cell lineage specification Open
During development, cells make switch-like decisions to activate new gene programs specifying cell lineage. The mechanisms underlying these decisive choices remain unclear. Here, we show that the cardiovascular transcriptional coactivator …
View article: A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer
A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer Open
There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent …
View article: CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway
CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway Open
Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high-grad…
View article: CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model
CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model Open
Cardiovascular diseases are the most common cause of worldwide morbidity and mortality, highlighting the necessity for advanced therapeutic strategies. Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is a prominent inducer of variou…
View article: Elimination of CaMKIIδ Autophosphorylation by CRISPR-Cas9 Base Editing Improves Survival and Cardiac Function in Heart Failure in Mice
Elimination of CaMKIIδ Autophosphorylation by CRISPR-Cas9 Base Editing Improves Survival and Cardiac Function in Heart Failure in Mice Open
BACKGROUND: Cardiovascular diseases are the main cause of worldwide morbidity and mortality, highlighting the need for new therapeutic strategies. Autophosphorylation and subsequent overactivation of the cardiac stress-responsive enzyme Ca…
View article: Comparison of different surgical treatments for stage II progressive collapsing foot deformity deformity-A Finite element analysis
Comparison of different surgical treatments for stage II progressive collapsing foot deformity deformity-A Finite element analysis Open
Background: This study analyzed the advantages and disadvantages of different procedures for stage IIA progressive collapsing foot deformity (PCFD) through three-dimensional finite element models. Methods: Medial column fusion (MCF), media…
View article: Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy
Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy Open
Mutations in genes encoding nuclear envelope proteins lead to diseases known as nuclear envelopathies, characterized by skeletal muscle and heart abnormalities, such as Emery-Dreifuss muscular dystrophy (EDMD). The tissue-specific role of …
View article: The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma
The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma Open
Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that causes significant devastation, with no effective therapy for relapsed disease. The mechanisms behind treatment failures are poorly understood. Our study showed that treatment …
View article: TWIST2-mediated chromatin remodeling promotes fusion-negative rhabdomyosarcoma
TWIST2-mediated chromatin remodeling promotes fusion-negative rhabdomyosarcoma Open
Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in children that resembles developing skeletal muscle. Unlike normal muscle cells, RMS cells fail to differentiate despite expression of the myogenic determination protein MYOD. The TW…
View article: Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease
Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease Open
CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardio…
View article: Precise genomic editing of pathogenic mutations in <i>RBM20</i> rescues dilated cardiomyopathy
Precise genomic editing of pathogenic mutations in <i>RBM20</i> rescues dilated cardiomyopathy Open
Mutations in RNA binding motif protein 20 ( RBM20 ) are a common cause of familial dilated cardiomyopathy (DCM). Many RBM20 mutations cluster within an arginine/serine-rich (RS-rich) domain, which mediates nuclear localization. These mutat…
View article: 993 InteractPrint predicts clinically meaningful interactions between cancer epithelial cells and immune cells: lessons from a single-cell breast cancer atlas
993 InteractPrint predicts clinically meaningful interactions between cancer epithelial cells and immune cells: lessons from a single-cell breast cancer atlas Open
Background While immunotherapy has revolutionized the treatment of many solid tumors, the efficacy of immunotherapy regimens is comparatively lower in breast cancer. Immunotherapy efficacy is often negatively correlated with intratumor het…
View article: The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma
The MYC-YBX1 Circuit in Maintaining Stem-like Vincristine-Resistant Cells in Rhabdomyosarcoma Open
Rhabdomyosarcoma (RMS) is a devastating pediatric soft tissue sarcoma with no effective therapy for relapsed disease. There is limited knowledge on the mechanisms underlying treatment failures. We demonstrated that treatment of RMS cells w…
View article: Blocking LAIR1 signaling in immune cells inhibits tumor development
Blocking LAIR1 signaling in immune cells inhibits tumor development Open
The current immune checkpoint blockade therapy has been successful in treating some cancers but not others. New molecular targets and therapeutic approaches of cancer immunology need to be identified. Leukocyte associated immunoglobulin li…
View article: A comprehensive single-cell breast tumor atlas defines cancer epithelial and immune cell heterogeneity and interactions predicting anti-PD-1 therapy response
A comprehensive single-cell breast tumor atlas defines cancer epithelial and immune cell heterogeneity and interactions predicting anti-PD-1 therapy response Open
We present an integrated single-cell RNA-seq resource of the breast tumor microenvironment consisting of 236,363 cells from 119 biopsy samples across 8 publicly available datasets. In this computational study, we first leverage this novel …
View article: Plasma Cell Fate Is Orchestrated by Elaborate Changes in Genome Compartmentalization and Inter-chromosomal Hubs
Plasma Cell Fate Is Orchestrated by Elaborate Changes in Genome Compartmentalization and Inter-chromosomal Hubs Open
(Cell Reports 31, 107470-1–107470-15.e1–e6; April 7, 2020) In the originally published version of this article, the description of results presented in Figure 4B was incorrect. In the text, we referred incorrectly to Bcl6 rather than Prdm1…
View article: Plasma Cell Fate Is Orchestrated by Elaborate Changes in Genome Compartmentalization and Inter-chromosomal Hubs
Plasma Cell Fate Is Orchestrated by Elaborate Changes in Genome Compartmentalization and Inter-chromosomal Hubs Open
The transition from the follicular B to the plasma cell stage is associated with large-scale changes in cell morphology. Here, we examine whether plasma cell development is also associated with changes in nuclear architecture. We find that…